ANTI-MCT1 ANTIBODIES AND THEIR USES

Abstract

This invention generally relates to antibodies and antigen-binding fragments thereof, for example, humanized, chimeric, and human antibodies and antigen-binding fragments thereof, and fusion proteins, compositions containing such antibodies and antigen-binding fragments thereof and fusion proteins, wherein such antibodies and antigen-binding fragments thereof and fusion proteins specifically bind to MCT1, for example, human or non-human MCT1 and antagonize, inhibit, or block one or more MCT1-associated functions in vitro and / or in vivo.The invention also relates to therapeutic and diagnostic uses of these anti-MCT1 antibodies, antigen-binding fragments, fusion proteins, and compositions containing them, where these anti-MCT1 antibodies, antigen-binding fragments, fusion proteins, and compositions containing them are used in therapeutic regimens that further include the administration of other therapeutic agents, for example, mitochondrial inhibitors and / or biguanides or small molecule MCT1 inhibitors.

Description

ANTI-MCT1 ANTIBODIES AND THEIR USES RELATED REQUESTS This application claims priority to US Provisional No. 62 / 613,447 filed on January 4, 2018, US Provisional No. 62 / 684,870 filed on June 14, 2018, and US Provisional No. 62 / 736,025 filed on September 25, 2018 and US Provisional No. 62 / 773,630 filed on November 30, 2018. The content of each of these provisional applications is incorporated by reference in its entirety herein. LIST OF SEQUENCES The sequence listing in the file named 43260.4213.txt having a size of xxxxxx bytes that was created on January 4, 2019, is incorporated herein by reference in its entirety. FIELD OF THE INVENTION This invention generally relates to anti-MCT1 antibodies and antigen-binding fragments thereof, eg, humanized, chimeric, and human antibodies and antigen-binding fragments thereof, eg, antagonistic anti-MCT1 antibodies and antigen-binding fragments thereof. antigen thereof, and compositions containing such antibodies and antigen-binding fragments thereof. Such antigen-binding antibodies and fragments include those that specifically bind to MCT1, for example, MCT1 expressed on the surface of endogenous human cells that express MCT1 or recombinant cells engineered to express MCT1 and that antagonize one or more associated functions. with MCT1, for example, its ability to promote lactate transport. The invention also relates to multispecific or fusion proteins comprising one or more anti-MCT1 antibody binding sequences, eg, multispecific and bispecific antibodies. The invention further relates to therapeutic and diagnostic uses for such antibodies, antigen-binding fragments, multispecific and fusion polypeptides, and compositions containing the same. The invention specifically relates to the use of these antibodies and antigen-binding fragments thereof as prophylactics or treatments, for example, for the treatment of autoimmunity, inflammation, allergy, transplantation, GVHD, cancer, and other conditions where suppression of the MCT1 activity and / or increased number / activity of TR1 lymphocytes and / or decreased number / activity of effector T lymphocytes are therapeutically desirable. BACKGROUND OF THE INVENTION The monocarboxylate nutrient transporter SLC16A1 (MCT1) is a multipass transmembrane protein responsible for the facilitated transport of key metabolites, including products of glycolysis. MCT1 is a member of one of the largest families of surface membrane proteins, known as solute channel (SLC) proteins, whose functions involve the transport across zncRan / nznz / q / YiAi membranes of critical cellular nutrients, metabolites, ions, hormones and lipids. MCT1 belongs to the SLC16 family of transporters, five of which have been shown to transport monocarboxylates, such as pyruvate, lactate, and ketones (REF. 34-36) in a facilitated, pH-dependent, and bidirectional manner. SLC16A1 (MCT1), SLC16A7 (MCT2), SLC16A8 (MCT3) and SLC16A3 (MCT4) have been shown to transport monocarboxylates with Km in the range of 1-40 mM (REF. 37). MCT1, MCT3 and MCT4 are co-expressed with the Ig domain containing surface protein CD147 (Basigin), which in many cells is critical for proper cell surface expression (REF. 38, 37). In addition to these MCTs, other lactate transporters include the recently characterized SLC16A11 (REF. 39) and sodium-dependent SLC5A8 and SLC5A12 (REF. 40), AQP9 (REF. 41, 42) as well as SLC4A1 (Land 3) expressed in red blood cells. reds. Thus, nine independent proteins can control and regulate lactate transport into, between, and out of cells throughout the body. MCT1 is especially relevant for lactate transport in T and B lymphocytes (REF. 43). Immune cells undergo changes in their metabolic demand during growth and require specific metabolic states to employ their effector functions. Blocking glycolysis in models of inflammatory diseases has shown efficacy (REF. 53). For example, the development of lupus in mice prone to the disease is prevented when lymphocytes are blocked from using the glycolytic pathway after activation (REF. 53). In fact, the lack of IFNγ production in these models is consistent with previous reports that have shown that glycolysis is required for IFNγ production (REF. 54). Blocking lactate export reduces flux through the glycolytic pathway (REF. 55) and, by disrupting Myc, may divert T cells from effector functions (REF. 56). Inhibition of MCT1 function blocks effector T cell activity in several animal models of disease, including collagen-induced arthritis, allograft rejection, and GVHD (REF. 45, 47, 50, 57-59). However, the ubiquity of these pathways in non-immune cells and the lack of immunospecific targets have prevented therapeutic intervention. Given the wide expression of MCTs in many tissues, small molecule approaches that affect multiple MCTs pose particular challenges including tissue toxicities. For example, AZ3965 is a small molecule that binds to MCT1 and MCT2 (REF. 45, 46). This small molecule MCT1 / 2 inhibitor had potential applications in the treatment of autoimmune diseases / transplantation (REF. 47), but promiscuous binding produced toxicities to the retina, heart, and testes in preclinical models (REF. 48, 85). . Adult humans deficient in MCT1 are healthy (REF. 49, 68). Individuals with homozygous MCT1 loss-of-function (LOF) mutations were identified only under stress (infection, starvation) due to alterations in ketone utilization and metabolism. Babies have defective ketone utilization and sometimes exercise intolerance. These various symptoms disappeared as they aged, possibly due to growth in skeletal muscle mass during adolescence. Heterozygous relatives of individuals with homozygous MCT1 mutations had no history of ketoacidosis, suggesting that zncRan / nznz / q / Yi LOF mutations cause ketoacidosis only in conjunction with additional genetic / environmental factors (REF. 68). Outside of the immune system, MCT1 is expressed in multiple organs, including skeletal muscle, kidney, liver, testes, heart, and brain, along with other MCTs. The lack of widespread toxicity in individuals with MCT1 mutations is probably due to the high redundancy of MCT. For example, MCT1, MCT2, and MCT4 are expressed in the retina (REF. 69), and no retinal defects were observed in MCT1-deficient individuals, suggesting functional redundancy. At this time, overt immune deficiencies have not been observed in individuals with MCT1 deficiency. In addition, MCT1-deficient humans do not have RBC dysfunction. There are metabolic differences between cancer cells and normal cells: in particular, tumor cells rely on a high rate of aerobic glycolysis rather than oxidative phosphorylation to produce energy for the maintenance of cellular functions. In fact, cancer cells have up to a 60-fold increased rate of glycolysis relative to normal cells, even with sufficient oxygen. This dependence on glycolysis and its consequences is called the Warburg effect (REF. 94, 95). Malignant cells are highly anabolic and require very high levels of nutrients, ATP, and building blocks to synthesize the components necessary for their growth and survival. Use of the glycolytic pathway provides ATP but also drives the production of lactate, which is produced from pyruvate at the end of the glycolytic pathway. The massive production of lactate by the tumor cell requires an efficient means for its consumption or elimination, to prevent intracellular acidification of the cancer cell. One of the ways that lactate homeostasis is maintained is through monocarboxylate transporters. Expression profiling studies have established that the most aggressive tumor types express markedly elevated levels of MCT1, MCT4, or both (REF. 96). The expression of MCT1 and MCT4 is regulated by two major oncogenic transcription factors, MYC and hypoxia-inducible factor-1a (HIF-1a), respectively (REF. 96, 97) that markedly increase the production of key proteins that support the aerobic glycolysis, including amino acid transporters and enzymes involved in glutamine and glucose catabolism (REF. 98). MYC-involved malignancies and hypoxic tumors are generally resistant to current first-line therapies, with high rates of treatment failure, relapse, and high patient mortality (REF. 99, 100). Importantly, MCT1 inhibition can kill tumor cells ex vivo and cause tumor regression in vivo, and its potency is enhanced by agents such as metformin that force a glycolytic phenotype on the cancer cell (REF. 96,100). MCT1 is normally expressed at very low levels in pancreatic islets and in beta cells in particular (REF. 101, 102). This probably explains the very slow uptake of lactate by these cells. A hallmark of exercise-induced hyperinsulinism (EIHI) is inappropriate insulin secretion after vigorous physical activity, leading to hypoglycemia (REF. 103). EIHI has been associated with elevated expression of MCT1 in beta cells and transgenic mice engineered to overexpress MCT1 in part exhibited many of the zncRan / nznz / q / Yi features of EIHI (REF. 104). As described above, several small molecule MCT inhibitors have been developed, but many of these small molecule inhibitors lack specificity for MCT1, thus leading to secondary target toxicities. Despite these drawbacks, small molecule MCT1 inhibitors have been shown to disable tumor cell metabolism, proliferation, and survival, and to impair the tumorigenic potential in vivo in highly expressed MCT1-expressing tumors (REF. 96 ). The antitumor effects of such small-molecule MCT1 inhibitors are increased by co-administration of the biguanide metformin, which is believed to further increase the reliance of tumor cells on aerobic glycolysis and thus increase the demand for blood flow. MCT1-mediated lactate (REF. 96). However, antibodies that bind to surface-expressed MCT1, eg, those that bind to surface-expressed MCT1 of human or non-human cells expressing endogenous or engineered MCT1, have not been reported so far. Furthermore, to Applicants' knowledge, no functional antibodies have been reported in the literature, ie, those that bind to MCT1 and thus antagonize, inhibit or block the effects of MCT1. BRIEF DESCRIPTION OF THE INVENTION For the first time, this invention provides antibodies and antigen-binding fragments thereof that specifically bind to human MCT1 expressed on the surface of cells expressing endogenous or recombinant MCT1, eg, human cells whose antibodies are also functional, ie, such antibodies antagonize MCT1-related functions. More specifically, the invention provides novel antibodies and antigen-binding fragments thereof that specifically bind to human MCT1 that antagonize MCT1-related functions such as inhibiting MCT1-mediated lactate transport. The invention further provides MCT1-binding fusion proteins and multispecific MCT1-binding polypeptides comprising one or more MCT1-binding antibody variable domains and optionally other portions, for example, another polypeptide such as another antigen-binding variable domain. , cytokine or a receptor. The invention further provides an isolated antibody or antigen-binding fragment thereof that binds to one or more residues comprised in an extracellular domain or region of human or non-human MCT1. The invention further provides an isolated antibody or antigen-binding fragment thereof that binds to human or non-human MCT1 that antagonizes, inhibits, or blocks one or more MCT1-related functions, eg, in vitro and / or in vivo. The invention further provides an isolated antibody or antigen-binding fragment that binds to a non-human, eg, rodent, MCT1 such as mouse or rat MCT1, which optionally antagonizes, inhibits, or blocks one or more MCT1-related functions, by example, in vitro and / or in vivo, eg, which optionally further binds to human MCT1. zncRan / nznz / q / Yi The invention further provides an isolated anti-MCT1 antibody or an antigen-binding fragment thereof that competes for binding to human or non-human MCT1 such as any of the Ab1-Ab95 antibodies to human MCT1. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof that bind to the same or overlapping epitope on human MCT1 as any of the Ab1-Ab95 human anti-MCT1 antibodies. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof that bind to an epitope on human MCT1 selected from the following: (i) one comprising one or more of residues T41, E46, S285, S286, Y287, K289, H292, Y293, K297, G417, I47 and D418; (ii) one comprising at least three residues wherein at least one, two or all three of said residues comprise a residue selected from T41, E46, S285, S286, Y287, K289, H292, Y293, G417, I47 and D418 ; (iii) one comprising three residues wherein three residues wherein at least one, two or all three of said residues comprise T41, E46, S285, S286, Y287, K289, H292, Y293, G417, I47 and D418; (iv) one comprising three to six residues wherein one, two, three, four, five or six of said residues comprise T41, E46, S285, S286, Y287, K289, H292, Y293, G417, I47 and D418; (v) one comprising at least one, two or all three residues T41, S285 and S286; (vi) one comprising T41; (vii) one comprising S286; (viii) one comprising S285; (ix) one comprising H292; (x) one comprising residues T41, S285, S286, Y287, G417 and D418; (x¡) one comprising residues T41, S285 and S286; (xii) one comprising residues T41, I47, S285, S286, G417 and D418, (xiii) one comprising residues E46, K289 and H292; (xiv) one comprising residues K297, Y293 and H292; (xv) one comprising one or more residues corresponding to a non-human MCT1, eg selected from rodent (eg mouse, rat, guinea pig), rabbit, chicken, non-human primate (eg Macaca fascicularis, chimpanzee, orangutan), cattle, sheep, canines and cats; wherein optionally residues present in said epitope are identified by use of alanine scanning. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof that bind to an epitope on selected human MCT1 according to claim 7, wherein said antibody or antigen-binding fragment further interacts with zncRan / nznz / q / Yi one or more of the following residues: (i) one or more of residues P37, I40, K45, E48 and T55 (loop 1); (ii) residue Q111 (loop 2); (iii) residue Q166 (loop 3); (iv) one or more of residues L284, E296, S298 (loop 4); (v) residue Y353 (loop 5); (vi) one or both residues Y419, T422 (loop 6); and / or (vii) any combination of the above. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof that bind to an epitope on non-human MCT1, wherein said non-human MCT1 is optionally selected from rodent (eg mouse, rat, guinea pig), rabbit , bird (eg chicken, turkey, goose), non-human primate (eg Macaca fascicularis, chimpanzee, orangutan), bovine, ovine, canine, feline, optionally wherein said epitope on non-human MCT1 comprises one or more of corresponding residues in the non-human MCT1 such as one or more of human MCT1 T41, S285, S286, Y287, G417, I47 and D418, for example, which antagonize, inhibit or block one or more of the activities of said non-human MCT1 eg, in vitro and / or in vivo. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof that are human, humanized, non-human primate, primatized, chicken, rodent, or chimeric. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof which inhibit human MCT1-mediated lactate transport, eg, in vitro and / or in vivo. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof which bind to endogenous MCT1-expressing cells and / or bind to engineered or recombinant MCT1-expressing cells eg, MCT1-expressing 293 cells human. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof wherein the antibody or antigen-binding fragment thereof is selected from the group consisting of: a human or humanized monoclonal antibody; monospecific antibody; polyspecific antibody; a multispecific antibody-like polypeptide, a humanized antibody; a human or humanized tetrameric antibody; a human or humanized tetravalent antibody; a human or humanized multispecific antibody; a single chain antibody; a domain specific antibody; a single domain antibody; a domain deleted antibody; an scFc fusion protein; a chimeric antibody; a synthetic antibody; a recombinant antibody; a hybrid antibody; multispecific antibody, bispecific antibody, ByTE, a mutated antibody; CDR-grafted antibodies; an antibody fragment; a Fab; an F(ab')2; a Fab' fragment; an Fv fragment; a single chain Fv fragment (scFv); an Fd fragment; a dAb fragment; diabodies; a nanobody; a bivalent nanobody; a VHH antibody; and a minibody. zncRan / nznz / q / Yi The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof comprising humanized antibodies or antigen-binding fragments thereof. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof comprising at least 1, 2, 3, 4, 5 or all 6 CDRs of any of the anti-MCT1 antibodies Ab1-Ab95, wherein optionally said CDRs are defined according to Kabat or according to Chothia and Lesk, or an isolated antibody or antigen-binding fragment thereof that competes for binding to MCT1 or binds to the same epitope with any of the anti-MCT1 antibodies Ab1 - Ab95 or an affinity matured variant of any of the above. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof that are humanized comprising the same CDRs as any of the anti-MCT1 Ab1-Ab95 antibodies, where optionally said CDRs are defined according to Kabat or according to according to Chothia and Lesk. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof comprising the same VH polypeptide that is comprised in an anti-MCT1 antibody selected from Ab1-Ab95 or a humanized variant thereof. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof comprising the same VL polypeptide that is comprised in an anti-MCT1 antibody selected from Ab1-Ab95 or a humanized variant thereof. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof comprising a VH polypeptide and a VL polypeptide that are identical to those comprised in an anti-MCT1 antibody selected from Ab1-Ab95 or a humanized variant thereof. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof comprising a variable heavy polypeptide and / or a variable light chain polypeptide respectively possessing at least 80, 90, 95, 96, 97, 98, 99 or 100% sequence identity with a variable heavy polypeptide and / or a variable light chain polypeptide contained in any of the Ab1-Ab95 anti-MCT1 antibodies. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof comprising VH CDR1, 2 and 3 polypeptides respectively having the amino acid sequences of SEQ ID NO: 4-6 and VL CDR1, 2 and VL polypeptides. 3 respectively having the amino acid sequences of SEQ ID NO: 7-9. The invention further provides isolated anti-MCT1 antibodies or antigen-binding fragments thereof which is a humanized anti-MCT1 antibody or antigen-binding fragment derived from any of Ab1-Ab95, optionally containing the same CDRs as any of Ab1- Ab95, wherein optionally said CDRs are defined according to Kabat or according to Chothia and Lesk. The invention further provides affinity matured anti-MCT1 antibodies or antigen-binding zncRan / nznz / q / Yi fragments derived from any of Ab1-Ab95, wherein at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 CDR residues are mutated relative to CDR residues that are comprised in the 6 CDR polypeptides of any one of Ab1-Ab95, wherein optionally said affinity-matured anti-MCT1 antibody binds a human MCT1 with at least the same or greater affinity than the anti-MCT1 antibody from which it is derived and / or the antigen-binding fragment or affinity-matured antibody antagonizes human MCT1, eg, in vitro and / or in vivo, wherein optionally said CDRs are defined according to Kabat or according to Chothia and Lesk optionally wherein at most 1,2, 3, 4, 5, 6 or 7 CDR residues are mutated relative to the CDR polypeptides of any one of Ab1-Ab95 or at most 1, 2, 3 or 4 CDR residues are mutated relative to c with the CDR polypeptides of any of Ab1-Ab95 or at most 1 or 2 CDR residues are mutated relative to the CDR polypeptides of any of Ab1-Ab95. The invention further provides an anti-human MCT1 antibody or an antigen-binding fragment according to any of the foregoing, which further binds to a non-human MCT1, optionally rodent, rabbit, chicken or non-human primate MCT1. The invention further provides anti-MCT1 antibodies comprising the VH and VL polypeptides of SEQ ID NO: 2 and 3; SEQ ID NO: 12 and 13; SEQ ID NO: 14 and 15; SEQ ID NO: 16 and 17; or one comprising the VL and / or VH polypeptides of any of the Ab5-Ab95 antibodies, or comprising humanized or affinity matured variants of the VL and / or VH polypeptides of any of the Ab5-Ab95 antibodies. The invention further provides anti-MCT1 antibodies or antigen-binding fragments comprising a variable heavy chain polypeptide or a heavy chain polypeptide having an amino acid sequence selected from SEQ ID NO: 2, 12, 14, 16, 19- 32, 45, 47, 49, 51,53, 55, 57, 59, 61, 63, 65, 67, 69, 71,73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153 and 155: and a variable light chain polypeptide or light chain polypeptide having an amino acid sequence selected from SEQ ID NO: 3, 13, 15, 17, 33-44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154 and 156. The invention further provides anti-MCT1 antibodies or antigen-binding fragments comprising a variable heavy chain polypeptide and a variable light chain polypeptide having an amino acid sequence selected respectively from the following: SEQ ID NO: 2 and 3; SEQ ID NO: 12 and 13; SEQ ID NO: 14 and 15; SEQ ID NO: 16 and 17; SEQ ID NO: 45 and 46; SEQ ID NO: 47 and 48; SEQ ID NO: 49 and 50; SEQ ID NO: 51 and 52; SEQ ID NO: 53 and 54; SEQ ID NO: 55 and 56; SEQ ID NO: 57 and 58; SEQ ID NO: 59 and 60; SEQ ID NO: 61 and 62; SEQ ID NO: 63 and 64; SEQ ID NO: 65 and 66; SEQ ID NO: 67 and 68; SEQ ID NO: 69 and 70; SEQ ID NO: 71 and 72; SEQ ID NO: 73 and 74; SEQ ID NO: 75 and 76; SEQ ID NO: 77 and 78; SEQ ID NO: 79 and 80; SEQ ID NO: 81 and 82; SEQ ID NO: 83 and 84; SEQ ID NO: 85 and 86; SEQ ID NO: 87 and 88; SEQ ID NO: 89 and 90; SEQ ID NO: 91 and 92; SEQ ID NO: 93 and 94; SEQ ID NO: 95 and 96; zncRan / nznz / q / Yi SEQ ID NO: 97 and 98; SEQ ID NO: 99 and 100; SEQ ID NO: 101 and 102; SEQ ID NO: 103 and 104; SEO ID NO: 105 and 106; SEQ ID NO: 107 and 108; SEQ ID NO: 109 and 110; SEQ ID NO: 111 and 112; SEQ ID NO: 113 and 114; SEQ ID NO: 115 and 116; SEQ ID NO: 117 and 118; SEQ ID NO: 119 and 120; SEQ ID NO: 121 and 122; SEQ ID NO: 123 and 124; SEQ ID NO: 125 and 126; SEQ ID NO: 127 and 128; SEQ ID NO: 129 and 130; SEQ ID NO: 131 and 132; SEQ ID NO: 133 and 134; SEQ ID NO: 135 and 136; SEQ ID NO: 137 and 138; SEQ ID NO: 139 and 140; SEQ ID NO: 141 and 142; SEQ ID NO: 143 and 144; SEQ ID NO: 145 and 146; SEQ ID NO: 147 and 148; SEQ ID NO: 149 and 150; SEQ ID NO: 151 and 152; SEQ ID NO: 153 and 154 and SEQ ID NO: 155 and 156. The invention further provides humanized and / or affinity matured anti-MCT1 antibodies or antigen-binding fragments according to any of the above embodiments comprising a VL polypeptide having an amino acid sequence selected from those of SEQ ID NO: 3, 13, 15, 17 and 33-44 or that of any of the Ab5-Ab60 antibodies. The invention further provides humanized anti-MCT1 antibodies or antigen-binding fragments according to any of the above embodiments comprising a VH polypeptide having an amino acid sequence selected from those of SEQ ID NO: 2, 12, 14, 16 and 19-32 or that of any of the Ab5-Ab60 antibodies. The invention further provides humanized anti-MCT1 antibodies or antigen-binding fragments according to any of the foregoing comprising a VL polypeptide having an amino acid sequence selected from SEQ ID NO: 13, 15, 17 and 33-44 and a VH polypeptide having an amino acid sequence selected from those of SEQ ID NO: 12, 14, 16 and 19-32 or that of any of the Ab5-Ab60 antibodies. The invention further provides humanized anti-MCT1 antibodies or antigen-binding fragments according to any of the foregoing comprising a VL polypeptide having a sequence that is at least 80, 85, 90, 95, 96, 97, 98 or 99 % sequence identity for any of SEQ ID NO: 3, 13, 15, 17, 33-44 or for a VL polypeptide comprised in any of the Ab5-Ab95 antibodies. The invention further provides humanized anti-MCT1 antibodies or antigen-binding fragments according to any of the foregoing comprising a VH polypeptide having a sequence that is at least 80, 85, 90, 95, 96, 97, 98, 99 % or 100% sequence identity with any of SEQ ID NO: 2, 12, 14, 16, 19-32 or with a VH polypeptide comprised in any of the Ab5-Ab95 antibodies. The invention further provides humanized anti-MCT1 antibodies or antigen-binding fragment according to any of the foregoing comprising a VL polypeptide having a sequence possessing at least 80, 85, 90, 95, 96, 97, 98 or 99 % sequence identity to any of SEQ ID NO: 3, 13, 15, 17, 33-44 or to a VL polypeptide comprised of any of the Ab5-Ab95 antibodies and / or a VH polypeptide having a sequence having at least 90, 95, 96, 97, 98, 99% or 100% sequence identity with the VH polypeptide of SEQ ID NO: 2, 12, 14, 16, 19-32 or with a VH polypeptide comprised in any of the Ab5-Ab95 antibodies. The invention further provides a humanized anti-MCT1 antibody or an antigen-binding zncRan / nznz / q / Yi fragment according to any of the above, wherein the heavy chain CDR3 sequence comprises 18, 19, 20, 21, 22 , 23 or 24 amino acid residues. The invention further provides a humanized anti-MCT1 antibody or antigen-binding fragment according to any of the foregoing, wherein the heavy chain CDR3 sequence comprises 21, 22, 23 or 24 amino acid residues. The invention further provides an anti-MCT1 human or antigen-binding fragment isolated according to any of the above, wherein the heavy chain CDR3 sequence is identical to or differs from SEQ ID NO: 6 by a maximum of 5, 4, 3, 2 or 1 residues, optionally wherein said differences, if present, comprise conservative amino acid substitutions or comprise prevailing substituent amino acids at the same position in the heavy chain CDR3 of human or rodent antibodies comprising a CDR3 of the same length. The invention further provides an isolated human or humanized anti-MCT1 antibody or antigen-binding fragment thereof according to any of the foregoing that competes for binding to MCT1 with a reference antibody, wherein the reference antibody is selected from Ab1-Ab95. The invention further provides human anti-MCT1 antibodies or antigen-binding fragments thereof comprising the same variable heavy and / or light CDR polypeptides as an anti-human MCT1 antibody selected from Ab1-Ab95. The invention further provides anti-MCT1 antibodies comprising the variable heavy and / or light polypeptides of an antibody selected from Ab1-Ab95. The invention further provides human or humanized anti-MCT1 antibodies or antigen-binding fragments thereof according to any of the foregoing, comprising heavy and / or light chain constant regions, optionally heavy and / or light chain constant regions human lgG1, lgG2, lgG3 or lgG4 whose constant regions are optionally mulated to impair or enhance at least one effector function, eg, wherein said effector functions include FcR binding, complement binding, ADCC function, FcRN binding and glycosylation . The invention further provides anti-MCT1 antibodies or an antigen-binding fragment thereof according to any of the foregoing, wherein the CDRs of the antibody or antigen-binding fragment thereof form a similar three-dimensional antibody structure that is similar or the same as that of Ab1, as indicated by positions of the alpha carbons in the corresponding CDRs that differ by a root mean square deviation (RMSD) of less than 2.0 Á, less than 1.0 Á, or less than 0.5 Á , as determined by structural alignment. The invention further provides humanized antibodies or antigen-binding fragments thereof comprising the Ab1 variable heavy chain CDR sequences (SEQ ID NOS: 4, 5, 6) and the Ab1 variable light chain CDR sequences (SEQ ID NOS: 7, 8, 9) The invention further provides anti-MCT1 antibodies or antigen-binding fragment thereof comprising a VH domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity to the zncRan / nznz / q / Yi domain amino acid sequence MCT1 Ab1 VH (SEQ ID NO: 2); and comprising a VL domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity with the amino acid sequence of the VL domain of MCT1 Ab1 (SEQ ID NO: 3). The invention further provides anti-MCT1 antibodies or antigen-binding fragment thereof according to any of the above embodiments comprising human constant domains, optionally IgG1, IgG2, IgG3 or IgG4, optionally further modified to enhance at least one function Selected Fe effector of glycosylation, FcR binding, FcRN binding, complement binding, and ADCC function. The invention further provides anti-MCT1 antibodies or an antigen-binding fragment thereof according to any of the above embodiments comprising human IgG1 constant regions, optionally modified to decrease FcR binding and / or complement binding, further optionally comprising E269R and / or K322A mutations and / or said human lgG1 constant regions comprising the amino acid sequence of SEQ ID NO: 18. The invention further provides fusion polypeptides, chimeric antigen receptors (CARs), multispecific antigen-binding polypeptides, or multispecific or bispecific antibody polypeptides comprising at least one anti-MCT1 antibody or antigen-binding fragment according to any of the previous. The invention further provides an anti-MCT1 antibody or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide, or multispecific or bispecific antibody polypeptide of any of the above embodiments that decreases T cell activity. effector cells and / or the number of effector T cells, eg, CD3+, CD4+ or CD8+ effector T cells. The invention further provides anti-MCT1 antibodies or fusion polypeptides, chimeric antigen receptors (CARs), multispecific antigen-binding polypeptides, or multispecific or bispecific antibody polypeptides of any of the above embodiments that increase the activity and / or the number of Tr1 lymphocytes. The invention further provides anti-MCT1 antibodies or fusion polypeptides, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide, or multispecific or bispecific antibody polypeptide of any of the above embodiments that decreases T cell activity. effectors and / or the number of effector T cells, eg, CD3+, CD4+ or CD8+ effector T cells and more, which increases the activity and / or number of Tr1 cells. The invention further provides cells expressing at least one anti-MCT1 antibody or antigen-binding fragment, fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide, or multispecific or bispecific antibody polypeptide according to any of the foregoing, eg human, non-human mammalian cells, yeast, bacteria, amphibian, plant, insect or reptile or a human cell, optionally a human immune cell, eg a T lymphocyte, NK cells, monocytes, lymphocytes T regulators or macrophages. zncRan / nznz / q / Yi The invention further provides anti-idiotypic antibodies raised against an anti-MCT1 antibody or antigen-binding fragment thereof according to any of the foregoing, optionally which is human, humanized and / or affinity matured. The invention further provides anti-anti-idiotypic antibodies raised against an anti-idiotypic antibody as described above that optionally binds to MCT1 and further optionally blocks or antagonizes one or more MCT1 activities. The invention further provides fusion proteins comprising an anti-MCT1 antibody or an antigen-binding fragment thereof according to any of the above or the VH CDR3 polypeptide of SEQ ID NO: 6 or a variant possessing at least 80% of sequence identity therewith, which is directly or indirectly linked to another polypeptide, for example, an antibody polypeptide or antibody domain, serum albumin, human or other primate serum albumin, adnectin, an affibody, a DARPin, an anticalin , glycol (PEG), monomethoxy PEG (mPEG), an XTEN molecule, an rPEG molecule, or fragment or variant of any of the foregoing, for example, wherein the antibody polypeptide or domain comprises an Fe polypeptide or fragment thereof, e.g. example, a human IgG1, IgG2, IgG3 or IgG4 F region or fragment thereof. The invention further provides anti-MCT1 antibodies or antigen-binding fragments thereof or fusion polypeptides, chimeric antigen receptors (CARs), multispecific antigen-binding polypeptides, or multispecific or bispecific antibody polypeptides according to any of the foregoing, or a cell expressing any of the above, which elicits one or more of the following properties upon binding to MCT1 on the surface of a cell, for example, an activated T cell or B cell, also optionally a human cell: (i) inhibits lactate transport; (ii) inhibits the transport of bromopyruvate; (i¡) inhibits the transport of one or more monocarboxylates, pyruvate, branched-chain oxoacids derived from leucine, valine, and isoleucine, ketone bodies, acetoacetate, beta-hydroxybutyrate, acetate, lactic acid, cellular nutrients, metabolites, ions, hormones , lipids, and ketones; (iv) inhibits the proliferation of CD3 / CD28 stimulated T lymphocytes; (v) inhibits the proliferation of activated T lymphocytes or B lymphocytes; (vi) inhibits the production of one or more inflammatory cytokines; (vii) decreases the activity and / or number of effector T cells, eg, CD3+, CD4+ and / or CD8+ effector T cells; (viii) increases the proportion or activity of regulatory T cells (Tregs); (ix) inhibits allogeneic activation in a mixed lymphocyte reaction; (x) or a combination of any of the above. The invention further provides anti-MCT1 antibodies or antigen-binding fragments thereof or fusion polypeptides, chimeric antigen receptors (CARs), multispecific antigen-binding polypeptides, or multispecific or bispecific antibody polypeptides according to zncRan / nznz / q / Yi any of the above, or a cell expressing any of the above, eg, according to any of the above embodiments, which inhibits the production of one or more inflammatory cytokines by binding to MCT1. The invention further provides anti-MCT1 antibodies or antigen-binding fragments thereof or fusion polypeptides, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptides or multispecific or bispecific antibody polypeptides according to any of the forms of embodiments above, or a cell expressing any of the above, wherein at least one of the one or more inflammatory cytokines is selected from FGF2, FLT-3L, Fractalkine, GCSF, GM-CSF, GRO, IFNa2, IFNy, IL- 3, IL-5, IL-9, IL-10, IL-12p40, IL-12p70, IL-13, IL-17a, IP-10, MCP1, MDC, MIP-1a, MIP-1b, sCD40L, TNF and TNFp. The invention further provides anti-MCT1 antibodies or antigen-binding fragments thereof or fusion polypeptides, chimeric antigen receptors (CARs), multispecific antigen-binding polypeptides, or multispecific or bispecific antibody polypeptides according to any of the foregoing, or a cell expressing any of the above, wherein at least one of the one or more inflammatory cytokines is selected from IFNγ, GM-CSF, TNFα, IL-10, and IL-6. The invention further provides anti-MCT1 antibodies or antigen-binding fragments thereof or fusion polypeptides, chimeric antigen receptors (CARs), multispecific antigen-binding polypeptides, or multispecific or bispecific antibody polypeptides according to any of the forms of embodiments above, or a cell expressing any of the above, that inhibits MCT1-mediated lactate transport in activated T cells with a Kd of less than 100 nM, less than 50 nM, or less than 10 nM, as measured by a FLIPR lactate assay. The invention further provides anti-MCT1 antibodies or antigen-binding fragments thereof or fusion polypeptides, chimeric antigen receptors (CARs), multispecific antigen-binding polypeptides, or multispecific or bispecific antibody polypeptides according to any of the foregoing, or a cell that expresses any of the above, that does not: (i) binds to MCT2, MCT3, MCT4 and / or CD147 as measured by flow cytometry; (ii) inhibits the transport of MCT2, MCT3 and / or MCT4; (i¡¡) inhibits the production of IL-2; (iv) inhibits lactate transport in monocytes; (v) inhibits the proliferation of naïve, resting and / or regulatory T lymphocytes; (vi) inhibits lactate transport in RBCs; (vii) alters the expression of one or more T cell activation markers, optionally selected from CD25, CD54, CD69, CD95, CD98, CD147, CD154, CD278, CD279 and HLA-DR / DP / DQ. The invention further provides anti-MCT1 antibodies or antigen-binding fragments thereof or fusion polypeptides, chimeric antigen receptors (CARs), multispecific antigen-binding polypeptides, or multispecific or bispecific antibody polypeptides according to any of the foregoing, or a cell expressing any of the above, comprising a zncRan / nznz / q / Yi Fe region of human lgG1, lgG2, lgG3 or lgG4, optionally an Fe region that has been modified to alter at least one of the effector functions, half-life, proteolysis or glycosylation, where optionally the Fe region contains one or more mutations that alter or abolish N- and / or 0-glycosylation. The invention further provides anti-MCT1 antibodies or antigen-binding fragments thereof or fusion polypeptides, chimeric antigen receptors (CARs), multispecific antigen-binding polypeptides, or multispecific or bispecific antibody polypeptides according to any of the foregoing, or a cell expressing any of the above, which binds to human MCT1 with an affinity (KD) of less than 100 nM, less than 50 nM, or less than 10 nM. The invention further provides anti-MCT1 antibodies or antigen-binding fragments thereof or fusion polypeptides, chimeric antigen receptors (CARs), multispecific antigen-binding polypeptides, or multispecific or bispecific antibody polypeptides according to any of the foregoing, or a cell expressing any of the above according to any of the above embodiments, which additionally has one or more of the following modifications: (i) is conjugated to a cytotoxic agent; (ii) is comprised of a bispecific antibody; (iii) is comprised of a multi-specific antigen-binding protein; (iv) is conjugated with a tag; and (v) is conjugated to another therapeutic agent, optionally an immunosuppressive agent or a chemotherapeutic agent. The invention further provides anti-MCT1 antibodies or antigen-binding fragments thereof or fusion polypeptides, chimeric antigen receptors (CARs), multispecific antigen-binding polypeptides, or multispecific or bispecific antibody polypeptides according to any of the foregoing, or a cell expressing any of the foregoing, wherein the label is a chemiluminescent label, a paramagnetic label, an MRI contrast agent, a fluorescent label, a bioluminescent label, or a radioactive label, or the cytotoxic agent is a moiety that inhibits DNA, RNA, or protein synthesis; a radionuclide; or a ribosomal inhibitory protein. The invention further provides anti-MCT1 antibodies or antigen-binding fragments thereof or fusion polypeptides, chimeric antigen receptors (CARs), multispecific antigen-binding polypeptides, or multispecific or bispecific antibody polypeptides according to any of the foregoing, or a cell expressing any of the foregoing according to any of the foregoing, which is suitable for treating a human subject having an autoimmune, inflammatory or allergic condition; metabolic disorder (eg, diabetes), polycystic kidney disease (ADPKD), cancer; transplant recipient or EIHI or any other condition in which decreased numbers and / or activity of effector T cells, for example, CD3+ T cells, CD4+ T cells, and / or CD8+ T cells, and / or increased activity and / or numbers of zncRan / nznz / q / Yi suppressor T cells or Tr1 is therapeutically desirable. The invention further provides anti-idiotypic antibodies or antigen-binding fragments thereof raised against an anti-MCT1 antibody or antigen-binding fragment thereof according to any of the foregoing, which optionally neutralizes one or more biological effects of the anti-MCT1 antibody. -MCT1 or antigen-binding fragment thereof to which it binds. The invention further provides anti-anti-idiotypic antibodies or antigen-binding fragments thereof raised against an anti-idiotypic antibody or antigen-binding fragment thereof in accordance with the above, optionally wherein the anti-anti-idiotypic antibody or antigen-binding fragment thereof neutralizes the anti-idiotypic antibody or antigen-binding fragment thereof to which it binds. The invention further provides methods of using the anti-idiotypic antibody described above to control in vivo levels of said anti-MCT1 antibody or antigen-binding fragment thereof in a subject or to neutralize the in vivo effects of said anti-MCT1 antibody. or antigen-binding fragment thereof in a subject. The invention further provides polynucleotides encoding anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide or anti-MCT1 antibody. MCT1 or antigen-binding fragment or anti-anti-MCT1 antibody or antigen-binding fragment according to any of the above, expression vectors containing the same host cells and comprising said polynucleotides or expression vectors optionally an immune cell human, for example, a T lymphocyte, B lymphocyte or an NK cell. The invention further provides pharmaceutical or diagnostic compositions comprising an effective amount of the anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or antibody polypeptide. multispecific or bispecific or anti-anti-MCT1 antibody or antigen-binding fragment or anti-MCT1 antibody or antigen-binding fragment according to any of the above or a cell expressing any of the above, for example, which are suitable for use in human or non-human treatment or prophylaxis. The invention further provides methods of producing an isolated anti-MCT1 antibody or antigen-binding fragment thereof comprising culturing a host cell as described above under conditions that allow expression of the antibody or antigen-binding fragment thereof; and recovering the antibody or antigen-binding fragment thereof from the culture medium or host cell. The invention further provides pharmaceutical compositions comprising a pharmaceutically effective amount of an isolated anti-MCT1 antibody or antigen-binding fragment thereof, anti-idiotypic antibody, fusion polypeptide, chimeric antigen receptor (CAR), antigen-binding polypeptide multispecific or multispecific or bispecific antibody polypeptide or a cell expressing any of the above, for example, those comprising a zncRan / nznz / q / Yi pharmaceutical diluent, carrier or excipient and optionally which may comprise another therapeutic agent, for example, a mitochondrial inhibitor and / or a biguanide and / or another monocarboxylate transporter (MCT inhibitor), for example an inhibitor of SLC16A1, SLC16A2, SLC16A3, SLC16A4, SLC16A5, SLC16A6, SLC16A7, SLC16A8, SLC16A9, SLC16A10, SLC16A11, SLC16A12 , SLC16A13 or SLC16A14 or inhibitor of MCT1, MCT2, MCT3, MCT4, MCT5, MCT6, MCT7, MCT8, MCT9 or MCT10 wherein said inhibitor can i Inhibit one or more of the above transporters and further said inhibitor optionally comprises a small molecule, RNAi, antibody, antibody fragment or a fusion protein or wherein said other active agent is selected from metformin, phenformin, alexidine, bisbiguanide, buformim, chlorhexidine, chlorproguanil, phenylbiguanide, polyaminopropyl biguanide, polyhexanide, moroxidine, glipizide, glyburide, repaglinide, saxagliptin, sitagliptin, pirvinium pamoate, proguanil, doxycycline, atovaquone, canagliflozin, glitazones (for example troglitazone, pioglitazone, rosiglitazone), tigeporcycline, thiazolides nitazoxanide), salicylanilides (eg, closantel, oxyclozanide, niclosamide), perhexiline, propronolol, fenofibrate, miconazole, nefazodone, pentamidine, hydrocortisone, metaiodobenzylguanidine, lonidamine, alpha-tocopheryl succinate (primary form of vitamin E), carbonic anhydrase, ME344 (MEI Pharma), HIF1a inhibitors (for example, chrysin, ketomin a, dimeth-bisphenol A, BAY84-2243), SR13800, dimethyloxaloylglycine (DMOG), carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP), carbonylcyanide m-chlorophenylhydrazone (CCCP), antimycin A, oligomycin, salinomycin, dinitrophenol, rotenone, phenformin, tyrphostin 9 , atpenine A5, berberine, azide, cyanide, nitrous oxide, arsenic trioxide, pyrvinium, canagliflozin, rosiglitazone, amobarbital, Honokol, arctigenin, caffeic acid phenyl ester, perphenazine, trifluoroperazine, methylglyoxal, and combinations comprising any of the above. The invention further provides methods of inhibiting the activity and / or number of effector T cells, eg, CD3+, CD4+ and / or CD8+ effector T cells in a subject in need thereof, comprising administering to the subject a therapeutically or prophylactically effective amount of an anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide, or multispecific or bispecific antibody polypeptide according to any of the above, or a cell expressing at least one of the foregoing or a pharmaceutical composition containing a therapeutically or prophylactically effective amount of any of the foregoing. The invention further provides methods of increasing the activity and / or number of effector T cells, eg, Tr1 or suppressor T cells, in a subject in need thereof, comprising administering to the subject a therapeutically or prophylactically effective amount of an anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide, or multispecific or bispecific antibody polypeptide according to any of the foregoing, or a cell expressing at least one of the above above or a pharmaceutical composition containing a therapeutically or prophylactically effective amount of any of the above. The invention further provides methods for inhibiting the activity and / or number of zncRan / nznz / q / Yi T lymphocytes, e.g., effector CD3+, CD4+ and / or CD8+ T cells and increasing the activity and / or number of lymphocytes. T suppressors or Tr1 in a subject in need thereof comprising administering to the subject a therapeutically or prophylactically effective amount of an anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), binding to the multispecific antigen or multispecific or bispecific antibody polypeptide according to any of the above or a cell expressing at least one of the above or a pharmaceutical composition containing a therapeutically or prophylactically effective amount of any of the above, for example, wherein the subject has an autoimmune, allergic, inflammatory condition, metabolic disorder, cancer, transplant recipient, cell therapy, EIHI condition, polycystic kidney disease (ADPKD) characterized by increased activity of effector T cells, eg, CD3+, CD4+, or CD8+ and / or decreased Tr1 or suppressor T cell activity and / or decreased the number of suppressor T lymphocytes or Tr1. The invention further provides methods of preventing or treating an autoimmune condition, allergic condition, inflammatory condition, metabolic disorder, cancer, transplant recipient, cell therapy recipient, EIHI condition, polycystic kidney disease (ADPKD), or symptoms associated with any such condition. comprising administering to a subject in need thereof a prophylactic or therapeutic effective amount of an anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or polypeptide of multispecific or bispecific antibody according to any of the foregoing or a cell expressing at least one of the foregoing or a pharmaceutical composition containing a therapeutically or prophylactically effective amount of any of the foregoing, for example, wherein the autoimmune condition, allergic condition, inflammatory condition, metabolic disorder, cancer, transplant recipient, cell therapy recipient, EIHI condition, polycystic kidney disease (ADPKD) characterized by increased activity of effector T cells, eg, CD3+, CD4+, or CD8+, and / or decreased suppressor T-cell or Tr1 activity and / or decreased number of suppressor T-cells or Tr1 or optionally wherein the metabolic disorder comprises Danon's disease, diabetes mellitus, Duarte galactosemia, MDP syndrome, metabolic myopathy, methylenetetrahydrofolate reductase deficiency , Winchester syndrome, salicylate sensitivity, X-linked hypophosphatemia, alcoholic ketoacidosis, allergic reaction to alcohol, alpha-aminoadipic and alpha-ketoadipic acidosis, high anion gap metabolic acidosis, gout, refeeding syndrome, exercise-associated hyponatremia, pancreatitis, pancreatitis and Metab-L or optionally wherein the condition is mediated at least in part by li Activated T lymphocytes or B lymphocytes and / or cells expressing MCT1. The invention further provides methods according to any of the foregoing, wherein administration of the antibody or antigen-binding fragment thereof or fusion protein has one or more of the following effects: (i) inhibits lactate transport in activated T cells or B cells; (ii) inhibits the transport of bromopyruvate toxin in activated T lymphocytes or B lymphocytes; zncRan / nznz / q / Yi (iii) inhibits the proliferation of CD3 / CD28 stimulated T cells; (iv) inhibits the proliferation of activated T lymphocytes; (v) inhibits the production and / or secretion of one or more inflammatory cytokines; (vi) does not inhibit the production and / or secretion of IL-2; (vii) increases urinary ketone production; (viii) increases survival time; (ix) decreases graft rejection; (x) increases the proportion or activity of regulatory T cells (Tregs); (x¡) the proportion of CD4+ T lymphocytes that are Tregs increases; (x11) decreases the proportion of lgG1+ B lymphocytes; (xiii) the proportion of germinal center B lymphocytes decreases; (xiv) does not inhibit lactate transport in human RBCs; (xv) decreases T-lymphocyte activation; and (xvi) decreases the activity of cytotoxic T lymphocytes. The invention further provides methods according to any of the foregoing, which are used to treat or prevent at least one of lupus, graft rejection, graft-versus-host disease (GVHD), type 1 or 2 diabetes, or obesity. The invention further provides methods according to any of the above, wherein the efficacy of treatment is monitored by measurement of urinary ketones, an increase in the number of TR1 lymphocytes, reduced or increased expression of a selected biomarker of an inflammatory cytokine , IFNy, GM-CSF, TNFa, IL-10, IL-6, IL-2, TIGIT, PD1, granzyme B, by a decrease in the number of effector T lymphocytes and / or hCD3+ cells, suppression of PMBC proliferation or a combination of any of the above. The invention further provides methods for evaluating the therapeutic efficacy of an anti-MCT1 antagonist antibody comprising detecting its effect in vitro or in vivo on any of the above: urinary ketones, the number of TR1 lymphocytes, the expression of a biomarker selected from an inflammatory cytokine, IFNy, GM-CSF, TNFa, IL-10, IL-6, IL-2, TIGIT, PD1, granzyme B, a decrease in the number of effector T lymphocytes and / or hCD3+ cells, suppression of proliferation from PMBC or a combination of any of the above. The invention further provides methods according to any of the foregoing, for treating or preventing a recurrence of cancer comprising administering to a subject in need thereof a therapeutically or prophylactically effective amount of an anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide according to any of the above or a cell expressing at least one of the above or a pharmaceutical composition containing a therapeutically or prophylactically effective amount of any of the foregoing, eg, wherein the tumor cells express MCT1 or the subject is a mammal or the subject is a mammal selected from human, non-human primates or rodents. zncRan / nznz / q / Yi The invention further provides methods of inhibiting or reducing the activity of activated T lymphocytes or B lymphocytes, comprising contacting said activated cells with an anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide or a cell expressing at least one of the foregoing according to any of the foregoing. The invention further provides methods according to any of the foregoing, wherein an anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody or a cell expressing at least one of the above according to any of the above is administered as monotherapy. The invention further provides methods according to any of the foregoing, wherein an anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody or a cell expressing at least one of the above in accordance with any of the above is administered in combination with a second therapeutic agent, for example, wherein the therapeutic agent is selected from an immunosuppressive drug, a chemotherapeutic agent , biguanide, for example, metformin or another antidiabetic agent, or an anti-inflammatory agent or said other therapeutic agent is a mitochondrial inhibitor and / or a biguanide or said other therapeutic agent is selected from metformin, phenformin, alexidine, bisbiguanide, buformim, chlorhexidine, chlorproguanil, phenylbiguanide, polyaminopropyl biguanide, polyhexanide, moroxidine, g lipidizide, glyburide, repaglinide, saxagliptin, sitagliptin, pirvinium pamoate, proguanil, doxycycline, atovaquone, canagliflozin, glitazones (for example troglitazone, pioglitazone, rosiglitazone), tigecycline, thiazolides (for example, nitazoxanide), salicylanilides (for example, closantel, oxyclozanide , niclosamide), perhexiline, propronolol, fenofibrate, miconazole, nefazodone, pentamidine, hydrocortisone, metaiodobenzylguanidine, lonidamine, alpha-tocopheryl succinate (primary form of vitamin E), carbonic anhydrase, ME344 (MEI Pharma), HIF1a inhibitors (for example, chrysin , ketomine, dimeth-bisphenol A, BAY84-2243), SR13800, dimethyloxaloylglycine (DMOG), carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP), carbonylcyanide m-chlorophenylhydrazone (CCCP), antimycin A, oligomycin, salinomycin, dinitrophenol, rotenone, phenformin, tyrphostin 9, Atpenine A5, Berberine, Azide, Cyanide, Nitrous Oxide, Arsenic Trioxide, Pyrvinium, Canagliflozin, Rosiglitazone, Amobarbital, Hono kol, arctigenin, caffeic acid phenyl ester, perphenazine, triflouroperazine, methylglyoxal, and combinations comprising any of the foregoing. The invention further provides methods according to any of the above, wherein the anti-MCT1 antibody, antigen-binding fragment thereof, fusion protein or pharmaceutical composition is administered enterally, parenterally or topically. The invention further provides methods for monitoring the efficacy of treatment with an antibody or antigen-binding fragment thereof or fusion protein that binds to MCT1 and reduces zncRan / nznz / q / Yi MCT1-mediated lactate transport comprising measuring the level of ketones in urine. The invention further provides methods for diagnosing a condition selected from an autoimmune, inflammatory, or allergic condition; a cancer; EIHI; polycystic kidney disease (ADPKD); diabetes or other metabolic disorder, and / or a condition associated with the upregulation of MCT1, wherein said method comprises: (i) isolating the cells responsible for mediating the condition; (ii) contacting said cells with an anti-MCT1 antibody or antigen binding fragment thereof or MCT1 binding fusion protein; and (iii) detecting the level of anti-MCT1 antibody or antigen-binding fragment or MCT1-binding fusion protein thereof bound to said cells. The invention further provides methods of treatment and detection as described above wherein the condition is autoimmune, inflammatory, transplantation, GVHD, metabolic (eg diabetes), EIHI disorder; polycystic kidney disease (ADPKD); or allergic condition, eg, where the condition is autoimmune, inflammatory, transplantation, GVHD, metabolic disorder (eg, diabetes), polycystic kidney disease (ADPKD), or allergic condition, and the cells are activated T cells or B cells or the condition is cancer and the cells are tumor cells or the condition is EIHI and the cells are beta cells. The invention further provides methods of treatment and detection as described above wherein the anti-MCT1 antibody or antigen-binding fragment thereof or MCT1-binding fusion protein comprises one or more of the following: (i) competes with an anti-MCT1 antibody selected from any of Ab1-Ab95 or another anti-MCT1 antibody comprising the same CDRs as any of the above anti-MCT1 antibodies; (ii) comprises the same CDRs as an anti-human MCT1 antibody selected from Ab1Ab95; (iii) comprises an affinity matured or humanized variant of a human anti-MCT1 antibody selected from Ab1-Ab95; (iv) competes with an antibody comprising a Vh domain that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity with the amino acid sequence of the Vh domain of MCT1 Ab1 (SEQ ID NO: 2) or with any Ab1-Ab59; and comprising a Vl domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% identity with the amino acid sequence of the Vl domain of MCT1 Ab1 (SEQ ID NO: 3) or with any of Ab2-Ab95; (v) comprises the heavy chain CDR sequences of MCT1 Ab1 (SEQ ID NOS: 4, 5, 6) and the CDR sequences of the light chain of MCT1 Ab1 (SEQ ID NOS: 7, 8, 9) or those of any of Ab2-Ab95; (vi) competes with an antibody that comprises or is itself composed of a Vh domain that zncRan / nznz / q / Yi has at least 80%, at least 85%, at least 90%, at least 95%, at least 98 %, at least 99%, or 100% identity with the amino acid sequence of the Vh domain of MCT1 Ab1 (SEQ ID NO: 2) or with any Ab2-Ab60; and comprises a Vl domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% identity with the amino acid sequence of the Vl domain of MCT1 Ab1 (SEQ ID NO: 3) or with any of Ab2-Ab60; (vii) competes with an antibody that comprises or is itself composed of a Vh domain that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity with the amino acid sequence of the Vh domain selected from those of SEQ ID NO: 2, 12, 14, 16, 19-32 or with any of Ab5-Ab60; and / or (viii) competes with an antibody that comprises or is itself composed of a Vique domain that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99 % or 100% identity with the amino acid sequence of the Vh domain selected from those of SEQ ID NO: 13, 15, 17 or 33-44 or with any of Ab5-Ab60; and / or (ix) comprises at least one peptide that comprises a sequence identical to SEQ ID NO: 6 or that comprises a sequence that differs from it by a maximum of 5, 4, 3, 2 or 1 residues, where said peptide is directly or indirectly linked to another polypeptide, for example, an antibody polypeptide or antibody domain, serum albumin, human or other primate serum albumin, adnectin, an affibody, a DARPin, an anticalin, glycol (PEG), monomethoxy PEG (mPEG), an XTEN molecule, an rPEG molecule or fragment, or a variant of any of the foregoing. Methods of the invention for detecting the expression of MCT1, optionally functional MCT1, by a cell comprising determining whether any of the anti-MCT1 antibodies according to any of the above embodiments bind to MCT1 expressed by said cell, for example, where the cell is human or non-human, for example, where the cell is obtained from a patient who has or is suspected of comprising an autoimmune, allergic, inflammatory condition, metabolic disorder, cancer, transplant recipient, recipient treatment, EIHI condition, polycystic kidney disease (ADPKD) or where the detection method is used to diagnose or monitor a disease or disease prognosis using a cellular sample obtained from a patient who has or is suspected of having comprising autoimmune, allergic, inflammatory condition, metabolic disorder, cancer, transplant recipient, cell therapy recipient, afe ction EIHI, polycystic kidney disease (ADPKD) characterized by cells comprising aberrant (increased) MCT1 expression or activity. In some embodiments, the antibody or antigen-binding fragment thereof is selected from the group consisting of: a monoclonal antibody; a monospecific antibody; a polyspecific antibody; a humanized antibody; a tetrameric antibody; a tetravalent antibody; a multispecific antibody; a single chain antibody; an antibody specific for zncRan / nznz / q / Yi domain; a single domain antibody; a domain deleted antibody; an scFc fusion protein; a chimeric antibody; a synthetic antibody; a recombinant antibody; a hybrid antibody; a mutated antibody; CDR-grafted antibodies; an antibody fragment; a Fab; an F(ab')2; a Fab' fragment; an Fv fragment; a single chain Fv fragment (scFv); an Fd fragment; a dAb fragment; multiple specific antibodies, diabodies; ByTEs, bivalent antibodies, a nanobody; a bivalent nanobody; a shark variable IgNAR domain; a VHH antibody; a camelid antibody; and a minibody. In some embodiments, the antibody or antigen-binding fragment thereof is a human, humanized, or chimeric antibody or antigen-binding fragment thereof. In some embodiments, the antibody or antigen-binding fragment thereof is an anti-MCT1 antibody that competes with or binds to this or the overlapping epitope of any of the antibodies identified herein as Ab1-Ab95, wherein said antibody or antigen-binding fragment optionally antagonizes one or more MCT1-associated functions, eg, inhibits MCT1-mediated lactate transport. In some embodiments, the antibody or antigen-binding fragment thereof is an anti-MCT1 antibody comprising at least 1, 2, 3, 4, 5, or all 6 CDRs as any of the anti-MCT1 antibodies identified. as Ab1-Ab95 herein, wherein said antibody or antigen-binding fragment optionally antagonizes one or more MCT1-associated functions, eg, inhibits MCT1-mediated lactate transport. In some embodiments, the antibody or antigen-binding fragment thereof is an anti-MCT1 antibody or antigen-binding fragment comprising a humanized, chimeric, scFv, or affinity matured derivative of any of the anti-MCT1 antibodies that are identified as Ab1-Ab95 herein, wherein said antibody or antigen-binding fragment optionally antagonizes one or more MCT1-associated functions, eg, inhibits MCT1-mediated lactate transport. In some embodiments, the antibody or antigen-binding fragment thereof is a fusion polypeptide or multispecific polypeptide comprising at least one anti-MCT1 antigen-binding domain comprising the same CDRs or heavy and / or light variable regions. that any of the anti-MCT1 antibodies identified as Ab1-Ab95 herein, wherein said fusion polypeptide or multispecific polypeptide optionally antagonizes one or more MCT1-associated functions, eg, inhibits MCT1-mediated lactate transport. In some embodiments, the anti-MCT1 antibody or antigen-binding fragment will comprise a heavy chain CDR3 sequence comprising 19, 20, 21, 22, 23, or 24 amino acid residues. In some embodiments, the heavy chain CDR3 sequence comprises 21, 22, or 23 amino acid residues. In some embodiments, the heavy chain CDR3 sequence is identical to or differs from SEQ ID NO: 6 by at most 5, 4, 3, 2, or 1 residues. In some embodiments, such substitutions, if present, comprise conservative amino acid substitutions or comprise prevailing substituent amino acids at the same zncRan / nznz / q / Yi position on the CDR3 heavy chain of human or rodent antibodies. In some embodiments, the antibody or antigen-binding fragment thereof competes for binding to MCT1 with a reference antibody, wherein the reference antibody comprises: Yo. the MCT1 Ab1 heavy chain CDR sequences (SEQ ID NOS: 4, 5, 6) and the MCT1 Ab1 light chain CDR sequences (SEQ ID NOS: 7, 8, 9); I heard. a Vh domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity to the amino acid sequence of the MCT1 Vh domain Ab1(SEQ ID NO: 2); and comprising a Vl domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% identity with the amino acid sequence of the Vl domain from MCT1 Ab1 (SEQ ID NO: 3). In some embodiments, the antibody or antigen-binding fragment thereof comprises the MCT1 Ab1 heavy chain CDR sequences (SEQ ID NOS: 4, 5, 6) and the MCT1 Ab1 light chain CDR sequences ( SEQ ID NOS: 7, 8, 9) In some embodiments, the antibody or antigen-binding fragment thereof comprises a Vh domain that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99 %, or 100% identity to the amino acid sequence of the Vh domain of MCT1 Ab1 (SEQ ID NO: 2); and comprises a Vl domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% identity with the amino acid sequence of the Vl domain of MCT1 Ab1 (SEQ ID NO: 3). In some embodiments, the antibody or antigen-binding fragment thereof comprises a Vh domain comprising the same CDRs comprised in the Vh domain of any of the anti-MCT1 antibodies identified herein as Ab1-Ab95 and / or comprises a Vl domain comprising the same CDRs as the Vh domain of any of the anti-MCT1 antibodies identified herein as Ab1-Ab83. In some embodiments, the antibody or antigen-binding fragment thereof comprises a Vh domain that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99 % or 100% identity to the amino acid sequence of the Vh domain of any of the anti-MCT1 antibodies identified herein as Ab1-Ab95 and / or comprises a Vl domain having at least 80%, at least 85%, at at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity to the amino acid sequence of the Vh domain of any of the anti-MCT1 antibodies identified herein as Ab1-Ab83. In some embodiments, the anti-MCT1 antibody or antigen-binding fragment will bind to one or more of the following residues of the epitope bound by anti-MCT1 antibodies according to the invention, i.e. any of Ab1-Ab95 , optionally wherein the residues constituting the epitopes are identified by alanine scanning. In some embodiments, the CDRs of the anti-MCT1 antibody or the zncRan / nznz / q / Yi antigen-binding fragment thereof will have a three-dimensional structure similar to that of MCT1 Ab1, as indicated by the positions of the alpha carbons in the corresponding CDRs that differ by a root mean square deviation (RMSD) of less than 2.0 Á, less than 1.0 Á, or less than 0.5 Á, as determined through structural alignment as shown in Figure Figure 21. The invention further provides an isolated anti-MCT1 antibody or an antigen-binding fragment thereof comprising a heavy chain polypeptide or variable heavy chain polypeptide having an amino acid sequence selected from SEQ ID NO: 2, 12, 14, 16, 1932, 45, 47, 49, 51,53, 55, 57, 59, 61,63, 65, 67, 69, 71, 73, 75, 77, 79, 81,83, 85, 87, 89, 91,93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153 and 155, and a variable light chain polypeptide or light chain polypeptide having an amino acid sequence selected from SEQ ID NO: 3, 13, 15, 17, 3344, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, 150, 152, 144, 146, 148, 150, 152, 154 and 156. The invention specifically provides an isolated anti-MCT1 antibody or an antigen-binding fragment thereof comprising a variable heavy chain polypeptide and a variable light chain polypeptide having an amino acid sequence selected respectively from the following: SEQ ID NO: 2 and 3; SEQ ID NO: 12 and 13; SEQ ID NO: 14 and 15; SEQ ID NO: 16 and 17; SEQ ID NO: 45 and 46; SEQ ID NO: 47 and 48; SEQ ID NO: 49 and 50; SEQ ID NO: 51 and 52; SEQ ID NO: 53 and 54; SEQ ID NO: 55 and 56; SEQ ID NO: 57 and 58; SEQ ID NO: 59 and 60; SEQ ID NO: 61 and 62; SEQ ID NO: 63 and 64; SEQ ID NO: 65 and 66; SEQ ID NO: 67 and 68; SEQ ID NO: 69 and 70; SEQ ID NO: 71 and 72; SEQ ID NO: 73 and 74; SEQ ID NO: 75 and 76; SEQ ID NO: 77 and 78; SEQ ID NO: 79 and 80; SEQ ID NO: 81 and 82; SEQ ID NO: 83 and 84; SEQ ID NO: 85 and 86; SEQ ID NO: 87 and 88; SEQ ID NO: 89 and 90; SEQ ID NO: 91 and 92; SEQ ID NO: 93 and 94; SEQ ID NO: 95 and 96; SEQ ID NO: 97 and 98; SEQ ID NO: 99 and 100; SEQ ID NO: 101 and 102; SEQ ID NO: 103 and 104; SEQ ID NO: 105 and 106; SEQ ID NO: 107 and 108; SEQ ID NO: 109 and 110; SEQ ID NO: 111 and 112; SEQ ID NO: 113 and 114; SEQ ID NO: 115 and 116; SEQ ID NO: 117 and 118; SEQ ID NO: 119 and 120; SEQ ID NO: 121 and 122; SEQ ID NO: 123 and 124; SEQ ID NO: 125 and 126; SEQ ID NO: 127 and 128; SEQ ID NO: 129 and 130; SEQ ID NO: 131 and 132; SEQ ID NO: 133 and 134; SEQ ID NO: 135 and 136; SEQ ID NO: 137 and 138; SEQ ID NO: 139 and 140; SEQ ID NO: 141 and 142; SEQ ID NO: 143 and 144; SEQ ID NO: 145 and 146; SEQ ID NO: 147 and 148; SEQ ID NO: 149 and 150; SEQ ID NO: 151 and 152; SEQ ID NO: 153 and 154 and SEQ ID NO: 155 and 156. The invention further provides an isolated antibody or antigen-binding fragment thereof comprising a Vh domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99 %, or 100% identity to the amino acid sequence of the Vh domain of MCT1 Ab1 (SEQ ID NO: 2); and comprising a Vl domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% identity with the amino acid sequence of the Vl domain of MCT1 Ab1 (SEQ ID NO: 3). The invention also provides a fusion protein comprising at least one zncRan / nznz / q / Yi peptide comprising a sequence identical to SEQ ID NO: 6 or comprising a sequence that differs from it by at most 5, 4 , 3, 2 or 1 residues, wherein said peptide is directly or indirectly linked to another polypeptide, for example, an antibody polypeptide or antibody domain, serum albumin, human or other primate serum albumin, adnectin, an affibody, a DARPin, an anticalin, glycol (PEG), monomethoxy PEG (mPEG), an XTEN molecule, an rPEG molecule or fragment, or a variant of any of the foregoing. In some embodiments, the antibody polypeptide or domain comprises a Fe polypeptide or fragment thereof, for example, a human IgG1, IgG2, IgG3 or IgG4 Fe region or fragment thereof. In some embodiments, such substitutions, if present, comprise conservative amino acid substitutions or comprise prevailing substituent amino acids at the same position in the CDR3 heavy chain of human or rodent antibodies. In some embodiments, the antibody or antigen-binding fragment thereof or fusion protein has one or more of the following properties when binding to MCT1 on the surface of an activated T cell or B cell: Yo. inhibits lactate transport; ii. inhibits bromopyruvate transport; iii. inhibits the transport of one or more monocarboxylates, pyruvate, branched-chain oxoacids derived from leucine, valine, and isoleucine, ketone bodies, acetoacetate, beta-hydroxybutyrate, acetate, lactic acid, cellular nutrients, metabolites, ions, hormones, lipids, and ketones ; iv. inhibits the proliferation of CD3 / CD28 stimulated T lymphocytes; v. inhibits the proliferation of activated T lymphocytes or B lymphocytes; saw. inhibits the production of one or more inflammatory cytokines; vile. increases the proportion or activity of regulatory T cells (Tregs); and vili. inhibits allogeneic activation in a mixed lymphocyte reaction. In some embodiments, the antibody or antigen-binding fragment thereof or fusion protein inhibits the production of one or more inflammatory cytokines upon binding to MCT1. In some embodiments, at least one of the one or more cytokines, eg, inflammatory cytokines where such cytokines can include any of the following: FGF2, FLT-3L, Fractalkine, G-CSF, GM-CSF, GRO, IFNa2, IFNy, IL-3, IL-5, IL-9, IL-10, IL-12p40, IL-12p70, IL-13, IL17a, IP-10, MCP-1, MDC, MIP-1a, MIP- 1b, SCD40L, TNFa and TNFp. In some embodiments, at least one of the one or more inflammatory cytokines is selected from IFNγ, GM-CSF, TNFα, IL-10, and IL-6. In some embodiments, the antibody or antigen-binding fragment thereof or fusion protein inhibits MCT1-mediated lactate transport in activated T cells with a Kd of less than 100 nM, less than 50 nM, or less than 10 nM. , as measured by a FLIPR lactate assay. In some embodiments, the antibody or antigen-binding fragment thereof or fusion protein does not: zncRan / nznz / q / Yi Yo. binds to MCT2, MCT3, MCT4, and / or CD147 as measured by flow cytometry; ii. inhibits the transport of MCT2, MCT3 and / or MCT4; iii. inhibits the production of IL-2; iv. inhibits lactate transport in monocytes; v. inhibits the proliferation of naïve, resting and / or regulatory T lymphocytes; saw. inhibits lactate transport in RBCs; vile. alters the expression of one or more T cell activation markers, optionally selected from CD25, CD54, CD69, CD95, CD98, CD147, CD154, CD278, CD279, and HLA-DR / DP / DQ. In some embodiments, the antibody or antigen-binding fragment thereof or fusion protein comprises an Fc region of human IgG1, IgG2, IgG3, or IgG4. In some embodiments, the antibody or antigen-binding fragment thereof or fusion protein comprises an Fe region that has been modified to alter at least one of effector functions, half-life, proteolysis, or glycosylation, where optionally the Fe region contains one or more mutations that alter or eliminate N- and / or O-glycosylation. In some embodiments, the antibody or antigen-binding fragment thereof or fusion protein binds to MCT1 with an affinity (Kd) of less than 100 nM, less than 50 nM, or less than 10 nM. In some embodiments, the antibody or antigen-binding fragment thereof or fusion protein additionally has one or more of the following modifications: Yo. is conjugated with a cytotoxic agent; Yo. is comprised of a bispecific antibody; iii. is comprised of a multispecific antigen-binding protein; iv. is conjugated with a label; and v. it is conjugated to another therapeutic agent, optionally an immunosuppressive agent or a chemotherapeutic agent. In some embodiments, the tag is a chemiluminescent tag, a paramagnetic tag, an MRI contrast agent, a fluorescent tag, a bioluminescent tag, or a radioactive tag. In some embodiments, the cytotoxic agent is a moiety that inhibits DNA, RNA, or protein synthesis; a radionuclide; or a ribosomal inhibitory protein. In some embodiments, the antibody or antigen-binding fragment thereof or fusion protein is suitable for treating a human subject having an autoimmune, inflammatory, or allergic condition; cancer; or EIHI. The invention also provides an anti-idiotypic antibody or antigen-binding fragment thereof raised against an anti-MCT1 antibody or antigen-binding fragment thereof according to any of the above embodiments, which optionally neutralizes one or plus biologic effects of anti-MCT1 antibody or antigen-binding fragment thereof to which zncRan / nznz / q / Yi binds. The invention further provides an anti-anti-idiotypic antibody or antigen-binding fragment thereof raised against the anti-idiotypic antibody or antigen-binding fragment thereof, optionally wherein the anti-anti-idiotypic antibody or antigen-binding fragment thereof antigen thereof neutralizes the anti-idiotypic antibody or antigen-binding fragment thereof to which it binds. Furthermore, in some embodiments, the invention relates to a method of using the anti-idiotypic antibody to control in vivo levels of said anti-MCT1 antibody or antigen-binding fragment thereof in a subject or to neutralize the effects of said anti-MCT1 antibody or antigen-binding fragment thereof. in vivo of said anti-MCT1 antibody or antigen-binding fragment thereof in a subject. The invention also provides an isolated polynucleotide encoding the anti-MCT1 antibody or antigen-binding fragment thereof or fusion protein according to any of the above embodiments. Additionally provided are expression vectors comprising such polynucleotides. The invention also provides a host cell comprising the expression vector. The invention further relates to a method of producing an isolated anti-MCT1 antibody or antigen-binding fragment thereof comprising culturing the host cell under conditions that allow expression of the antibody or antigen-binding fragment thereof; and recovering the antibody or antigen-binding fragment thereof from the culture medium or host cell. The invention further provides a pharmaceutical composition comprising a pharmaceutically effective amount of an isolated anti-MCT1 antibody or an antigen-binding fragment thereof or fusion protein or an isolated cell that is expressed according to any of the above embodiments. which may further comprise a pharmaceutical diluent, carrier or excipient. Also provided herein is a method of treating or preventing an autoimmune, allergic, or inflammatory condition comprising administering to a subject in need thereof a therapeutically or prophylactically effective amount of an anti-MCT1 antibody, or antigen-binding fragment thereof. , or fusion protein according to any of the above embodiments or a pharmaceutical composition as described above. In some embodiments, the condition is mediated, at least in part, by activated T cells or B cells. In some embodiments, administration of the anti-MCT1 antibody or antigen-binding fragment thereof or fusion protein has one or more of the following effects: Yo. inhibits lactate transport in activated T-lymphocytes or B-lymphocytes; Yo. inhibits bromopyruvate toxin transport in activated T-lymphocytes or B-lymphocytes; iii. inhibits the proliferation of CD3 / CD28 stimulated T lymphocytes; iv. inhibits the proliferation of activated T lymphocytes; v. inhibits the production and / or secretion of one or more inflammatory cytokines; saw. does not inhibit the production and / or secretion of IL-2; vii. increases the production of ketones in urine; viii. increases survival time; ix. decreases graft rejection; zncRan / nznz / q / Yi x. increases the proportion or activity of regulatory T cells (Tregs); xi. the proportion of CD4+ T cells that are Tregs increases; xii. the proportion of IgG1+ B lymphocytes decreases; xiii. decreases the proportion of B lymphocytes from the germinal center; xiv. does not inhibit lactate transport in human RBCs; xv. decreases the activation of T lymphocytes; and xvi. decreases the activity of cytotoxic T lymphocytes. In some embodiments, the method is used to treat or prevent lupus. In some embodiments, the method is used to treat or prevent graft rejection. In some embodiments, the method is used to treat or prevent graft-versus-host-disease (GVHD). In some embodiments, the method is used to treat or prevent diabetes. In some embodiments, the method is used to treat or prevent obesity. In some embodiments, the efficacy of the treatment is monitored by measurement of urine ketones. The invention further provides a method of treating or preventing a recurrence of cancer comprising administering to a subject in need thereof a therapeutically or prophylactically effective amount of an anti-MCT1 antibody, or antigen-binding fragment thereof, or fusion protein. according to any one of the above embodiments or a pharmaceutical composition according to the above embodiments. In some embodiments, the tumor cells express MCT1. In some embodiments, the subject is a mammal. In some embodiments, the mammal is a human. In some embodiments, the mammal is a non-human primate. In some embodiments, the mammal is a rodent. The invention also provides a method for inhibiting or reducing the activity of activated T-lymphocytes or B-lymphocytes, comprising contacting said activated cells with an anti-MCT1 antibody, or antigen-binding fragment thereof, or fusion protein according to any of the above embodiments. In some embodiments, the anti-MCT1 antibody or antigen-binding fragment thereof or fusion protein is administered as a monotherapy. In some embodiments, the anti-MCT1 antibody or antigen-binding fragment thereof or fusion protein is administered in combination with a second therapeutic agent. In some embodiments, the therapeutic agent is selected from an immunosuppressive drug or a chemotherapeutic agent. In some embodiments, the anti-MCT1 antibody, MCT1 antigen-binding fragment, fusion protein, pharmaceutical composition is administered enterally, parenterally, or topically. The invention further provides a method for monitoring the efficacy of treatment with an antibody or antigen-binding fragment thereof or fusion protein that binds to MCT1 and zncRan / nznz / q / Yi reduces MCT1-mediated lactate transport comprising measure the level of ketones in urine. In another aspect, the invention provides a method for diagnosing a condition selected from an autoimmune, inflammatory, or allergic condition; a cancer; EIHI; and a condition associated with the upregulation of MCT1, said method comprises: Yo. isolating the cells responsible for mediating the condition; Yo. contacting said cells with an anti-MCT1 antibody or antigen binding fragment thereof or MCT1 binding fusion protein; and iii. detecting the level of anti-MCT1 antibody or antigen-binding fragment or MCT1-binding fusion protein thereof bound to said cells. In some embodiments, the condition is an autoimmune, inflammatory, or allergic condition, and the cells are activated T cells or B cells. In some embodiments, the condition is cancer and the cells are tumor cells. In some embodiments, the condition is EIHI, and the cells are beta cells. In some embodiments, the anti-MCT1 antibody or its antigen-binding fragment or MCT1-binding fusion protein: Yo. competes with an antibody comprising the MCT1 Ab1 heavy chain CDR sequences (SEQ ID NOS: 4, 5, 6) and the MCT1 Ab1 light chain CDR sequences (SEQ ID NOS: 7, 8, 9) or an anti-MCT1 antibody selected from any of Ab1-Ab95; Yo. competes with an antibody comprising a Vh domain that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity to the sequence of amino acids from the Vh domain of MCT1 Ab1 (SEQ ID NO: 2) or to any Vnde domain of Ab1-Ab95; and further comprising a Vl domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity with the amino acid sequence of the domain. Vl of MCT1 Ab1 (SEQ ID NO: 3) or to any Vnde domain of Ab1-Ab95; iii. comprises the heavy chain CDR sequences of MCT1 Ab1 (SEQ ID NOS: 4, 5, 6) and the MCT1 Ab1 light chain CDR sequences (SEQ ID NOS: 7, 8, 9); iv. comprises a Vh domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity with the amino acid sequence of the Vh domain of MCT1 Ab1 (SEQ ID NO: 2); and comprises a Vl domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% identity with the amino acid sequence of the Vl domain of MCT1 Ab1 (SEQ ID NO: 3); either v. comprises at least one peptide that comprises a sequence identical to SEQ ID NO: 6 or that comprises a sequence that differs from it by, at most, 5, 4, 3, 2 or 1 residues, wherein said peptide is linked directly or indirectly to another polypeptide, for example, an antibody polypeptide or antibody domain, serum albumin, zncRan / nznz / q / Yi human or other primate serum albumin, adnectin, an affibody, a DARPin, an anticalin, glycol (PEG) , monomethoxy PEG (mPEG), an XTEN molecule, an rPEG molecule or fragment, or variant of any of the foregoing. DETAILED DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS Figure 1 illustrates that the metabolic states of leukocytes are associated with different immunological properties (REF. 33). Resting, memory, and Treg cells are dependent on oxidative phosphorylation (Oxphos) (left), while effector T cell proliferation and effector function are highly dependent on glycolysis after antigen activation (right). Figure 2 shows that CD3 / CD28 activation induces increased MCT1 and MCT4 expression and that ICso values ​​for AZ3965 inhibition of proliferation do not change in the presence of high (Donor 1) or low (Donor 1) expression levels of MCT4. Donor 2) (S = stimulated for 3 days; NS = not stimulated; BSG = Basigin / CD147). From left to right for Donor 1, bars correspond to unstimulated expression of MCT2, MCT4, and BSG, followed by stimulated expression of MCT1, MCT2, MCT4, and BSG. Note: Donor 1 did not have MCT1 expression in unstimulated cells. From left to right for Donor 2, bars correspond to unstimulated expression of MCT1, MCT2, MCT4, and BSG, followed by stimulated expression of MCT1, MCT2, MCT4, and BSG. Figure 3 contains the results of a lactate FLIPR assay with AZ3965. AZ3965 inhibits lactate transport in human CD4+ T cells (CD4), CD8+ T cells (CD8), B-cell lymphoma cells (Daudi), and peripheral blood mononuclear cells (PBMC), but not monocytes (Mono). From top to bottom at 100 nM AZ3965, the curves correspond to Daudi, CD4, CD8, PBMC, and Mono. Figure 4 contains the results of a human T cell proliferation assay with a small molecule MCT1 inhibitor. Inhibition of MCT1 leads to inhibition of T lymphocyte proliferation with an ICso of 0.54 nM. Figure 5 contains the results of a human mixed lymphocyte reaction (MLR) assay with a small molecule MCT1 inhibitor. T cell proliferation in this MLR assay was inhibited with an ICso of 1.34 nM. Figure 6 shows the inhibition of T cell cytokine secretion in vitro after administration of AZ3965. T cells were activated with CD3 / CD28 for 5 days prior to drug administration. The red areas of the figure (upper expression) have been outlined in a black dotted line. All other areas are blue (bottom expression). The intensity of the shading also indicates expression. AZ3965 inhibits the secretion of IFNγ, GM-CSF, TNFα, IL-10, and IL-6, but not IL-2. Figures 7A-J show the expression of various T cell surface markers on activated T cells after 4 days of treatment with 100 nM zncRan / nznz / q / Yi small molecule MCT1 inhibitor or no treatment, compared to an unstained control. In each panel, the control that does not stain for antibody is the leftmost peak. In each panel, there is no significant difference in staining between the treated and untreated conditions. The untreated condition is the slightly higher curve for all panels except Figure 7H, where the treated condition curve is slightly higher. Results shown herein are for the following cell surface producers: CD25 (Figure 7A); CD54 (Figure 7B); CD69 (Figure 7C); CD95 (Figure 7D); CD98 (Figure 7E); CD147 (Figure 7F); CD154 (Figure 7G); CD278 (Figure 7H); CD279 (Figure 7I); and HLA-DR, DP, DQ (Figure 7J). Figure 8 shows the results of a xeno-GVHD assay with AZ3965. AZ3965 blocks GVHD morbidity until drug withdrawal and outperforms a JAK inhibitor. Figure 9 shows a dose-dependent increase in the frequency of tissue Tregs for the xeno-GVHD experiment (Figure 8) during the AZ3965 dose period. Figure 10 shows the effects of a small molecule inhibitor of MCT1 on graft rejection. Both visually and in a graft analysis on day 10, compound administration 25 mg / kg 2x / day reduced graft rejection. Figures 11A-B show that administration of AZ3965 reduces the proportions of lgG1 B cells and germinal center B cells in mice challenged with sheep RBCs. Figure 11A shows a decrease in IgG1 B cells with the administration of 2.5 mpk AZ3965 and Figure 11B shows a decrease in germinal center B cells with the same dose. Figures 12A-D show the cross-reactivity of MCT1 Ab1 as assessed by flow cytometric measurements of MCT1 binding on the surface of PBMCs from different species. Figure 12A shows that MCT1 Ab1 binds to MCT1 on the surface of human PBMCs, and that it binds to a greater extent to stimulated cells. Figure 12B shows that MCT1 Ab1 binds to Macaca fascicularis MCT1. Figure 12C shows that MCT1 Ab1 binds to rabbit MCT1. Figure 12D shows that MCT1 Ab1 does not bind to rat MCT1. Figures 13A-B show that MCT1 Ab1 binds to activated T cells. MCT1 Ab1 does not stain naïve cells (Figure 13A), but stains the surface of activated CD3 / CD28 cells on day 3 (Figure 13B). The only staining in Figure 13A corresponds to the core staining, confirming the presence of the naïve T cells. Figure 14 shows that MCT1 Ab1 inhibits lactate transport by MCT1 in activated T cells in vitro. Rat Ig control and buffer control curves show no change compared to control, whereas MCT1 Ab1 resulted in decreased lactate transport compared to control with a Kd of 7.6 nM (lower curve in the control). right side). Figure 15 shows that MCT1 Ab1 inhibits bromopyruvate toxin transport as measured by MCT 1 Ab1 protection from cell death using ATPIite (Kd = 1.2 nM). Figure 16 contains the results of a T cell proliferation assay, where MCT 1 Ab1 inhibited T cell proliferation with an ECso of 1.3 nM. Figure 17 shows that MCT1 Ab1 inhibited allogeneic activation in a dose dependent zncAan / nznz / q / Yi manner in a human mixed lymphocyte reaction. Figures 18A-B show the expression of MCT1 on the surface of RBCs from five different species. In Figure 18A, MCT1 Ab1 staining of purified Macaca fascicularis RBCs (right) shows MCT1 expression in the plasma membrane, in contrast to purified human RBCs (20 donors, left) lacking expression. In the left panel, the secondary Ab only condition, the control condition, and the MCT1 Ab1 stained condition show no MCT1 staining. In Figure 18B, the staining shows MCT1 expression on the surface of rabbit RBCs (left), but none on the surface of rat (middle) or beagle (right) RBCs. Figure 19 shows that human RBCs do not require MCT1 for lactate transport. Neither MCT1 Ab1 nor AZ3965 inhibition of MCT1 blocked lactate transport in human RBCs purified by FLIPR-based transport assays (REF. 1, 2). None = no inhibitor. Figure 20 contains the results of flow cytometric analysis of lupus B lymphocytes. Example MCT1 staining of B cell populations from one healthy patient and two lupus patients indicates a significant increase in MCT1 staining for lupus patients. Figure 21 contains a graphical representation of the crystal structure of the MCT1 Ab1 Fab, deposited with this application as 43260_4200-MCT1_Ab1 .pdb. In the image, the Vh CDR3 can be seen to extend beyond the antigen-binding portion of the surface. Figure 22 schematically shows that while MCT1 is involved in several functions, there are redundant pathways that prevent toxicity outside the lymphatic system, but that MCT1 has a single transporter pathway in the lymphoid system (eg, B, T cells). Figure 23 shows that Macaca fascicularis red blood cells (RBC) express high levels of MCT1. Figure 24 contains experiments indicating that Macaca fascicularis tolerate repeated administration of an anti-MCT1 (Ab1) antibody at 50mpk. Figure 25 contains PK data observed in Macaca fascicularis suggesting that there is good binding of the administered anti-MCT1 antibody (Ab1) and the results further indicate that at Ab1 dose rates > 5mpk that the RBC sink is saturated. Figure 26 contains experiments evaluating target tissues (muscle, testis and eye) in a tamoxifen-inducible MCT1 knockout mouse. Figure 27 shows that MCT1 knockout mice animals had smaller testes and a microscopic finding indicating some sperm degeneration. Figure 28 shows that the MCT1 KO phenotype confers robust tamoxifen-inducible inhibition of MCT1 expression in several target tissues that were tested, i.e., thymus, spleen, lymph nodes, testes, and retina, relative to expression of a housekeeping control gene (HPRT). Figure 29 shows phenotypic changes in the testes observed in knockout mice. As shown, spermatid degeneration was observed in the testis of all zncAan / nznz / q / Yi mice. Inactivated MCT1 (lack of late-stage spermatids and spermatocytes, decreased tubular cellularity, vacuolation, and cell debris). Figure 30 further compares the histology of the testes in WT and MCT1 KO mice and shows increased spermatid degeneration in knockout mice relative to wild type. Figure 31 summarizes binding and functional results comparing different commercially available anti-MCT1 antibodies. The Figure contains MFI (TOP, flow cytometry, live cell cell fixation) and bromopyruvate functional assay results (Bottom, RLU) using all anti-MCT1 antibodies (Mabs and polyclonals) sold by Abcam. (Catalog numbers are listed in the figure.) Figure 32 contains results of experiments that detected the antagonistic activity of different anti-MCT1 antibodies described herein, ie, INX420, INX444, INX356, INX352, and INX453 based on their relative ability to block MCT1 transporter activity in a bromopyruvate assay. Figure 33 contains an alignment of the variable heavy regions of different anti-MCT1 antibodies described herein, ie, INX420, INX444, INX356, INX352 and INX453. Figure 34 contains an alignment of the variable light regions of different anti-MCT1 antibodies described herein, ie, INX420, INX444, INX356, INX352 and INX453. Figures 35A and B respectively show the binding of anti-MCT1 disclosed herein to 293 MCT1+ cells and their relative functionality in bromopyruvate toxin transport assays. Figures 36A-D contain experimental data comparing two anti-MCT1 antibodies disclosed herein, ie, INX310 and INX420 with respect to their relative abilities to inhibit CD4+ and CD8+ T cell proliferation. Figures 37A-D contain experimental data showing that an anti-MCT1 antibody described herein, ie, INX420, increases the frequency of PD1+TIGIT+ cells in vitro compared to a small molecule MCT1 inhibitor compound. Figures 38A-B contain experimental data showing that PD1+TIGIT+Tr1 cells suppress PMBC proliferation. Figure 39 contains experimental data showing that blocking IL-10 signaling with an IL-10 antagonist (anti-IL-10RB) does not affect the suppression of PMBC proliferation by an anti-MCT1 antibody disclosed herein, i.e. INX420. Figure 40 contains experimental data showing treatment of xenoGvHD animals with anti-MCT1 antibodies described herein, ie, INX420 and INX310, resulted in significant decreases in the number of CD3+, CD4+, and CD8+ effector T cells and increases in Tr1 lymphocytes compared to xeno-GvHD animals treated with a control antibody. Figures 41A-C contain experimental data showing treatment of xeno-GvHD animals with anti-MCT1 antibodies described herein, ie, INX420, INX413 and INX310, zncAan / nznz / q / Yi resulted in significant decreases in the number of CD3+, CD4+ and CD8+ effector T cells compared to xeno-GvHD animals treated with a control antibody. Figure 42 contains results of experiments showing that administration of anti-MCT1 antibodies, i.e., INX420 and INX310, in the xeno-GvHD animal model resulted in increased survival, long-term protection, and tolerance induction compared to animals treated with control antibody. Figure 43 contains biomarker expression data showing that TIGIT and PD1 are expressed by a substantial amount (75%) of human T cells in the xeno-GvHD animal model and comprise putative Tr1 cell biomarkers. Figure 44 contains biomarker expression data showing that TIGIT and PD1 comprise putative Tr1 cell biomarkers and that putative Tr1 cells expressing these markers suppress effector T cell proliferation. Figure 45 contains biomarker expression data showing that Tr1 lymphocytes express high levels of Granzyme B and do not express FOXP3 or Blimpl. Figures 46A-C contain experimental results showing that NSG mice treated with an anti-MCT1 antibody (INX420) comprise reduced numbers of hCD3+ effector T cells compared to control antibody-treated animals. Figures 47A-B contain experimental results showing that Tr1 cells suppress the proliferation of hCD3+ effector T cells and PMBC after CD23 / CD28 stimulation. Figure 48 schematically depicts the kinetics of Tr1 generation in the xeno-GvHD animal model and shows that treatment with an anti-MCT1 antibody suppresses proliferation in the effector phase. Figures 49A-B contain experimental data relating to the ex vivo culture of Tr1 lymphocytes with various antibodies, cytokines and ligands. The observed results indicate that anti-TIGIT and PVR ligands did not improve survival. In contrast, treatment with IL-2, IL-17 and IL-15 increased the ex vivo survival of Tr1 lymphocytes substantially (up to about 75% survival) in a dose-dependent manner. Figures 50A-B contain experimental data showing the effects of the small molecule MCT1 inhibitor on ketosis after 8-24 hours of starvation conditions based on blood glucose and ketone levels. Figures 51A-B contain experimental data showing that the small molecule MCT1 inhibitor does not trigger ketoacidosis after 24 hours of starvation and only causes a minimal reduction in pH (about 0.05) compared to starvation in the absence of the ketoacidosis. small molecule MCT1 inhibitor. Figure 52 shows the human MCT1 residues constituting the predicted epitope bound by 4 exemplary anti-human MCT1 antibodies according to the invention as determined by alanine scanning. The results show that the epitope bound by the 4 zncAan / nznz / q / Yi antibodies comprises the same extracellular region of human MCT1 and substantially the same residues of human MCT1. Figures 53 and 54 further map the specific residues of human MCT1 constituting the predicted epitope bound by 4 human anti-MCT1 antibodies according to the invention as determined by alanine scanning. Again, these results show that the epitope bound by all 4 antibodies comprises the same extracellular region of human MCT1 and substantially the same residues of human MCT1. Figure 55 contains experimental results indicating an anti-human MCT1 antibody according to the invention further binding to mouse MCT1 protecting transfectants expressing mouse MCT1 from the toxic effects of bromopyruvate. DETAILED DESCRIPTION OF THE INVENTION The present invention relates to antibodies and antigen-binding fragments thereof that bind to monocarboxylate transporter 1 (MCT1), nucleic acids encoding said anti-MCT1 antibodies and antigen-binding fragments thereof, compositions comprising said antibodies anti-MCT1 and antigen binding fragments thereof, and methods of using said anti-MCT1 antibodies, antibody fragments and compositions in diagnosis and treatment. Target antibody: MCT1 MCT1 is a multistep transmembrane protein responsible for the facilitated transport of key metabolites, including the products of glycolysis. The subject application provides novel anti-MCT1 antibodies, particularly human anti-MCT1 antibodies, including those comprising the same CDRs as any of the antibodies identified in this application as Ab1Ab83. Prior to the present invention, anti-MCT1 antibodies or antibody fragments that block MCT1 function have not been reported. Binding of an anti-MCT1 antibody or antibody fragment to MCT1 according to the invention will reduce, abolish, decrease or otherwise inhibit at least one of the functions of MCT1. As far as immunity is concerned, this binding and inhibition of MCT1 may have at least a suppressive effect on autoimmunity, eg, activated T cells, B cells and / or expression of inflammatory cytokines. Importantly, MCT1 is the only immunologically relevant lactate transporter expressed on T and B lymphocytes. The anti-MCT1 antibodies of the invention particularly target activated T lymphocytes due to a switch to glycolysis during lymphocyte activation. T effectors, thus providing an innovative and powerful opportunity to control autoimmune, inflammatory and allergic conditions. As demonstrated in the Examples, the anti-MCT1 antibodies of the invention provide selective inhibition of lymphocyte metabolism and an attractive safety profile, especially in light of the data on MCT1 deficiency in humans. Blocking lymphocyte glycolysis in inflammatory disease models, for example, disease-prone mouse models of lupus, prevents zncRan / nznz / q / Yi IFNγ production in these models and provides further evidence that antibodies Inventive agents that block lymphocyte glycolysis in a safe and effective manner have powerful potential as immunoregulatory drugs. Anti-MCT1 antibodies that block or inhibit MCT1 functions can be used to reduce autoimmunity. In particular, these antibodies can be used to suppress unwanted human immune responses such as autoimmune, allergic, lupus, GVHD, sepsis, or undesirable inflammatory inflammatory immune responses. MCT1 expression has also been implicated in cancers, due to the particular energy requirements and glycolysis dependence of tumor cells. The antibodies of the invention and their antigen-binding fragments are therefore suitable for the treatment of cancer. MCT1 overexpression in beta cells is also an underlying cause of exercise-induced hyperinsulinism (EIHI), so the antibodies of the invention can also be applied to the treatment of EIHI. Notably, while small molecule inhibitors of MCT proteins have been associated with toxicities to the retina, heart, and testis in preclinical models, MCT1-deficient humans have no toxicity to any of these organs (REF. 49 and Examples ), which supports the strong safety profile of the MCT1-specific antibodies of the invention. Furthermore, MCT1-deficient individuals have been shown to be healthy, and these conclusions are supported by the data in the examples, which show that MCT1 is not involved in human RBC lactate transport. Human MCT1 has the following amino acid sequence (SEQ ID NO: 1), deposited in the UniProt database under the identifier P53985-1: SEQ ID NO:1 MPPAVGGPVGYTPPDGGWGWAVVIGAFISIGFSYAFPKSITVFFKEIEGIFHATTSEVSWISSIMLA VMYGGGPISSILVNKYGSRIVMIVGGCLSGCGLIAASFCNTVQQLYVCIGVIGGLGLAFNLNPALTMIGKYF YKRRPLANGLAMAGSPVFLCTLAPLNQVFFGIFGWRGSFLILGGLLLNCCVAGALMRPIGPKPTKAGKDKS KASLEKAGKSGVKKDLHDANTDLIGRHPKQEKRSVFQTINQFLDLTLFTHRGFLLYLSGNVIMFFGLFAPLV FLSSYGKSQHYSSEKSAFLLSILAFVDMVARPSMGLVANTKPIRPRIQYFFAASVVANGVCHMLAPLSTTY VGFCVYAGFFGFAFGWLSSVlFETLMDLVGPQRFSSAVGLVTIVECCPVlLGPPLLGRLNDMYGDYKYTY WACGVVlIISGIYLFIGMGINYRLLAKEQKANEQKKESKEEETSIDVAGKPNEVTKAAESPDQKDTDGGPKE EESPV Binding to MCT1 and inhibition of MCT1 function An anti-MCT1 antibody of the invention may have any suitable affinity and / or avidity for MCT1. Affinity refers to the binding strength of an anti-MCT1 antibody or other antigen-binding protein to an epitope or antigenic determinant. Typically, affinity is measured in terms of a dissociation constant Kd defined as [Ab]x[Ag] / [Ab-Ag] where [Ab-Ag] is the molar concentration of the antibody-antigen complex, [Ab] is the molar concentration of unbound antibody and [Ag] is zncRan / nznz / q / Yi the molar concentration of unbound antigen. The affinity constant Ka is defined by 1 / Kd. Suitable methods for determining binding peptide specificity and affinity by competitive inhibition, equilibrium dialysis, and the like can be found, for example, in Harlow, et al., Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor. , NY, 1988); Colligan et al., Eds., Current Protocols in Immunology, Greene Publishing Assoc. and Wiley Interscience, NY, (1992, 1993), and Muller, Meth. Enzymol. 92:589-601 (1983). Affinity can be determined by any of the methods described elsewhere herein or their art-known equivalents. An example of a method that can be used to determine affinity is provided in the Scatchard test of Munson & Pollard, Anal. Biochem. 107:220 (1980). Binding affinity can also be determined by KINEXA, equilibrium methods (eg, enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA)) or kinetic analysis (eg, BIAcore™ assay). In yet another embodiment of the invention, anti-MCT1 antibodies and antigen-binding fragments, eg, human, humanized or chimerized anti-MCT1 antibodies or antibody fragments, can bind to MCT1 with a binding affinity ( Kd) less than or equal to 5χ105Μ, 10'5Μ, 5χ10'6M, 10'6Μ, 5χ107Μ, 10'7Μ, 5χ10'8Μ, 10'8Μ, 5x10'9Μ, 10'9Μ, 5χ1Ο'10, 10- 10, 5x10-11, 10nΜ, 5χ10-12, 10-12Μ, 5χ10-13Μ, or 10'13M, for example, as determined by ELISA, biolayer interferometry (BLI), KINEXA, or surface plasmon resonance a 25° or 37°C. Typically, an anti-MCT1 antibody provided by the invention has an affinity for MCT1 in the range of about 10-4 to about 10-12M (eg, about 10-7 to about 10-10M). The term "immunoreaction" herein typically refers to the binding of an anti-MCT1 antibody to MCT1 with an affinity of less than about 10 -4M. For example, in one particular aspect, the invention provides an anti-MCT1 antibody having a binding affinity (Kd) of about 7 x 10 -9M or less with respect to MCT1, as determined by, for example, KINEXA. In addition, anti-MCT1 antibodies and antigen-binding fragments, eg, human, humanized or chimerized anti-MCT1 antibodies or antibody fragments, of the invention may include anti-MCT1 antibodies or antibody fragments that bind to MCT1. with a dissociation constant (kotf) of less than or equal to 5x10'4s4, 10-4s-1, 5x10'5s4, or 10-5s-1. Avidity refers to the overall strength of the total interactions between a binding protein and an antigen (eg, the total strength of the interactions between an anti-MCT1 antibody and an MCT1). Affinity is the strength of the total non-covalent interactions between a single antigen-binding site on an antibody or other binding peptide and a single epitope or antigenic determinant. Avidity is generally governed by three main factors: the intrinsic affinity of the binding protein for the epitope or antigenic determinants to which it binds, the valence of the antibody or binding protein, and the antigen (for example, an antimicrobial antibody). -MCT1 with a valence of three, four or more will typically exhibit higher levels of avidity for an antigen than a bivalent antibody, and a bivalent antibody may have higher avidity for an antigen than a univalent antibody, especially when there are repeated epitopes on the antigen ), and / or the geometric arrangement of the interacting zncRan / nznz / q / Yi components. Avidity is generally measured by the same type of techniques used to assess affinity. Anti-MCT1 antibodies can be characterized based on their ability to bind to MCT1 and thus inhibit one or more functions of MCT1. Said anti-MCT1 antibodies can be used directly as therapeutic agents in a native form. Inhibitory anti-MCT1 antibodies can partially or fully inhibit various functions of MCT1, such as the transport of monocarboxylates, ions, and other molecules, eg, toxins. In a particular embodiment, the antibodies of the invention inhibit MCT 1-mediated lactate transport. The inhibition can be measured by any suitable method. In one aspect, the inhibition is reflected in the inhibitory anti-MCT1 antibody causing at least about 20%, eg, at least about 30%, at least about 40%, at least about 50%, at least about about 60%, at least about 75% or more (eg, about 25-100%) decrease in MCT1-mediated lactate transport. The percentage decrease in this aspect can be determined when considering the effect of anti-MCT1 antibodies on lactate transport compared to controls, for example, in comparison with the results of lactate transport assays of cells that they do not express MCT1 or cells not blocked by the antibody. Production of anti-MCT1 antibodies Anti-MCT1 monoclonal antibodies (mAbs) and antigen-binding fragments according to the present invention can potentially be produced by different methods such as monoclonal antibody methodology, for example, the standard Kohler somatic cell hybridization technique and Milstein (1975) Nature 256:495. Other techniques for producing monoclonal antibodies may also be used, for example, viral or oncogenic transformation of B cells. A preferred animal system for preparing hybridomas is the murine system. Hybridoma production in the mouse is a well-established process. Immunization protocols and techniques for isolating immunized splenocytes for fusion purposes are known in the art. Fusion components (eg murine myeloma cells) and fusion procedures are also known. Chimeric or humanized antibodies of the present invention can be prepared based on the sequence of a murine monoclonal antibody prepared as described above. DNA encoding the heavy and light chain immunoglobulins can be obtained from the murine hybridoma of interest and engineered to contain non-murine (eg, human) immunoglobulin sequences by standard molecular biology techniques. For example, to create a chimeric antibody, murine variable regions can be ligated to human constant regions by methods known in the art (see, eg, US Patent No. 4,816,567 to Cabilly et al.). To create a humanized antibody, murine CDR regions can be inserted into a human framework by methods known in the art (see, for example, US Patent No. 5,225,539 to Winter, and US Patent Nos. 5,530,101 ; 5,585,089; 5,693,762 and 6,180,370 from Queen et zncRan / nznz / q / Yi al.). According to at least some embodiments of the invention, the antibodies are human monoclonal antibodies. Such human monoclonal antibodies directed against MCT1 can be generated with the use of transgenic or transchromosomal mice that carry parts of the human immune system instead of the mouse system, eg, HuMAb Mouse™, KM Mouse™ (see, eg, Lonberg, et al (1994) Nature 368 (6474): 856-859). Consequently, mice exhibit reduced expression of mouse IgM or K and in response to immunization, the introduced human heavy and light chain transgenes switch class and somatic mutation to generate monoclonal high-affinity human IgG K (Lonberg, N. et al (1994), supra, discussed in Lonberg, N. (1994) Handbook of Experimental Pharmacology 113:49-101, Lonberg, N. and Huszar, D. (1995) Intern Rev Immunol 13:65 -93, and Harding, F. and Lonberg, N. (1995) Ann. N. Y. Acad. Sel. 764:536-546). In another embodiment, human antibodies according to at least some embodiments of the invention may be obtained by using a mouse that has human immunoglobulin sequences in transgenes and transchromosomes, such as a mouse that has a transgene of human heavy chain and a human light chain transchromosome. Such mice, referred to herein as KM mice, are described in detail in PCT publication WO 02 / 43478 to Ishida et al. Likewise, alternative transgenic animal systems expressing human immunoglobulin genes are available in the art and can be used to generate anti-MCT1 antibodies in accordance with at least some embodiments of the invention. For example, an alternative transgenic system called Xenomouse (Abgenix, Inc.) can be used; such mice are described in, for example, US Patent Nos. 5,939,598, 6,075,181, 6,114,598, 6,150,584, and 6,162,963 to Kucherlapati et al. In addition, alternative animal transchromosomal systems expressing human immunoglobulin genes are available in the art and can be used to generate anti-MCT1 antibodies in accordance with at least some embodiments of the invention. For example, mice having a human heavy chain transchromosome and a human light chain transchromosome, called TC mice, can be used; which are described in Tomizuka et al. (2000) Proc. nati. Acad Sel. USA 97:722-727'. In addition, cows carrying human heavy and light chain transchromosomes have been described in the art (Kuroiwa et al. (2002) Nature Biotechnology 20: 889-894) and can be used to generate anti-MCT1 antibodies according to at least Some embodiments of the invention. Human monoclonal antibodies according to at least some embodiments of the invention may also be prepared via phage display methods to screen human immunoglobulin gene libraries. These phage display methods for isolating human antibodies have been established in the state of the art. See, for example: US Patent Nos. 5,223,409; 5,403,484; and 5,571,698 from Ladner et al.; Patent Nos. 5,427,908 and 5,580,717 to Dower et al.; Patent Nos. 5,969,108 and 6,172,197 to McCafferty et al.; and US Patent Nos. 5,885,793; 6,521,404; 6,544,731; 6,555,313; 6,582,915 and 6,593,081 from Griffiths et zncRan / nznz / q / YiAi al. Human monoclonal antibodies according to at least some embodiments of the invention can also be prepared using SCID mice in which the human immune cells have been reconstituted so that a human antibody response can be generated upon immunization. Such mice are described in, for example, US Patent Nos. 5,476,996 and 5,698,767 to Wilson et al. In some embodiments, human Ig mice are used to generate human anti-MCT1 antibodies according to the invention, for example, by immunizing said mice with a purified or enriched preparation of recombinant MCT1 and / or MCT1 antigen, or MCT1 fusion protein, as described in Lonberg, N. and et al. (1994) Nature 368 (6474): 856-859; Fishwild, D. and et al. (1996) Nature Biotechnology 14: 845-851; and PCT publication WO 98 / 24884 and WO 01 / 14424. Preferably, the mice will be 6-16 weeks old after the first infusion. For example, a purified or recombinant (dosage ranging from 5-500 pg) preparation of MCT1 antigen can be used to immunize mice with human Ig intraperitoneally. In general, transgenic mice respond when initially immunized intraperitoneally (IP) with antigen in complete Freund's adjuvant, followed by IP immunizations (up to a total of 6) with antigen in incomplete Freund's adjuvant every two weeks. However, other non-Freund's adjuvants are also effective. Furthermore, whole cells in the absence of adjuvant are found to be highly immunogenic. The immune response can be monitored over the course of the immunization protocol with plasma samples obtained by retroorbital bleeds. Plasma can be selected by ELISA, and mice with sufficient titers of human anti-MCT1 immunoglobulin can be used for fusions. Mice can be boosted with antigen intravenously 3 days before being sacrificed and having their spleens removed. It is expected that 2-3 fusions may need to be performed for each immunization. In general, between 6 and 24 mice are immunized for each antigen. In certain embodiments, hybridomas producing an anti-MCT1 human monoclonal antibody according to the invention can be generated using splenocytes and / or lymph node cells from immunized mice that are isolated and fused to an appropriate immortalized cell line, such as a mouse myeloma cell line. The resulting hybridomas can be screened for the production of antigen-specific antibodies. In certain embodiments, an anti-MCT1 antibody according to the invention may be produced in a host cell transfectoma through, for example, a combination of recombinant DNA techniques and gene transfection methods known in the art. technique (eg Morrison, S. (1985) Science 229: 1202). For example, to express the antibodies, or antibody fragments thereof, DNA encoding partial or full-length heavy and light chains can be obtained by standard molecular biology techniques (for example, PCR amplification or cDNA cloning using the using a hybridoma expressing the antibody of interest), and the DNAs can be inserted into expression vectors such that the zncRan / nznz / q / YiAi genes are operably linked to transcriptional and translational control sequences. In this context, the term "operably linked" means that an antibody gene is linked to a vector in such a way that the transcriptional and translational control sequences within the vector fulfill their intended function of regulating the transcription and translation of the antibody gene. The expression vector and expression control sequences are chosen to be compatible with the expression host cell being used. The antibody light chain gene and the antibody heavy chain gene can be inserted into separate vectors or, more generally, both genes are inserted into the same expression vector. The antibody genes are inserted into the expression vector by standard methods (eg, ligation of complementary restriction sites on the antibody gene fragment and vector, or broken-end ligation if no restriction site is present). The heavy and light chain variable regions of the antibodies described herein can be used to create full-length antibody genes of any antibody isotype by inserting them into expression vectors that already encode heavy chain constant regions and constant regions. of the desired isotype, such that the Vh segment is operatively linked to the Ch segment in the vector and the Vl segment is operatively linked to the Cl segment in the vector. Additionally or alternatively, the recombinant expression vector can encode a signal peptide that facilitates secretion of the antibody chain from a host cell. The antibody chain gene can be cloned into the vector such that the signal peptide is ligated in frame to the amino terminus of the antibody chain gene. The signal peptide can be an immunoglobulin signal peptide or a heterologous signal peptide (ie, a signal peptide from a non-immunoglobulin protein). In some cases, antagonistic anti-MCT1 antibodies can be obtained by immunizing animals, eg, a non-human mammal, non-human primate, bird, or amphibian; eg, a Macaca fascicularis, rodent, rabbit, guinea pig, bovine, equine, canine, feline, chicken, frog, with virus-like particles (VLPS) expressing on their surface an intact MCT1 protein, MCT1 fragment, MCT1 fusion protein or MCT1 multimer and optionally another adjuvant. The use of VLPs expressing an antigen as immunogens to generate a cellular or humoral immune response (antibody) to an antigen expressed on the surface of the VLP is known in the art. (Ver, por ejemplo, de la patente estadounidense N.° 10,138,277; 10,130,696; 10,125,175; 10,086,056; 10,080,796; 10,072,058; 10,046,026; 10,040,830; 9,969,986; 9,957,300; 9,833,504; 9,803,189; 9,637,532; 9,566,327; 9,617,321; 9,585,954; 9,518,096; 9,517,261; 9,381,239 ;9,481,875;9,213,027;9,296,792;9,216,229; 8,980,275; 8,889,144; 8,852,604; 8,728,985; 8,691,209; 8,680,244; 8,574,590; 8,529,906; 8,324,149; 8,377,691; 8,158,130; 7,959,928; 7,875,450; 7,641,896; 7,494,656; 7,479,280; 7,320,793; 7,264,810; 7,229,624; 7,138,252; 6,991,795; 6,964,769; 6,534,064 and 5,667,782 among others, which patents are incorporated herein by reference in their entirety). Expression of anti-MCT1 antibodies A suitable host cell generally includes any cell in which the subject zncRan / nznz / q / Yi anti-MCT1 antibodies and their antigen-binding fragments can be produced recombinantly by readily available techniques and materials. For example, the anti-MCT1 antibodies and their antigen-binding fragments of the present invention can be produced in genetically engineered host cells according to conventional techniques. Suitable host cells are those cell types that can be transformed or transfected with exogenous DNA and grown in culture, and include bacteria, fungal cells (eg, yeast), and cultured higher eukaryotic cells (including cultured cells of multicellular organisms), particularly cells cultured mammalian cells, eg, human or non-human mammalian cells. In an exemplary embodiment, these antibodies can be expressed in CHO cells or HEK-293 cells. Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press (1989), and Current Protocol in Molecular Biology, Ausubel et al., eds., New York, NY: Green and Wiley and Sons (1993) describe techniques for manipulating cloned DNA molecules and introducing exogenous DNA into a variety of host cells. In some exemplary embodiments, the antibodies can be expressed in mating competent yeast, eg, any haploid, diploid, or tetraploid yeast that can grow in culture. Yeast useful in fermentation expression methods may exist in a haploid, diploid, or other polyploid form. Cells of a given ploidy can, under appropriate conditions, proliferate for an indefinite number of generations in that way. Diploid cells can also sporulate to form haploid cells. Sequential mating can result in tetraploid strains through further mating or fusion of diploid strains. The present invention contemplates the use of haploid yeast, as well as diploid or other polyploid yeast cells produced, for example, by spheroplast mating or fusion. By way of example, said yeast may include members of the family Saccharomycetaceae, which includes the genera Arxiozyma; Ascobotñozima; Cyteromyces; Debaryomyces Dekkera Eremothecium; Issatchenkia; Kazachstania Kluyveromyces; Kodamaea; Lodderomyces; pachysolen; Pichia Saccharomyces; Saturnispore; Tetrapisispore; Torulaspora; Williopsis and Zygosaccharomyces. Other types of yeast potentially useful in the invention include Yarrowia; Rhodosporidium; Candida Hansenula; phyllobasium; Sporidiobol; Bullera Leucosporidium and Filobasidella. The coding sequence for the polypeptide of interest is operably linked to transcriptional and translational regulatory sequences that provide for expression of the polypeptide in the desired host cells, eg, yeast or mammalian cells. These vector components may include, but are not limited to, one or more of the following: an enhancer element, a promoter, and a transcription termination sequence. Sequences for secretion of the polypeptide, eg, a signal sequence, and the like, may also be included. An origin of replication, eg, a yeast origin of replication, is optional, as expression vectors often integrate into the host cell genome. In one embodiment of the invention, the polypeptide of interest is operably linked or fused to sequences that provide for optimized secretion of the polypeptide from diploid yeast cells. zncRan / nznz / q / Yi Promoters are non-translated sequences located upstream (5') of the start codon of a structural gene (generally within about 100 to 1000 bp) that control the transcription and translation of particular nucleic acid sequences to which they are operatively linked. . Such promoters are divided into several classes: inducible, constitutive, and repressible promoters (which increase transcription levels in response to the absence of a repressor). Inducible promoters can initiate increased levels of DNA transcription under their control in response to some change in culture conditions, for example, the presence or absence of a nutrient or a change in temperature. The promoter fragment may also serve as the site for homologous recombination and integration of the expression vector at the same site in the host cell, eg, yeast or mammalian cell genome; Alternatively, a selectable marker can be used as the site for homologous recombination. Anti-MCT1 antibody polypeptides of interest can be recombinantly produced not only directly, but also as a fusion polypeptide with a heterologous polypeptide, eg, a signal sequence or another polypeptide having a specific cleavage site at the terminus. N of the mature protein or polypeptide. In general, the signal sequence may be a component of the vector, or it may be part of the coding sequence for the polypeptide that is inserted into the vector. The selected heterologous signal sequence, for example, is one that is recognized and processed via one of the standard pathways available within the host cell, eg, a mammalian cell, insect cell, or yeast cell. Furthermore, these signal peptide sequences can be engineered to provide enhanced secretion in expression systems. Secretion signals of interest also include mammalian and yeast signal sequences, which may be heterologous to the protein being secreted, or may be a sequence native to the protein being secreted. Signal sequences include prepeptide sequences, and in some cases may include propeptide sequences. Many of these signal sequences are known in the art, including signal sequences found in immunoglobulin chains, eg, K28 preprotoxin sequence, PHA-E, FACE, human MCP-1, serum albumin signal sequences. human, human Ig heavy chain, human Ig light chain, and the like. For example, see Hashimoto et al., Protein Eng., 11(2):75 (1998); and Kobayashi et al., Therapeutic Apheresis, 2(4):257 (1998). Transcription can be increased by inserting a transcriptional activator sequence into the vector. These activators are cis-acting elements of DNA, generally around 10 to 300 bp, that act on a promoter to increase its transcription. Transcription enhancers are relatively orientation and position independent, having been found 5' and 3' to the transcription unit, within an intron, as well as within the coding sequence itself. The enhancer can be spliced ​​into the expression vector at a position 5' or 3' to the coding sequence, but is, for example, located at a site 5' to the promoter. Expression vectors used in eukaryotic host cells may also contain zncRan / nznz / q / Yi sequences necessary for the termination of transcription and to stabilize the mRNA. Such sequences are commonly available from 3' to the translation stop codon, in untranslated regions of eukaryotic or viral DNA or cDNA. These regions contain segments of nucleotides transcribed as polyadenylated fragments in the untranslated portion of the mRNA. Construction of suitable vectors containing one or more of the components listed above employs standard ligation techniques or PCR / recombination methods. The isolated plasmids or DNA fragments are cut, tailored and religated in the desired fashion to generate the required plasmids or by recombinant methods. For analysis to confirm the correct sequences in the constructed plasmids, the ligation mixtures are used to transform host cells and successful transformants are selected for resistance to antibiotics (eg, ampicillin or zeocin) where appropriate. Plasmids from transformants are prepared, analyzed by restriction endonuclease digestion, and / or sequenced. As an alternative to restriction and ligation of fragments, recombination methods based on specific binding sites (att) and recombination enzymes can be used to insert DNA sequences into a vector. Such methods are described, for example, by Landy, Ann. Rev. Biochem., 58: 913-949 (1989); and they are known by people in the mid-level trade. Such methods use intermolecular DNA recombination mediated by a mixture of lambda and E. coli-encoded recombination proteins. Recombination occurs between att sites on the interacting DNA molecules. For a description of att sites, see Weisberg and Landy, Site-Specific Recombination in Phage Lambda, in Lambda II, p. 21 1-250, Cold Spring Harbor, NY: Cold Spring Harbor Press (1983). The DNA segments flanking the recombination sites are changed so that after recombination, the att sites are hybrid sequences composed of sequences donated by each parental vector. Recombination can occur between DNA of any topology. The att sites can be introduced into a sequence of interest by ligating the sequence of interest into an appropriate vector; generating a PCR product containing att B sites by using specific primers; generating a cDNA library cloned into an appropriate vector containing att sites; and the like. Folding, as used herein, refers to the three-dimensional structure of polypeptides and proteins, where interactions between amino acid residues act to stabilize the structure. Although non-covalent interactions are important in determining structure, generally the proteins of interest will have intramolecular and / or intermolecular covalent disulfide bridges formed by two cysteine ​​residues. For natural or derived proteins and polypeptides and variants thereof, the proper folding is typically the arrangement that results in optimum biological activity, and can be conveniently monitored by activity assays, eg, ligand binding, enzymatic activity, etc. In some cases, for example, where the desired product is of synthetic origin, tests that are based on biological activity will be less meaningful. The proper folding of such molecules can be determined based on physical properties, energy considerations, zncRan / nznz / q / Yi modeling studies, and the like. The expression host can be further modified by introducing sequences encoding one or more enzymes that enhance folding and disulfide bond formation, ie, foldases, chaperonins, protein disulfide isomerases, etc. Said sequences can be expressed constitutively or inducibly in the yeast host cell, through the use of vectors, markers, etc. as known in the art. Preferably, the sequences, which include sufficient transcriptional regulatory elements for the desired part of expression, are stably integrated into the host cell genome through a targeted methodology. For example, the eukaryotic protein disulfide isomerase (PDI) is not only an efficient catalyst of protein cysteine ​​oxidation and disulfide bond isomerization, but also exhibits chaperone activity. PDI coexpression can facilitate the production of active proteins that have multiple disulfide bridges. Also of interest is the expression of the immunoglobulin heavy chain binding protein (BIP); cyclophilin; and the like. In one embodiment of the invention, each of the haploid parental strains expresses a different folding enzyme, for example, one strain may express BIP, and the other strain may express PDI or combinations thereof. Cultured mammalian cells are also preferred exemplary hosts for the production of the described anti-MCT1 antibodies and their antigen-binding fragments. As mentioned, CHO cells are particularly well suited for antibody expression. Many procedures are known in the art for making monoclonal antibodies in mammalian cells. (See, Galfre, G. and Milstein, C, Methods Enzym., 73:3-46, 1981; Basalp et al., Turk. J. Biol, 24: 189-196, 2000; Wurm, FM, Nat. Biotechnol , 22: 1393-1398, 2004; and Li et al., mAbs, 2 (5): 466-477, 2010). As mentioned in more detail below, common host cell lines employed in mammalian monoclonal antibody manufacturing schemes include, among others, the human embryonic retinoblast cell line PER.C6® (Crucell NV, Leiden, The Netherlands), NSO (Medical Research Council, London, UK) murine myeloma cells, CV1 monkey kidney cell line, 293 human embryonic kidney cell line, BHK baby hamster kidney cell line, VERO African green monkey kidney cell line , HELA human cervical carcinoma cell line, MDCK canine kidney cells, BRL rat buffalo liver cells, W138 human lung cells, HepG2 human liver cells, MMT mouse mammary tumor cells, TRI cells, MRC5 cells, cells Fs4, myeloma or lymphoma cells, or Chinese hamster ovary (Cricetulus griseus) CHO cells, and the like. Many different subclones or subcellular lines of CHO cells are known in the art to be useful and optimized for the production of recombinant monoclonal antibodies, such as the DP12 (CHO Kl dhfr-) cell line. NSO cells are a subclone of NS-1 cells that do not secrete Ig and do not synthesize light chains that are resistant to azaguanine. Other Chinese hamster cells and CHO cells are commercially available (from ATCC etc.), including CHO-DXB11 (CHODUKX), CHO-pro3, CHO-DG44, CHO 1-15, CHO DP-12, Lec2, M1WT3, Lec8, pgsA-745, and the like, all of which are genetically altered to optimize the cell line for various parameters. zncRan / nznz / q / Yi Monoclonal antibodies are commonly made using a feed-batch method whereby monoclonal antibody chains are expressed in a mammalian cell line and secreted into tissue culture medium in a bioreactor. Medium (or feed) is continuously supplied to the bioreactor to maximize recombinant protein expression. The recombinant monoclonal antibody is then purified from the collected media. In some circumstances, additional steps are needed to reassemble the antibodies through reduction of disulfide bonds, etc. Such production methods can be scaled up to be as large as 10,000 L in a single batch or more. It is now routine to obtain up to 20 pg / cell / day using such cell lines and methodologies, providing titers up to 10 g / L or higher, amounting to 15 to 100 kg of 10 kL to 25 kL bioreactors. (Li et al, 2010). Various details of this production methodology are provided below, including cloning the polynucleotides encoding the antibodies into expression vectors, transfecting cells with these expression vectors, selecting transfected cells, and expressing and purifying recombinant monoclonal antibodies from these cells. For recombinant production of an anti-MCT1 antibody or antigen-binding fragment in mammalian cells, the nucleic acids encoding the antibody or fragment thereof are generally inserted into a replicable vector for further cloning (DNA amplification) or for further cloning. The expression. The DNA encoding the antibody is readily isolated or synthesized by conventional procedures (eg, with the use of oligonucleotide probes that are capable of binding specifically to the DNAs encoding the heavy and light chains of the antibody). Vector components generally include, but are not limited to, one or more of the following: a signal sequence, an origin of replication, one or more marker genes, an enhancer element, a promoter, and a transcription termination sequence. . The selection of promoters, terminators, selectable markers, vectors, and other elements is a matter of routine design for the mid-level tradesman. Many of these elements are known in the art and are available from commercial vendors. The antibodies of this invention can be recombinantly produced not only directly, but also as a fusion polypeptide with a heterologous polypeptide, which is, for example, a signal sequence or another polypeptide having a specific N-terminal cleavage site. of the mature protein or polypeptide. The selected homologous or heterologous signal sequence, for example, is one that is recognized and processed (ie, cleaved by a signal peptidase) by the host cell. In mammalian cell expression, mammalian signal sequences are available, as are viral secretory leaders, eg, the herpes simplex gD signal. Such expression vectors and cloning vectors will generally contain a nucleic acid sequence that allows the vector to replicate in one or more selected host cells. Typically, in cloning vectors, this sequence is one that allows the vector to replicate independently of host chromosomal DNA, and includes origins of replication or autonomously replication sequences. Such sequences are well known from a variety of bacteria, yeasts and viruses, for example, the origin of replication plasmid pBR322 is suitable for most zncRan / nznz / q / Yi Gram-negative bacteria, the origin of plasmid 2mu is suitable for yeast and various viral origins (simian virus 40 (SV40), polyoma, adenovirus, vesicular stomatitis virus (VSV) or bovine papillomavirus (BPV)) are useful for vector cloning in mammalian cells. In general, the origin of replication component is not required for mammalian expression vectors (the SV40 origin can generally be used only because it contains the early promoter). These vectors will also typically contain a selection gene, also called a selectable marker. Typical selectable genes encode proteins that (a) confer resistance to antibiotics or other toxins, eg, ampicillin, neomycin, methotrexate, or tetracycline, (b) complement auxotrophic deficiencies, or (c) provide critical nutrients that are not available in complex media. eg the gene encoding D-alanine racemase for Bacilli. An example of a selection scheme uses a drug to arrest the growth of a host cell. Drug selection is generally used to select for cultured mammalian cells into which foreign DNA has been inserted. Such cells are commonly referred to as transfectants. Cells that have been grown in the presence of the selective agent and can transmit the gene of interest to their progeny are called stable transfectants. Examples of such dominant selection use the drugs neomycin, mycophenolic acid, and hygromycin. An exemplary selectable marker is a gene encoding resistance to the antibiotic neomycin. Selection is carried out in the presence of a neomycin-type drug, such as G-418 or the like. Those cells that are successfully transformed with a heterologous gene produce a protein that confers drug resistance and thus survives the selection regimen. Selection systems can also be used to increase the expression level of the gene of interest, a process called amplification. Amplification of transfectants generally occurs by culturing the cells in the presence of a low level of the selective agent and then increasing the amount of selective agent to select for cells that produce high levels of the introduced gene products. Exemplary selectable markers suitable for mammalian cells are those that allow the identification of cells competent to take up the antibody nucleic acid, such as dihydrofolate reductase (DHFR), thymidine kinase, metallothionein-1 and -II, for example, genes for primate metallothionein, adenosine deaminase, ornithine decarboxylase, etc. For example, an amplified selectable marker for mammalian cells is dihydrofolate reductase, which confers resistance to methotrexate. Other drug resistance genes (eg, hygromycin resistance, multidrug resistance, puromycin acetyltransferase) may also be used. Cells transformed with the DHFR selection gene are first identified by culturing all transformants in culture medium containing methotrexate (MTX), a competitive DHFR antagonist. A suitable host cell when using wild-type DHFR is the Chinese hamster ovary (CHO) cell line deficient in DHFR activity. Alternatively, host cells (particularly wild-type hosts containing endogenous DHFR) transformed or cotransformed with DNA sequences encoding the antibody, wild-type DHFR protein, and another selectable marker, such as aminoglycoside 3'zncAan / nznz / q / Yi phosphotransferase (ΑΡΗ), can be selected by growing cells in medium containing a selectable marker selection agent, such as an aminoglycosidic antibiotic, eg, kanamycin, neomycin or G-418. See US Patent No. 4,965,199. These vectors may comprise an enhancer sequence that facilitates the transcription of a DNA encoding the antibody. Many mammalian gene enhancer sequences are known (eg, globin, elastase, albumin, alpha-fetoprotein, and insulin). A frequently used enhancer is one derived from a eukaryotic cell virus. Examples of these include the SV40 enhancer at the late replication origin site (bp 100-270), the cytomegalovirus early promoter enhancer, the polyoma enhancer at the late replication origin site, and adenovirus enhancers (see, also Yaniv, Nature, 297: 17-18, 1982, on enhancer elements for activation of eukaryotic promoters). The enhancer can be spliced ​​into the vector at a position 5' or 3' to the antibody coding sequence, but is, for example, located at a site 5' to the promoter. Expression and cloning vectors will also generally comprise a promoter that is recognized by the host organism and is operably linked to the antibody nucleic acid. Promoter sequences are known from eukaryotes. Virtually all eukaryotic genes have an AT-rich region located approximately 25 to 30 bases upstream of the site where transcription begins. Another sequence found 70 to 80 bases upstream of the start of transcription of many genes is a CNCAAT region where N can be any nucleotide. At the 3' end of most eukaryotic genes, an AATAAA sequence is found which may be the signal for the addition of the poly A tail to the 3' end of the coding sequence. All such sequences are suitably inserted into eukaryotic expression vectors. Transcription of antibody vectors in mammalian host cells is controlled, for example, by promoters derived from the genomes of viruses, such as polyoma virus, avian diphtheria virus, adenovirus (such as adenovirus 2), BPV, sarcoma virus avian, cytomegalovirus, a retrovirus, hepatitis B virus, and mostly eg SV40, from heterologous mammalian promoters, eg the actin promoter or an immunoglobulin promoter, from heat shock promoters, provided such promoters are compatible with host cell systems. The SV40 virus early and late promoters are conveniently obtained as an SV40 restriction fragment that also contains the SV40 viral origin of replication. The human cytomegalovirus immediate early promoter is conveniently obtained as a HindIII E restriction fragment. A system for expressing DNA in mammalian hosts using BPV as a vector is described in US Patent No. 4,419,446. A modification of this system is described in US Patent No. 4,601,978. See also Reyes et al., Nature, 297: 598-601 (1982) on the expression of human beta-interferon cDNA in mouse cells under the control of a herpes simplex virus thymidine kinase promoter. Alternatively, the Rous sarcoma virus long terminal repeat can be used as the promoter. Strong transcriptional promoters can be used, such as promoters from SV40, zncRan / nznz / q / Yi cytomegalovirus or myeloproliferative sarcoma virus. See, for example, US Patent No. 4,956,288 and US Patent Publication No. 20030103986. Other suitable promoters include those from metallothionein genes (US Patent Nos. 4,579,821 and 4,601,978) and the adenovirus major late promoter. Expression vectors for use in mammalian cells include pZP-1, pZP-9, and pZMP21, which have been deposited at the American Type Culture Collection, 10801 University Blvd., Manassas, VA. United States with accession numbers 98669, 98668, and PTA-5266, respectively, and derivatives of these vectors. Expression vectors used in eukaryotic host cells (yeast, fungus, insect, plant, animal, human, or a nucleated cell of another multicellular organism) will generally also contain sequences necessary for the termination of transcription and for stabilizing the mRNA. In general, these sequences are available in the 5' and occasionally 3' untranslated regions of eukaryotic or viral DNA or cDNA. These regions contain segments of nucleotides transcribed as polyadenylated fragments in the untranslated portion of the mRNA encoding the antibody. One useful transcription termination component is the bovine growth hormone polyadenylation region. See WO 94 / 11026 and the expression vector disclosed therein. Host cells suitable for cloning or expressing the target antibodies include prokaryotic, yeast or higher eukaryotic cells described above. However, interest has been greatest in vertebrate cells, and propagation of vertebrate cells in culture has become a routine procedure. Examples of useful mammalian host cell lines are monkey kidney line CV1 transformed by SV40 (COS-1 (ATCC No. CRL 1650); and COS-7, ATCC CRL 1651); human embryonic kidney line (293 or 293 cells subcloned for growth in suspension culture, (ATCC No. CRL 1573; Graham et al., J. Gen. Virol, 36: 59-72 (1977)); kidney cells baby hamster (BHK, ATCC CCL 10, ATCC No. CRL 1632; BHK 570, ATCC No. CRL 10314); CHO cells (CHO-K1, ATCC No. CCL 61; CHO-DG44, Urlaub et al. , Proc. Nati. Acad. Sel. USA, 77: 4216-4220 (1980)); mouse Sertoli cells (TM4, Mather, Biol. Reprod., 23:243-251, 1980); monkey kidney cells (CV1 ATCC CCL 70), African green monkey kidney cells (VERO-76, ATCC CRL1587), human cervical carcinoma cells (HELA, ATCC CCL 2), canine kidney cells (MDCK, ATCC CCL 34); rat buffalo liver cells (BRL 3A, ATCC CRL 1442), human lung cells (W138, ATCC CCL 75), human liver cells (Hep G2, HB 8065), mouse mammary tumor (MMT 060562, ATCC CCL51) TRI cells (Mather et al., Annals N.Y Acad. Sci. 383:44-68 (1982)), MRC 5 cells, FS4 cells, and a hepatitis cell line. Human oma (Hep G2). Additional suitable cell lines are known in the art and are available from public repositories such as the American Type Culture Collection, Manassas, VA. Host cells are transformed with the above-described expression or cloning vectors for antibody production and cultured in conventional nutrient medium suitably modified to induce promoters, select transformants, or amplify genes encoding the desired sequences as discussed above. The mammalian host cells used to produce the zncAan / nznz / q / Yi antibody of this invention can be grown in a variety of media. Commercially available media such as Ham's F10 (SigmaAldrich Corporation, St. Louis, MO), Minimum Essential Medium ((MEM (Sigma-Aldrich Corporation, St. Louis, MO), Roswell Park Memorial Institute- 1640 medium ( RPMI-1640, Sigma- Aldrich Corporation, St. Louis, MO), and Dulbecco's modified Eagle's medium ((DMEM Sigma-Aldrich Corporation, St. Louis, MO) are suitable for culturing the host cells. In addition, any of the media described in Ham et al. , Meth. Era., 58:44 (1979); Barnes et al., Anal. Biochem., 102:255 (1980); US Pat. 03430; WO 87 / 00195; or Revised US Patent No. 30,985, can be used as a culture medium for host cells. Any of these media can be enriched, as needed, with hormones and / or other growth factors ( such as insulin, transferrin or epidermal growth factor), salts (such as sodium chloride, calcium, magnesium and phosphate), buffers (such as HEPES), nucleotides (such as adenosine and thymidine), antibiotics (such as the drug gentamicin), trace elements (defined as inorganic compounds usually present in final concentrations in the micromolar range), and glucose or a equivalent power source. Any other necessary supplements may also be included in appropriate concentrations that would be known to those of the mid-level trade. Culture conditions, such as temperature, pH, and the like, are those previously used with the host cell selected for expression, and will be apparent to the mid-level trade. Methods of development and optimization of culture media and conditions are known in the art. (See, Gronemeyer et al., Bioengineering, 1 (4): 188-212, 2014). After culture conditions are optimized and a preferred cell line clone is selected, these cells are grown (adherent cells or suspension cultures) most typically in a fed-batch process in a bioreactor (many models are commercially available). ) which involves continuously feeding the cell culture with medium and feed, optimized for the particular cell line chosen and selected for this purpose. (See, Butler, M., Appl. Microbiol. Biotechnol, 68:283-291, 2005; and Kelley, B., mAb, 1(5):443-452, 2009). Perfusion systems are also available where media and feed are continuously supplied to the culture while the same volume of media is withdrawn from the bioreactor. (Wurm, 2004). Synthetic media, also commercially available, are available for growing cells in fed-batch culture, avoiding the possibility of contamination from external sources, such as the use of animal components, such as bovine serum albumin, etc. . However, animal-free hydrolysates are commercially available to help increase cell density, culture viability, and productivity. (L¡etal., 2010). Many studies have been performed in an effort to optimize cell culture media, including careful attention to available headspace in roller bottles, redox potentials during the growth and expression phases, the presence of reducing agents to maintain disulfide bridges during production, etc. (See, for example, Hutterer et al., mAbs, 5(4):608-613, 2013; and Mullan et al., BMC Proceed., 5(Suppl 8):P110, 2011). Various methodologies have been developed to address the possibility of deleterious oxidation during zncAan / nznz / q / Yi production of recombinant monoclonal antibodies. (See, for example, US Patent No. 8,574,869). Cultured cells can be grown by feeding nutrients continuously or as separately administered amounts. Often, various process parameters such as cell concentration, pH, temperature, CO2, d02, osmolality, the amount of metabolites such as glucose, lactate, glutamine and glutamate, and the like, are monitored through the use of probes during cell growth either online by direct connection to calibrated analyzers or offline by operator intervention. The culturing step also typically involves ensuring that cells grown in culture maintain the transfected recombinant genes by any means known in the art for cell selection. After fermentation, i.e., upon reaching maximum cell growth and recombinant protein expression, the culture step is typically followed by a harvest step, whereby the cells are separated from the medium and thus a sample is obtained. harvested cell culture medium. (See, Liu et al., mAbs, 2(5):480-499, 2010). Typically, several purification steps, involving column chromatography and the like, follow cultivation to separate the recombinant monoclonal antibody from cell components and cell culture medium components. The exact purification steps required for this phase of recombinant monoclonal antibody production depend on the site of expression of the proteins, i.e., in the cytosol of the cells themselves, or the most commonly preferred route of protein excreted into the culture medium. cell phone. Various cellular components can be separated using techniques known in the art, such as differential centrifugation techniques, gravity-based cell settlement, and / or size exclusion chromatography / filtration techniques which may include tangential flow microfiltration or deep filtration. . (See, Pollock et al., Biotechnol. Bioeng., 110: 206-219, 2013, and Liu et al., 2010). Centrifugation of cellular components can be accomplished on a large scale by the use of continuous disc centrifuges followed by clarification with depth and membrane filters. (See Kelley, 2009). Very often, after clarification, the recombinant protein is further purified by protein A chromatography due to the high affinity of protein A for the Fe domain of antibodies, and this usually occurs by using a chromatography elution step. Low pH / acidification (typically the acidification step is combined with a preventative virus inactivation step). Flocculation and / or precipitation steps by acidic or cationic polyelectrolytes can also be used to separate animal cells in suspension cultures of soluble proteins. (Liu et al., mAbs, 2(5):480-499, 2010). Finally, anion and cation exchange chromatography, hydrophobic interaction chromatograph (HIC), hydrophobic charge induction chromatograph (HCIC), hydroxyapatite chromatography with ceramic hydroxyapatite (Cas(PO4)3OH)2, and combinations of these techniques are typically used to polish the recombinant monoclonal antibody solution. The final formulation and concentration of the desired monoclonal antibody can be achieved through the use of ultracentrifugation techniques. Purification yields are typically 70 to 80%. (Kelley, 2009). Anti-idiotypic zncRan / nznz / q / Yi antibodies Another aspect of the invention is directed to anti-idiotypic antibodies and anti-anti-idiotypic antibodies. An anti-idiotypic antibody is an antibody that recognizes the determinants of another antibody (a target antibody). Generally, the anti-idiotypic antibody recognizes the antigen-binding site determinants of the target antibody. Typically, the target antibody is a monoclonal antibody. An anti-idiotypic antibody is generally prepared by immunizing an animal (particularly, mice) of the same species and genetic type as the source of the target monoclonal antibody, with the target monoclonal antibody. The immunized animal mounts an immune response to the idiotypic determinants of the target monoclonal antibody and produces antibodies against the idiotypic determinants of the target monoclonal antibody. Antibody-producing cells, such as spleen cells, from the immunized animal can be used to generate anti-idiotypic monoclonal antibodies. In addition, an anti-idiotypic antibody can also be used to immunize animals to produce anti-anti-idiotypic antibodies. These immunized animals can be used to generate anti-anti-idiotypic monoclonal antibodies by standard techniques. Anti-idiotypic antibodies can bind to this epitope than the original target monoclonal antibody used to prepare the anti-idiotypic antibody. Anti-anti-idiotypic antibodies represent other monoclonal antibodies with the same antigen specificity as the original target monoclonal antibody. If the binding of the anti-idiotypic antibody to the target antibody is inhibited by the relevant antigen of the target antibody, and if the anti-idiotypic antibody elicits an antibody response with the same specificity as the target antibody, it mimics the antigen of the target antibody. . Such an anti-idiotypic antibody is an anti-idiotypic internal image and is capable of inducing an antibody response as if it were the original antigen. (Bona and Kohler, Anti-ldiotypic Antibodies And Infernal Image, in Monoclonal And Anti-ldiotypic Antibodies: Probes For Receptor Structure And Function, Venter J.C., Frasser, C.M., Lindstrom, J. (Eds.), Alan R. Liss, N.Y. , 1984. pp 141-149). Vaccines incorporating internal imaging anti-idiotypic antibodies have been shown to induce protective responses against viruses, bacteria, and parasites (Kennedy et., (1986) Science, 232:220-223; McNamara et. -1326). Internal imaging anti-idiotypic antibodies have also been shown to induce immunity to tumor-associated antigens (Raychauhuri et al. (1986) J. Immunol. 137:1743-1749; Raychauhuri et al. (1987) J. Immunol. 139 :3902-3910, Bhattacharya-Chatterjee et al (1987) J Immunol 139:1354-1360, Bhattacharya-Chatterjee et al (1988) J Immunol 141:1398-1403, Herlyn D et al. (1989) Intern Rev Immunol 4:347-357 Chen Z-J et al (1990) Cell Imm Immunother Cancer 351-359 Herlyn D et al (1991) In Vivo 5 :615-624, Furuya et al. (1992) Anticancer Res. 12:2732, Mittelman A. et al. (1992) Proc. Nati. Acad. Sel., USA 89:466-470, Durrant, L. G. et al. ( 1994) Cancer Res. et al (1995) J Immunother 18:95-103 Chakrobarty M et al (1995) Cancer Res 55:1525-1530 Foon KA et al (1995) Clin Cancer Res 1: 1205-1294;Herlyn, D, et al.(1995) Hybr language 14:159-166; Sclebusch, H. et al. (1995) Hybridoma 14:167-174; Herlyn, D. et al. (1996) Cancer Immunol Immunother. 43:65-76). Anti-idiotypic antibodies to MCT1 can be prepared, for example, by immunizing a zncRan / nznz / q / Yi animal, such as a mouse, with an immunogenic amount of a composition comprising MCT1 or immunogenic portions thereof, containing at least least one MCT1 antigenic epitope. The composition may also contain a suitable adjuvant and any carrier necessary to provide immunogenicity. Monoclonal antibodies that recognize MCT1 can be prepared from the cells of the immunized animal as described above. A monoclonal antibody that recognizes an epitope of MCT1 is then selected and used to prepare a composition comprising an immunogenic amount of the anti-MCT1 monoclonal antibody. Typically, a 25-200 pg dose of purified monoclonal MCT1 in a suitable adjuvant would suffice. Animals can be immunized 2-6 times at 14-30 day intervals between doses. Typically, animals are immunized by any suitable route of administration, such as intraperitoneal, subcutaneous, intravenous, or a combination of these. Anti-idiotypic antibody production can be monitored during the immunization period using standard immunoassay methods. Animals with adequate antibody titers reactive with the target monoclonal antibodies can be reimmunized with the monoclonal antibody used as immunogen three days prior to harvesting the antibody-producing cells. Preferably, spleen cells are used, although other antibody-producing cells may be selected. Antibody-producing cells are harvested and fused with myeloma cells to produce hybridomas, as described above, and suitable anti-idiotypic antibody-producing cells are selected. Anti-anti-idiotypic antibodies are produced by another round of immunization and hybridoma production using the anti-idiotypic monoclonal antibody as immunogen. Competition, epitope matching and structural similarity Identification of one or more antibodies that bind to substantially or essentially the same epitope as the monoclonal antibodies described herein can be readily determined by alanine scanning. In addition, any of a variety of immunological detection assays where antibody competition can be assessed. Several of these assays are commonly practiced and well known in the art (see, for example, US Patent No. 5,660,827, issued August 26, 1997, which is specifically incorporated herein by reference). It will be understood that, in fact, determining the epitope to which an antibody described herein binds is in no way necessary to identify an antibody that binds to the same or substantially the same or overlapping epitope as the monoclonal antibody described herein. For example, when the test antibodies to be examined are obtained from different animal sources, or even are of a different Ig isotype, a simple competition assay can be employed where the control antibody is mixed with the test antibody and it is then applied to a sample containing MCT1. Protocols that are based on ELISA, radioimmunoassays, Western blotting, and the use of the BIACORE® assay (GE Healthcare Life Sciences, Marlborough, MA) are suitable for use in such simple proficiency studies. In certain embodiments, the control anti-MCT1 antibody is premixed with zncRan / nznz / q / Yi varying amounts of the test antibody (eg, in ratios of about 1:1, 1:2, 1:10). or about 1:100) for a period of time before applying MCT1 antigen to the sample. In other embodiments, the control and varying amounts of test antibody can simply be added separately and mixed during exposure to the MCT1 antigen sample. Provided that bound antibodies can be distinguished from free antibodies (for example, by using separation or washing techniques to remove unbound antibodies) and control antibody from the test antibody (for example, by using antibodies species-specific or isotype-specific side effects or by specifically labeling the control antibody with a detectable label) it can be determined whether the test antibody reduces the binding of the control antibody to the MCT1 antigen, indicating that the test antibody substantially recognizes the MCT1 antigen. same epitope as the control anti-MCT1 antibody. Binding of the control (labeled) antibody in the presence of a completely irrelevant antibody (which does not bind to MCT1) can serve as the control high titer. The control low titer can be obtained by incubating the labeled control antibody with the same control antibody but not labeled, where competition would occur and reduce binding of the labeled antibody. In a test assay, a significant reduction in the reactivity of the labeled antibody in the presence of a test antibody is indicative of a test antibody that recognizes substantially the same epitope, ie, one that competes with the labeled control antibody. For example, any test antibody that reduces the binding of the control antibody to MCT1 by at least about 50%, such as at least about 60% or more, eg, at least about 70% (eg, about from 65-100%), at any test antibody ratio between about 1:1 or 1:10 and about 1:100 an antibody that substantially binds to this epitope or overlapping determinant is considered to be the test antibody. control. Preferably, said test antibody will reduce the binding of the control antibody to the MCT1 antigen, for example, at least about 50%, at least about 60%, at least about 80% or at least about 90% (for example , about 95%) of the binding of the control antibody observed in the absence of the test antibody. A simple competition assay in which a test antibody at a saturation concentration is applied to a surface onto which MCT1 (or a portion thereof) is immobilized may also be advantageously employed. The surface in the simple competition assay is, for example, a BIACORE® chip (GE Healthcare Life Sciences, Marlborough, MA) (or other suitable media for surface plasmon resonance (SPR) analysis). control antibody binding MCT1 to the MCT1-coated surface This binding to the MCT1-containing surface of the control antibody alone is compared to the binding of the control antibody in the presence of a test antibody A significant reduction in binding to surface area containing MCT1 by the control antibody in the presence of a test antibody indicates that the test antibody recognizes substantially the same epitope as the control antibody such that the test antibody competes with the control antibody.Any antibody of test that reduces control antibody binding by at least about 20% or more, at least about 40%, at least zncAan / nznz / q / Yi about 50% , at least about 70% or more, can be considered an antibody that binds to substantially the same epitope or determinant as the control antibody. Preferably, said test antibody will reduce the binding of the control antibody to MCT1 by at least about 50% (eg, at least about 60%, at least about 70% or more). It will be appreciated that the order of control and test antibodies can be reversed; that is, the control antibody may first bind to the surface and then the test antibody is contacted with the surface thereafter in a competition assay. Alternatively, the antibody that has the highest affinity for the MCT1 antigen binds first to the MCT1-containing surface, since the decrease in binding observed for the second antibody (assuming the antibodies compete) would be expected to be of greater magnitude. Additional examples of such assays are provided in, for example, Saunal and Regenmortel, J. Immunol. Methods, 183: 33-41 (1995), the disclosure of which is incorporated herein by reference. Furthermore, whether an antibody binds to the same or overlapping epitope on MCT1 as another antibody or to the epitope bound by a test antibody can be determined in particular using an assay that is based on Western blotting. In this assay, a peptide library corresponding to the antigen bound by the antibody, the MCT1 protein, is created comprising overlapping portions of the protein, typically 10-25, 10-20 or 10-15 amino acids long. These different overlapping amino acid peptides spanning the MCT1 sequence are synthesized and covalently attached to a PEPSPOTS™ nitrocellulose membrane (JPT Peptide Technologies, Berlin, Germany). Blots are prepared and probed according to manufacturer's recommendations. Essentially, the immunoblot assay then detects by fluorometric means which peptides in the library bind to the test antibody and can therefore identify which residues on the antigen, i.e. MCT1, interact with the test antibody. (See US Patent No. 7,935,340, incorporated herein by reference). Various epitope mapping techniques are known in the art. By way of example, X-ray co-crystallography of antigen and antibody; NMR; SPR (for example, at 25° or 37°C); matrix-based oligopeptide scanning (or pepscan analysis); site-directed mutagenesis (eg, alanine scanning); mutagenesis mapping; hydrogen-deuterium exchange; phage display; and limited proteolysis are all epitope mapping techniques that are well known in the art (see, for example, Epitope Mapping Protocols: Second Edition, Methods in Molecular Biology, eds. Mike Schutkowski and Ulrich Reineke, 2nd Ed., New York, NY: Humana Press (2009), and Epitope Mapping Protocols, Methods in Molecular Biology, Glenn Morris ed., 1st Ed., New York, NY: Humana Press (1996), both of which are incorporated herein by reference in their entireties). Identification of one or more antibodies that bind to substantially or essentially the same epitope as the monoclonal antibodies described herein, eg, MCT1 Ab1 or a variant thereof, can be readily determined by any of a variety of detection assays. immunology where antibody competition can be assessed. Several of these zncRan / nznz / q / Yi assays are commonly practiced and well known in the art (see, for example, US Patent No. 5,660,827, issued August 26, 1997, which is incorporated herein by reference). It will be understood that determining the epitope to which an antibody described herein binds is in no way necessary to identify an antibody that binds to the same or substantially the same epitope as the monoclonal antibody described herein. For example, when the test antibodies to be examined are obtained from different animal sources, or even are of a different Ig isotype, a simple competition assay can be employed where the control antibody (for example, MCT1 Ab1 or either Ab1-Ab95 or a fragment or variant of any of the above antibodies, for example) is mixed with the test antibody and then applied to a sample containing MCT1, known to be bound by MCT1 Ab1 and any of Ab1-Ab95. Protocols that are based on ELISA, radioimmunoassays, Western blotting, and BIACORE® analysis (GE Healthcare Life Sciences, Marlborough, MA) (as described in the Examples section herein) are suitable for use in such simple proficiency studies. . In certain embodiments, the method comprises premixing the control antibody with varying amounts of the test antibody (eg, in ratios of about 1:1, 1:2, 1:10, or about 1:100) for a period of time before applying to the sample MCT1 antigen. In other embodiments, the control and varying amounts of test antibody may be added separately and mixed during exposure to the MCT1 antigen sample. As long as the bound antibodies can be distinguished from free antibodies (for example, by using separation or washing techniques to remove unbound antibodies) and control antibody from the test antibody (for example, by using species-specific or isotype-specific secondary antibodies or by specifically labeling the control antibody with a detectable label), the method can be used to determine whether the test antibody reduces the binding of the control antibody to the MCT1 antigen, indicating that the control antibody test recognizes substantially the same epitope as the control antibody (eg, MCT1 Ab1 or any of Ab1-Ab95). Binding of the control (labeled) antibody in the presence of a completely irrelevant antibody (which does not bind to MCT1) can serve as the control high titer. The control low titer can be obtained by incubating the labeled control antibody with the same control antibody but not labeled, where competition would occur and reduce binding of the labeled antibody. In a test assay, a significant reduction in the reactivity of the labeled antibody in the presence of a test antibody is indicative of a test antibody that recognizes substantially the same epitope, ie, one that competes with the labeled control antibody. For example, any test antibody that reduces the binding of MCT1 Ab1 to MCT1 by at least about 50%, such as at least about 60% or more, eg, at least about 70% (eg, about 65 -100%), at any ratio of control MCT1 Ab1 test antibody between about 1:1 or 1:10 and about 1:100 is considered an antibody that substantially binds to this epitope or determinant than MCT1 Ab1 or any of Ab1-Ab95. zncRan / nznz / q / Yi Preferably, said test antibody will reduce the binding of MCT1 Ab1 to MCT1 to at least about 50%, at least about 60%, at least about 80%, or at least about 90% (for example, about 95% ) of MCT1 Ab1 binding observed in the absence of the test antibody. These methods can be adapted to identify and / or assess antibodies that compete with other control antibodies. A simple competition assay in which a test antibody at a saturation concentration is applied to a surface onto which MCT1 is immobilized can also be advantageously employed. The surface in the simple competition assay is, for example, a suitable medium for OCTET® and / or PROTEON®. The binding of a control antibody (eg, MCT1 Ab1 or any of Ab2-Ab95) to the MCT1-coated surface is measured. This binding to the MCT1-containing surface of the control antibody alone is compared to the binding of the control antibody in the presence of a test antibody. A significant reduction in binding to the MCT1-containing surface by the control antibody in the presence of a test antibody indicates that the test antibody recognizes substantially the same epitope as the control antibody such that the test antibody competes with the test antibody. control antibody. Any test antibody that reduces the binding of the control antibody (such as MCT1 Ab1) to MCT1 by at least about 20% or more, at least about 40%, at least about 50%, at least about 70% or more, an antibody can be considered that binds to substantially the same epitope or determinant as the control antibody (eg, MCT1 Ab1). Preferably, said test antibody will reduce the binding of the control antibody (eg MCT1 Ab1) to the MCT1 antigen by at least about 50% (eg at least about 60%, at least about 70% or more). . It will be appreciated that the order of control and test antibodies can be reversed; that is, the control antibody may first bind to the surface and then the test antibody is contacted with the surface thereafter in a competition assay. Preferably, the antibody that has higher affinity for MCT1 first binds to the MCT1-containing surface, since the decrease in binding observed for the second antibody (assuming the antibodies compete) would be expected to be of greater magnitude. Additional examples of such assays are provided in, for example, Saunal and Regenmortel, J. Immunol. Methods, 183: 33-41 (1989), the disclosure of which is incorporated herein by reference. The determination of whether an antibody, an antigen-binding fragment thereof, or an antibody derivative binds within one of the epitope regions defined above can be carried out in ways known to the mid-level artisan. In another example of such mapping / characterization methods, an epitope region for an anti-MCT1 antibody can be determined by the process of epitope footprinting through chemical modification of exposed amines / carboxyls in the MCT1 protein. A specific example of such a 'footprinting' technique is the use of hydrogen-deuterium exchange detected by mass spectrometry (HXMS), wherein hydrogen / deuterium exchange of protein ligand and receptor amide protons occurs, binding and exchange reverse, where the backbone amide groups that zncRan / nznz / q / Yi participate in protein binding are protected from reverse exchange and will therefore remain deuterated. Relevant regions can be identified at this point by peptic proteolysis, fast microhole high performance liquid chromatography separation, and / or electrospray ionization mass spectrometry (see, for example, Ehring H., Analytical Biochemistry, 267 ( 2): 252-259 (1999) and Engen, JR & Smith, DL, Anal. Chem., 73:256A-265A (2001)). Another example of a suitable epitope identification technique is nuclear magnetic resonance (NMR) epitope mapping, where typically the position of signals in two-dimensional NMR spectra of free antigen and antigen complexed with the binding peptide to antigen, such as an antibody, are compared. Typically, the antigen is selectively isotopically labeled with 15N such that only signals corresponding to the antigen are seen and no antigen-binding peptide signals are seen in the NMR spectrum. Antigen signals originating from amino acids involved in the interaction with the antigen-binding peptide will typically shift position in the complex spectra compared to the free antigen spectra, and the amino acids involved in binding can be identified differently. that way. See, for example, Ernst Schering Res. Found. Workshop, (44): 149-67 (2004); Huang et al., J. Mol. Bio!, 281(1):61-67 (1998); and Saito and Patterson, Methods, 9(3):516-24 (1996). Epitope mapping / characterization can also be performed via mass spectrometry (MS) methods (see, for example, Downard, J. Mass Spectrom., 35(4):493-503 (2000) and Kiselar and Downard , Ana!. Chem., 71(9): 1792-801 (1999)). Protease digestion techniques may also be useful in the context of epitope mapping and identification. Relevant regions / sequences of antigenic determinants can be determined by protease digestion, for example, using trypsin at a digestion ratio of about 1:50 to MCT1 overnight (o / n) at 37° C and pH 7-8, followed by mass spectrometry (MS) analysis for peptide identification. Peptides protected from trypsin cleavage by anti-MCT1 antibody can be further identified by comparing samples digested with trypsin and samples incubated with antibody and then digested, for example, with trypsin (thus thus reveals a fingerprint for the antibody). Other enzymes such as chymotrypsin or pepsin can be used in similar epitope characterization methods. In addition, enzymatic digestion can provide a rapid method of analyzing whether a potential antigenic determinant sequence is within a region of MCT1 in the context of an MCT1-binding polypeptide. If the polypeptide is not exposed to the surface, it is most likely not relevant in terms of immunogenicity / antigenicity (see, for example, Manca, Ann. 1st. Super. Sanita., 27 (1): 15-9 ( 1991) for a review of similar techniques). Site-directed mutagenesis is another useful technique for the characterization of a binding epitope. For example, in alanine scanning site-directed mutagenesis (also known as alanine scanning, alanine scanning mutagenesis, alanine scanning mutations, combinatorial alanine scanning, or alanine point mutation creation, for example), each residue within a protein segment is replaced with an alanine residue (or another residue such as valine zncRan / nznz / q / Yi where alanine is present in the wild-type sequence) through methodologies such as direct peptide synthesis or proteins, site-directed mutagenesis, the GENEART™ mutagenesis service (Thermo Fisher Scientific, Waltham, MA USA) or shotgun mutagenesis, for example. Thus, a series of single point mutants of the molecule are generated by this technique; the number of mutants generated is equivalent to the number of residues in the molecule, where each residue is replaced, one at a time, by a single alanine residue. Alanine is generally used to replace native (wild-type) residues because of its non-bulky, chemically inert methyl functional group that can mimic the secondary structure preferences that many other amino acids can have. Subsequently, the effects that replacing a native residue with an alanine has on the binding affinity to an alanine-scanning mutant and its binding partner can be measured through methods such as, but not limited to, SPR binding experiments. If a mutation leads to a significant reduction in binding affinity, the mutated residue is most likely involved in binding. Structural epitope-specific monoclonal antibodies (i.e., antibodies that do not bind to the unfolded protein) can be used as a positive control for binding affinity experiments to verify that alanine replacement does not influence the overall tertiary structure of the protein. (since changes to the overall fold of the protein may indirectly affect fixation and thus produce a false positive result). See, for example, Clackson and Wells, Science, 267: 383-386 (1995); Weiss et al., Proc. nati. Acad. Sci. USA, 97(16): 8950-8954 (2000); and Wells, Proc. nati. Acad. Sci. USA, 93: 1-6 (1996). Electron microscopy can also be used for epitope footprinting. For example, Wang et al., Nature, 355: 275-278 (1992) used the coordinated application of cryoelectron microscopy, three-dimensional image reconstruction, and X-ray crystallography to determine the physical fingerprint of a Fab fragment on the capsid surface of the native cowpea mosaic virus. Other forms of unlabeled assay for epitope assessment include SPR (commercially sold as the Bl ACORE® System, GE Healthcare Life Sciences, Marlborough, MA) and reflectometric interference spectroscopy (RifS) (See, for example, Fagerstam et al. Journal of Molecular Recognition, 3: 208-14 (1990), Nice et al., J. Chromatogr., 646: 159-168 (1993), Leipert et al., Angew. Chem. Int. Ed., 37:3308 -3311 (1998); Kroger et al., Biosensors and Bioelectronics, 17:937-944 (2002)). In some embodiments, an anti-MCT1 antibody of the invention may have the same or a similar structure as another anti-MCT1 antibody. In a preferred embodiment, an anti-MCT1 antibody of the invention has a structure similar to MCT1 Ab1 or any of Ab1Ab95. Structural similarity can be assessed by structural alignment of three-dimensional protein structures obtained by X-ray crystallography, NMR, or other known methods. A similar structure can be determined through an analysis of the difference in positions between the alpha C carbons in the CDRs of the two proteins being compared. Generally, an average RMSD of less than 5 Á, less than 4 Á, less than 3 Á, less than 2 Á, less than 1 Á, or zncRan / nznz / q / Yi less than 0.5 Á in one or more of the CDRs is indicative of a similar protein structure. Therefore, in one embodiment, an anti-MCT1 antibody of the invention has CDRs that adopt the same structure as those of MCT1 Ab1 with an average RMSD of less than 0.5 Á in a structural alignment. In another embodiment, an anti-MCT1 antibody of the invention may be similar to MCT1 Ab1 in protein surface physicochemical properties. In a particular embodiment, the antibody has the same surface charge as MCT1 Ab1 or that of either Ab1-Ab95 on the binding surface of the antibody. In another embodiment, it has the same electrostatic potential and / or hydrophobicity. Example Anti-MCT1 Antibodies, Antibody Fragments, and Fusion Proteins In one embodiment, an antibody of the invention comprises the heavy chain and light chain CDRs of MCT1 Ab1. In one embodiment, an antibody of the invention comprises the heavy chain CDRs of SEQ ID NO: 4, 5, 6 and the light chain CDRs of SEQ ID NO: 7, 8, 9. In one embodiment, an antibody or antibody fragment of the invention comprises the Vh domain and the Vl domain of MCT1 Ab1 or that of either Ab2-Ab95. In one embodiment, an antibody or antibody fragment of the invention comprises a Vh domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% identity to the amino acid sequence of SEQ ID NO: 2 or to any Vh domain of Ab2-Ab95. In one embodiment, an antibody or antibody fragment of the invention comprises a Vl domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% identity to the amino acid sequence of SEQ ID NO: 3 or to any Vl domain of Ab1-Ab95. In one embodiment, an antibody or antibody fragment of the invention comprises a Vh domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% identity to the amino acid sequence of SEQ ID NO: 2 and a Vl domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99 %, or 100% identity to the amino acid sequence of SEQ ID NO: 3. In one embodiment, an antibody or antibody fragment of the invention comprises a Vn domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity to the amino acid sequence of the Vh domain of any of Ab2Ab95 and an amino acid sequence of a VL domain that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98 %, at least 99%, or 100% identity to the amino acid sequence of the Ab1-Ab95 Vl domain, preferably where these homologous Vh and Vl domains correspond to those of the same antibody, ie, one of Ab2-Ab95. In one embodiment, a fusion protein of the invention comprises the heavy chain CDR3 of MCT1 Ab1 (SEQ ID NO: 6), or a variant thereof. In one embodiment, the fusion protein comprises a peptide that has at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity with the amino acid sequence of zncRan / nznz / q / Yi SEQ ID NO: 6. In particular, as the MCT1 Ab1 heavy chain CDR3 is longer than most CDRs and clearly extends beyond the plane of the antigen-binding surface on MCT1 Ab1, it is contemplated that a fusion protein comprising a peptide with this sequence (SEQ ID NO: 6), or a variant thereof, could retain one or more functions or binding capabilities of MCT1 Ab1. additional modifications Antibody conjugates In some embodiments, the present invention features antibody-drug conjugates (ADCs), which consist of an antibody (or antibody fragment such as a single-chain variable fragment (scFv)) linked to a payload (often cytotoxic) drug. antibody causes the ADC to bind to the target cancer cells.Often, the ADC is internalized by the cell and the drug is released into the cell.Due to targeting, side effects are less and give a wider therapeutic window. Hydrophilic linkers (eg, PEG4Mal) help prevent drug from being pumped out of resistant cancer cells via MDR (multi-drug resistance) transporters. In another aspect, the present invention features immunoconjugates comprising an anti-MCT1 antibody, or a fragment thereof, conjugated to a therapeutic agent, such as a cytotoxin, drug (eg, immunosuppressant), or radiotoxin. Such conjugates are referred to herein as immunoconjugates. Immunoconjugates that include one or more cytotoxins are called immunotoxins. A cytotoxin or cytotoxic agent includes any agent that is detrimental to (eg, kills) cells. Examples include taxol, cytochalasin B, gramicidin D, ethidium bromide, emetin, mitomycin, etoposide, teniposide, vincristine, vinblastine, colchicine, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol and puromycin and analogs or homologs thereof. Therapeutic agents also include, for example, antimetabolites (for example, methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarbazine), alkylating agents (for example, mechlorethamine, thiotepa chlorambucil, melphalan, carmustine (BSNU) and lumustine (CCNU), cyclophosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine platinum(II) (DDP) cisplatin), anthracyclines (for example, daunorubicin (formerly daunomycin) and doxorubicin), antibiotics (for example, dactinomycin, (formerly actinomycin) bleomycin, mithramycin, and anthramycin (AMC)) and antimitotic agents (eg, vincristine and vinblastine). Other examples of therapeutic cytotoxins that can be conjugated to an antibody in accordance with at least some embodiments of the invention include duocarmycins, calicheamicin, maytansins, and auristatins, and derivatives thereof. An example of a calicheamicin antibody conjugate is commercially available (Mylotarg™ Wyeth). Cytotoxins can be conjugated to antibodies in accordance with at least some embodiments of the invention using linker technology available in the art. Examples of zncRan / nznz / q / Yi types of linker that have been used to conjugate a cytotoxin to an antibody include, among others, hydrazones, thioethers, esters, disulfides, and peptide-containing linkers. A linker may be chosen that is, for example, susceptible to cleavage by low pH within the lysosomal compartment or susceptible to cleavage by proteases, such as proteases preferentially expressed in tumor tissue such as cathepsins (eg, cathepsins B, C, D). . For a more detailed discussion of types of cytotoxins, linkers, and methods for conjugating therapeutic agents to antibodies, see also Saito, G. et al. (2003) Adv. Drug Deliv. Rev 55: 199-215; Trail, PA and et al. (2003) Cancer Immunol. Immunother. 52:328-337; Payne, G. (2003) Cancer Cell 3:207-212; Alien, T. M. (2002) Nat. Rev. Cancer 2:750-763; Pastan, I. & Kreitman, R.J. (2002) Curr. Opinion. Investing. Drugs 3: 1089-1091; Senter, P.D. & Springer, C.J. (2001) Adv. Drug Deliv. Rev. 53: 247-264. The antibodies of the present invention can also be conjugated with a radioactive isotope to generate cytotoxic radiopharmaceuticals, also called radioimmunoconjugates. Examples of radioactive isotopes that can be conjugated to antibodies for diagnostic or therapeutic use include, but are not limited to, iodine 131, indium 111, ¡ttrium 90, and lutetium 177. Methods for preparing radioimmunoconjugates are established in the art. Radioimmunoconjugates are commercially available, including Zevalin® (BiogenIDEC) and Bexxar®. (Corixa Pharmaceuticals), and similar methods can be used to prepare radioimmunoconjugates using the antibodies according to at least some embodiments of the invention. The human anti-MCT1 antibodies and conjugates they contain according to at least some embodiments of the invention can be used to modify a given biological response, and the drug portion is not to be construed as limited to classical chemical therapeutic agents. For example, the drug portion can be a protein or polypeptide that possesses a desired biological activity. Such proteins may include, for example, an enzymatically active toxin, or an active fragment thereof, such as abrin, ricin A, pseudomonas exotoxin, or diphtheria toxin; a protein such as tumor necrosis factor or interferon-γ; or biological response modifiers such as lymphokines, interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL6), granulocyte-macrophage colony-stimulating factor (GM- CSF), granulocyte colony-stimulating factor (G-CSF), or other growth factors. Techniques for conjugating such a therapeutic moiety to antibodies are well known, see, for example, Arnon et al., Monoclonal Antibodies For Immunotargeting of Drugs in Cancer Therapy, in Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al., Antibodies For Drug Delivery, in Controlled Drug Delivery (2nd Ed.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker, Inc. 1987); Thorpe, Carriers Of Cytotoxic Agents In Cancer Therapy: A Review, in Monoclonal Antibodies '84: Biological And Clinical Applications, Finchera et al. (eds.), pp. 475-506 (1985); Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Antibody In Cancer Therapy, in Monoclonal Antibodies For Cancer Detection And Therapy, Baldwin et al. (eds.), pp. 303-16 (Academic Press 1985), and Thorpe et al., The Preparation And Cytotoxic Properties Of Antibody-Toxin Conjugates, Immunol. Rev 62: 119-58, 1982). zncRan / nznz / q / Yi Modifications to the constant regions, Fe domain and post-translational modifications In addition, or as an alternative to modifications made within the framework or CDR regions, antibodies according to at least some embodiments of the invention can be engineered to include modifications within the Fe region, generally to alter one or plus functional properties of the antibody, such as serum half-life, complement fixation, Fe receptor binding, and / or antigen-dependent cellular cytotoxicity. Furthermore, an antibody according to at least some embodiments of the invention may be chemically modified (for example, one or more chemical moieties may be attached to the antibody) or modified to alter its glycosylation, again to alter one or more functional properties of the antibody. . Said embodiments are further described below. The numbering of the residues in the Fe region is that of the Kabat EU index. In one embodiment, the CH1 hinge region is modified such that the number of cysteine ​​residues in the hinge region is altered, eg, increased or decreased. This approach is further described in US Patent No. 5,677,425 to Bodmer et al. The number of cysteine ​​residues in the CHI hinge region is altered to, for example, facilitate heavy and light chain assembly or to increase or decrease antibody stability. In another embodiment, the Fe hinge region of an antibody is mutated to decrease the biological half-life of the antibody. More specifically, one or more amino acid mutations are introduced into the CH2-CH3 domain interface region of the Fe hinge fragment such that the antibody has impaired staphylococcal protein A (SpA) binding relative to SpA binding. from the native Fe hinge domain. This approach is described in more detail in US Patent No. 6,165,745 to Ward et al. In another embodiment, the antibody is modified to increase its biological half-life. Several approaches are possible. For example, one or more of the following mutations can be introduced: T252L, T254S, and T256F, as described in US Pat. No. 6,277,375 to Ward. Alternatively, to increase biological half-life, the antibody can be altered within the CH1 or CL region to contain a rescue receptor-binding epitope taken from two loops of a CH2 domain of an IgG Fe region, as described in US Patent Nos. 5,869,046 and 6,121,022 to Presta et al. In still other embodiments, the Fe region is altered by replacing at least one amino acid residue with a different amino acid residue to alter the effector functions of the antibody. For example, one or more amino acids selected from amino acid residues 234, 235, 236, 237, 297, 318, 320, and 322 can be replaced with a different amino acid residue so that the antibody has altered affinity for an effector ligand but retains the antigen-binding capacity of the parent antibody. The effector ligand to which the affinity is altered may be, for example, an Fe receptor or the C1 component of complement. This approach is described in more detail in US Patent Nos. 5,624,821 and 5,648,260, both to Winter et al. In some embodiments, one or more amino acids selected from zncRan / nznz / q / Yi amino acid residues 329, 331, and 322 may be replaced with a different amino acid residue such that the antibody has impaired binding to C1q and / or has reduced or eliminated complement-dependent cytotoxicity (CDC). This approach is described in more detail in US Patent No. 6,194,551 to Idusogie et al. In another embodiment, one or more amino acid residues within amino acid positions 231 and 239 are altered to thereby alter the ability of the antibody to fix complement. This approach is further described in PCT publication WO 94 / 29351 to Bodmer et al. In yet another embodiment, the F region is modified to increase the affinity of the antibody for an Fy receptor by modifying one or more amino acids at the following positions: 238, 239, 248, 249, 252, 254, 255, 256 , 258 265, 267, 268, 269, 270, 272, 276, 278, 280, 283, 285, 286, 289, 290, 292, 293, 294, 295, 296, 298, 301,303, 305, 309, 307, 258 312, 315, 320, 322, 324, 326, 327, 329, 330, 331, 333, 334, 335, 337, 338, 340, 360, 373, 376, 378, 382, ​​388, 389, 398, 414, 416, 419, 430, 434, 435, 437, 438 or 439. This approach is further described in Presta PCT publication WO 00 / 42072. In addition, the binding sites on human IgG1 for FcyRI, FcyRIl, FcyRIII and FcRn have been mapped and variants with enhanced binding have been described (see Shields, RL et al. (2001^ J. Biol. Chem. 276: 6591-6604 Specific mutations at positions 256, 290, 298, 333, 334, and 339 have been shown to enhance FcyRIII binding.In addition, the following combined mutants are shown to enhance FcyRIII binding: T256A / S298A, S298A / E333A, S298A / K224A and S298A / E333A / K334A In addition, mutations such as M252Y / S254T / T256E or M428L / N434S enhance FcRn binding and increase the half-life of circulating antibodies (see Chan CA and Carter PJ (2010) Nature Rev Immunol 10: 301-316). In yet another embodiment, the antibody can be modified to abrogate Fab arm swapping in vivo. Specifically, this process involves the exchange of IgG4 semimolecules (one heavy chain plus one light chain) between other IgG4 antibodies effectively resulting in bispecific antibodies that are functionally monovalent. Mutations in the hinge region and heavy chain constant domains can abolish this exchange (see Aalberse, RC, Schuurman J., 2002, Immunology 105: 9-19). In yet another embodiment, glycosylation of the antibody is modified. For example, an aglycosylated antibody (ie, the antibody lacks glycosylation) can be prepared. Glycosylation can be altered to, for example, increase the affinity of the antibody for the antigen. Such carbohydrate modifications can be achieved, for example, by altering one or more glycosylation sites in the antibody sequence. For example, one or more amino acid substitutions that result in the removal of one or more glycosylation sites from the variable region can be made to thereby eliminate glycosylation at that site. Such aglycosylation can increase the affinity of the antibody for the antigen. Such an approach is described in more detail in US Patent Nos. 5,714,350 and 6,350,861 to Co et al. Additionally or alternatively, an antibody may be prepared that has an altered type of zncRan / nznz / q / Yi glycosylation, such as a hypofucosylated antibody that has reduced amounts of fucosyl residues or an antibody that has increased amounts of bisecting GIcNAc structures. . Such altered glycosylation patterns have been shown to increase the ADCC capacity of antibodies. Such carbohydrate modifications can be achieved, for example, by expressing the antibody in a host cell with altered glycosylation machinery. Cells with altered glycosylation machinery have been described in the art and these can be used as host cells in which recombinant antibodies are expressed according to at least some embodiments of the invention to thereby produce an antibody with a altered glycosylation. For example, the cell lines Ms704, Ms705, and Ms709 lack the fucosyltransferase gene, FUT8 (α(1,6)fucosyltransferase), so the antibodies expressed in the cell lines Ms704, Ms705, and Ms709 lack fucose in their carbohydrates. The Ms704, Ms705, and Ms709 FUT8 cell lines are created by targeted disruption of the FUT8 gene in CHO / DG44 cells using two replacement vectors (see US Patent Publication No. 20040110704 to Yamane et al. and Yamane-Ohnuki et al. (2004) Biotechnol Bioeng 87: 614-22). As another example, EP 1,176,195 to Hanai et al. describes a cell line with a functionally altered FUT8 gene, which encodes a fucosyl transferase, such that antibodies expressed in said cell line exhibit hypofucosylation by reducing or eliminating the 1,6-link-related enzyme. Hanai et al. also describes cell lines that have low enzymatic activity to add fucose to N-acetylglucosamine that binds to the Fe region of the antibody or that have no enzymatic activity, for example, the YB2 / 0 rat myeloma cell line (ATCC CRL 1662). Presta PCT publication WO 03 / 035835 describes a variant CHO cell line, Lecl3 cells, with reduced ability to bind fucose to Asn(297)-linked carbohydrates, which also results in hypofucosylation of antibodies expressed in that host cell (see also Shields, RL et al (2002) Blol. Chem. 2ΊΤ. 26733-26740). PCT Publication WO 99 / 54342 to Umana et al. describes cell lines engineered to express glycoprotein-modifying glycosyl transferases (eg, P(1,4)-N-acetllglucosamintransferase III (GnTIII)) such that antibodies expressed in the modified cell lines exhibit GIcNac structures increased bisectants resulting in increased ADCC activity of the antibodies (see also Umana et al. (1999) Nat. Biotech. 17: 176-180). Alternatively, the fucose residues of the antibody can be cleaved using a fucosidase enzyme. For example, fucosidase-L-fucosidase removes fucosyl residues from antibodies (Tarentino, A.L. et al. (1975) Biochem. 14: 5516-23). Another modification of the antibodies herein contemplated by the invention is pegylation or the addition of other water-soluble moieties, generally polymers, for example, to improve half-life. An antibody can be pegylated to, for example, increase the biological (eg, serum) half-life of the antibody. To pegylate an antibody, the antibody, or fragment thereof, is generally reacted with polyethylene glycol (PEG), as a reactive ester or aldehyde derivative of PEG, under conditions in which one or more PEG groups are attached to the antibody or fragment. of antibody. Preferably, the pegylation is carried out by means of an acylation reaction or an alkylation reaction with a reactive PEG molecule (or an analogous water-soluble reactive polymer). As zncRan / nznz / q / Yi is used herein, the term polyethylene glycol is intended to encompass any of the forms of PEG that have been used to derivatize other proteins, such as mono(Ci-Cio) alkoxy- or aryloxy polyethylene glycol or polyethylene glycol-maleimide . In certain embodiments, the antibody to be pegylated is an aglycosylated antibody. Methods for pegylating proteins are known in the art and can be applied to antibodies according to at least some embodiments of the invention. See, for example, EP 0 154 316 to Nishimura et al. and EP 0 401 384 to Ishikawa et al. nucleic acid molecules The invention further provides nucleic acids encoding an anti-MCT1 antibody according to the invention, or a fragment or conjugate thereof. The nucleic acids may be present in whole cells, in a cell lysate, or in a partially purified or substantially pure form. A nucleic acid is isolated or rendered substantially pure when other cellular components or contaminants, eg, other nucleic acids or cellular proteins, are removed during purification by conventional techniques, including alkaline / SDS treatment, CsCI banding, column chromatography , agarose gel electrophoresis and others well known in the art. See Ausubel, et al. (2011) Current Protocols in Molecular Biology, John Wiley & Sons, Inc. A nucleic acid according to at least some embodiments of the invention may be, for example, DNA or RNA and may or may not contain intronic sequences. In a preferred embodiment, the nucleic acid is a cDNA molecule. Nucleic acids according to at least some embodiments of the invention can be obtained using standard molecular biology techniques. In the case of antibodies expressed by hybridomas (for example, hybridomas prepared from transgenic mice bearing human immunoglobulin genes as described below), cDNAs encoding the light chain and heavy chain of the hybridoma-derived antibody can be obtained by standard PCR amplification techniques or cDNA cloning. In the case of antibodies obtained from an immunoglobulin library (eg, using phage display techniques), the nucleic acid encoding the antibody can be recovered from the library. Once the DNA fragments encoding the Vh and Vl segments have been obtained, these DNA fragments can be further manipulated by conventional recombinant DNA techniques, for example, to convert variable region genes into antibody chain length genes. complete, in Fab fragment genes or in an scFv gene. In these manipulations, the DNA fragment encoding Vl or Vh is operably linked to another DNA fragment encoding another protein, such as an antibody constant region or a flexible linker. As defined above, the term "operatively linked" means that the two DNA fragments are joined in such a way that the amino acid sequences encoded by the two DNA fragments remain in-frame. Isolated DNA encoding the Vh region can be converted into a full-length heavy chain gene by operatively ligating the Vh-encoding DNA to another DNA molecule encoding zncAan / nznz / q / Yi heavy chain constant regions ( CHI, CH2 and CH3). The sequences of human heavy chain constant region genes are known in the art (see, for example, Kabat, EA, et al. (1991) Sequences of Proteins of the Immunological Interest, Fifth Edition, U.S. Department of Health and US Human Services, NIH Publication No. 91-3242), and DNA fragments spanning these regions can be obtained by standard PCR amplification. The heavy chain constant region may be an IgG1, IgG2, IgG3, IgG4, IgA, IgE, IgM or IgD constant region, but most are, for example, an IgGI, IgG2 or IgG4 constant region. For a Fab fragment heavy chain gene, the DNA encoding VH can be operatively linked to another DNA molecule encoding only the heavy chain CH1 constant region. Isolated DNA encoding the Vl region can be converted into a full-length light chain gene (as well as a Fab light chain gene) by operatively ligating the Vl-encoding DNA to another DNA molecule encoding the Vl constant region. light chain, CL- Human light chain constant region gene sequences are known in the art (see, for example, Kabat, E. A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, US Department of Health and Human Services, NIH Publication No. 91-3242) and DNA fragments spanning these regions can be obtained by standard PCR amplification. The light chain constant region can be a kappa (k) or lambda (λ) constant region, but most, for example, are a k constant region. To create an scFv gene, the DNA fragments encoding Vh and Vl are operatively ligated to another fragment encoding a flexible linker, for example, encoding the amino acid sequence (Gly4-Ser)3, such that the Vh and Vh sequences Vl can be expressed as a contiguous single-chain protein, with the Vl and Vh regions joined by the flexible linker (see, for example, Bird et al. (1988) Science 242: 423-426; Huston et al. (1988) Proc. Nati. Acad. Sel., USA 85: 5879-5883; McCafferty et al., (1990) Nature 348: 552-554). Vectors The present invention also provides vectors into which a DNA of the present invention is inserted. Retrovirus-derived vectors are suitable tools to achieve long-term gene transfer, as they allow for genetic stability and high expression, as well as having a flexible genome. Furthermore, clinical experience with retroviral vectors provides guidance to optimize the efficacy and safety of their use. In summary, expression of natural or synthetic nucleic acids encoding antibodies or antigen-binding fragments thereof is typically achieved by operatively linking a nucleic acid encoding the antibody or antigen-binding fragment thereof, or portions thereof, to a promoter, and incorporating the construct into an expression vector. The vectors may be suitable for replication and integration in eukaryotes. Typical cloning vectors contain transcription and translation terminators, initiation sequences, and promoters useful for regulation of expression of the desired nucleic acid sequence. zncAan / nznz / q / Yi Nucleic acid can be cloned into various types of vectors. For example, the nucleic acid can be cloned into a vector including, but not limited to, a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid. Vectors of particular interest include expression vectors, replication vectors, probe generation vectors, and sequencing vectors. Furthermore, the expression vector can be provided to a cell in the form of a viral vector. Viral vector technology is well known in the art and is described, for example, in Sambrook et al. (2001, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York), and in other textbooks of virology and molecular biology. Viruses, which are useful as vectors include, among others, retroviruses, gamma retroviruses, adenoviruses, adeno-associated viruses, herpes viruses, and lentiviruses. In general, a suitable vector contains an origin of replication functional in at least one organism, a promoter sequence, convenient restriction endonuclease sites, and one or more selectable markers (for example, WO 01 / 96584; WO 01 / 29058; and WO 01 / 29058; U.S. Patent No. 6,326,193). Various virus-based systems have been developed for gene transfer into mammalian cells. For example, retroviruses provide a convenient platform for gene delivery systems. A selected gene can be inserted into a vector and packaged into retroviral particles using techniques known in the art. The recombinant virus can be isolated and administered to the cells of the subject in vivo or ex vivo. Various retroviral systems are known in the art. In some embodiments, adenovirus vectors are used. Various adenovirus vectors are known in the art. In one embodiment, retrovirus vectors are used. Additional promoter elements, eg enhancers, regulate the frequency of transcriptional initiation. These are normally found in the region 30-110 bp upstream of the start site, although several promoters have recently been shown to contain functional elements downstream of the start site as well. The spacing between promoter elements is often flexible so that promoter function is preserved when the elements are inverted or moved relative to each other. In the thymidine kinase (tk) promoter, the spacing between promoter elements can be increased to 50 bp apart before activity begins to decline. Depending on the promoter, it appears that individual elements may work cooperatively or independently to activate transcription. Various promoter sequences may be used, including, but not limited to, the cytomegalovirus (CMV) immediate early promoter, the elongation growth factor-ία (EF-1a), the simian virus 40 (SV40) early promoter, the virus mouse mammary tumor tumor (MMTV), the human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, the MoMuLV promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter , a Rous sarcoma virus promoter, as well as promoters from human genes such as, inter alia, the actin promoter, the myosin promoter, the hemoglobin promoter, and the creatine kinase promoter. Furthermore, the invention should not be limited to the use of constitutive promoters. Inducible promoters are also contemplated as part of the invention. The use of an inducidle zncRan / nznz / q / Yi promoter provides a molecular switch capable of turning on expression of the polynucleotide sequence that is operably linked when such expression is desired, or turning off expression when expression is not desired. Examples of inducible promoters include, but are not limited to, a metallothionein promoter, a glucocorticoid promoter, a progesterone promoter, and a tetracycline promoter. To assess the expression of an antibody, an antigen-binding fragment of an antibody, or a portion thereof, the expression vector to be introduced into a cell may also contain a selectable marker gene or a marker gene or both to facilitate identification. and selection of expression cells from the population of cells to be transfected or infected via viral vectors. In other aspects, the selectable marker can be carried on a separate DNA fragment and used in a cotransfection procedure. Both selectable markers and reporter genes can be flanked by appropriate regulatory sequences to allow expression in host cells. Useful selectable markers include, for example, antidiotic resistance genes, such as neo and the like. Reporter genes are used to identify potentially transfected cells and to assess the functionality of regulatory sequences. In general, a reporter gene is a gene that is not present or expressed by the recipient organism or tissue and that encodes a polypeptide whose expression is manifested by some readily detectable property, eg, enzymatic activity. Expression of the reporter gene is analyzed at a suitable time after the DNA has been introduced into the recipient cells. Suitable reporter genes may include genes encoding luciferase, beta-galactosidase, chloramphenicol acetyl transferase, secreted alkaline phosphatase, or the green fluorescent protein gene (eg, Ui-Tei et al., 2000 FEBS Letters 479: 79-82). . Suitable expression systems are well known and can be prepared using known techniques or obtained commercially. In general, the construct with the minimal 5' flanking region showing the highest level of reporter gene expression is identified as the promoter. Such promoter regions can be linked to a reporter gene and used to test agents for the ability to modulate promoter-directed transcription. transduction Methods for introducing and expressing genes into a cell are known in the art. In the context of an expression vector, the vector can be readily introduced into a host cell, eg, mammalian, bacterial, yeast, or insect cells by any method in the art. For example, the expression vector can be transferred to a host cell by physical, chemical, or biological means. Physical methods for introducing a polynucleotide into a host cell include calcium phosphate precipitation, lipofection, particle bombardment, microinjection, electroporation, and the like. Methods for producing cells comprising vectors and / or exogenous nucleic acids are well known in the art. See, for example, Sambrook et al. (2001, Molecular Cloning: A Laboratory zncAan / nznz / q / Yi Manual, Cold Spring Harbor Laboratory, New York). A preferred method for introducing a polynucleotide into a host cell is calcium phosphate transfection. Biological methods for introducing a polynucleotide of interest into a host cell include the use of DNA and RNA vectors. Viral vectors, and especially retroviral vectors, have become the most widely used method of inserting genes into mammalian, eg, human cells. Other viral vectors can be derived from lentiviruses, poxviruses, herpes simplex virus I, adenoviruses and adeno-associated viruses, and the like. See, for example, US Patent Nos. 5,350,674 and 5,585,362. Chemical means for introducing a polynucleotide into a host cell include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. An exemplary colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (eg, an artificial membrane vesicle). In the case where a non-viral delivery system is used, an exemplary delivery vehicle is a liposome. The use of lipid formulations for the introduction of the nucleic acids into a host cell (in vitro, ex vivo or in vivo) is contemplated. In another aspect, the nucleic acid may be associated with a lipid. Lipid-associated nucleic acid can be encapsulated within the aqueous interior of a liposome, embedded within the lipid bilayer of a liposome, attached to a liposome through a linker molecule that is associated with the liposome and the oligonucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a lipid-containing solution, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained in or complexed with a micelle, or associated with a lipid. Compositions associated with lipids, lipids / DNA or lipids / expression vectors are not limited to any particular structure in solution. For example, they may be present in a bilayer structure, such as micelles, or with a folded structure. They can also simply be intercalated in a solution, possibly forming aggregates that are not uniform in size or shape. Lipids are fatty substances that can be natural or synthetic lipids. For example, lipids include the naturally occurring fat droplets in the cytoplasm, as well as the class of compounds that contain long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, amino alcohols, and aldehydes. Suitable lipids for use can be obtained from commercial sources. For example, dimyristyl phosphatidylcholine (DMPC) can be obtained from Sigma, St. Louis, Mo.; dicetyl phosphate (DCP) is available from K & K Laboratories (Plainview, NY); cholesterol (Choi) can be obtained from Calbiochem-Behring; dimyristyl phosphatidylglycerol (DMPG) and other lipids are available from Avanti Polar Lipids, Inc. (Birmingham, Ala.). Stock solutions of lipids in chloroform or chloroform / methanol can be stored at around -20 degrees Celsius. Chloroform is used as the only solvent since it evaporates more easily than methanol. Liposome is a generic term that encompasses a variety of simple and multilamellar lipid vehicles formed by the generation of closed lipid bilayers or aggregates. Liposomes can be characterized as having zncAan / nznz / q / Yi vesicular structures with a phospholipid bilayer membrane and an internal aqueous medium. Multilamellar liposomes have multiple lipid layers separated by aqueous media. They form spontaneously when phospholipids are suspended in an excess of aqueous solution. The lipid components undergo rearrangement prior to the formation of closed structures and trap water and dissolved solutes between lipid bilayers (Ghosh et al., 1991 Glycobiology 5:505-10). However, compositions having different solution structures than the normal vesicular structure are also included. For example, lipids can assume a micellar structure or simply exist as non-uniform aggregates of lipid molecules. Lipofectamine-nucleic acid complexes are also contemplated. Regardless of the method used to introduce foreign nucleic acids into a host cell or expose a cell to the inhibitor of the present invention, a variety of assays can be performed to confirm the presence of the recombinant DNA sequence in the host cell. Such assays include, for example, molecular biological assays well known to the mid-level trade, such as Southern and Northern blotting, RT-PCR and POR; biochemical assays, such as detecting the presence or absence of a particular peptide, for example, by immunological means (ELISA and Western blots) or by assays described herein to identify agents that fall within the scope of the invention. therapeutic applications The isolated anti-MCT1 antibodies or antigen-binding fragments thereof obtained by the above methods, or compositions containing them, can be used as a medicament in the treatment of a disease, disorder or condition in a subject. In some embodiments, said medicament can be used to treat an autoimmune, inflammatory, or allergic condition. In some embodiments, the medicament can be used for the treatment of cancer. In some embodiments, the medicament can be used for the treatment of EIHI. Subject The subject referred to herein can be any living subject. In a preferred embodiment, the subject is a mammal. The mammal referred to herein can be any mammal. As used herein, the term "mammal" refers to any mammal, including, but not limited to, mammals of the order Rodentia, such as mice and hamsters, and mammals of the order Logomorpha, such as rabbits. Mammals can be of the order Carnivora, which includes felines (cats) and canines (dogs). Mammals may be of the Artiodactyl order, including Bovine (cows) and Porcine (pigs) or Perssodactyl order, including Equine (horses). Mammals can be of the order Primates, Ceboides or Simoides (monkeys) or of the order Anthropoides (humans and apes). In some embodiments, the subject to which the antibodies, antibody fragments, or compositions are administered is a primate, such as a human. In some embodiments, the zncRan / nznz / q / Yi primate is a monkey or ape. The subject may be male or female and may be of any suitable age, including infants, youth, adolescents, adults, and the elderly. In some examples, the patient or subject is a validated animal model for disease, antibody therapy, and / or for evaluating toxic outcomes. In some embodiments, the subject has persistent or recurrent disease, eg, after treatment with other immunotherapy and / or other therapy, including chemotherapy, radiation, and / or hematopoietic stem cell transplantation (HSCT), eg, allogeneic HSCT. In some embodiments, the administration effectively treats the subject despite the fact that the subject has become resistant to another therapy. In some embodiments, the subject has not relapsed, but is determined to be at risk of relapse, such as a high risk of relapse, and therefore the compound or composition is administered prophylactically, for example, to reduce the likelihood or prevent relapse. In some embodiments, the methods include administration of anti-MCT1 antibodies, antibody fragments, or compositions containing the same to a subject, tissue, or cell. The subject to be treated, or from whom the tissue or cell is derived, may be one who has, is at risk of, or is suspected of having a disease, condition, or disorder associated with the expression of MCT1. In some embodiments, the antibodies, antibody fragments, or compositions are administered to a subject having the particular disease or condition to be treated. In some embodiments, the antibodies, antibody fragments, or compositions are administered to a subject, such as a subject who has or is at risk of the disease or condition. In some aspects, the methods thereby address, for example, ameliorating one or more symptoms of the disease or condition, such as decreasing the proportion of activated T-lymphocytes or B-lymphocytes that mediate an autoimmune disorder. Functional activity and / or evaluation MCT1 inhibition can be used to reduce autoimmune responses. Down-regulation may be in the form of inhibiting or blocking an autoimmune response that is already in progress, or it may involve preventing the induction of an autoimmune response. Activated immune cell functions can be inhibited by MCT1-mediated inhibition of lactate transport. For example, MCT1 Ab1 can bind to MCT1, which is expressed and immunologically relevant on activated T cells and B cells, thereby modulating the autoimmune response mediated by these cells. As described herein, other anti-MCT1 antibodies can be identified by, for example, their ability to inhibit activated T-lymphocyte activity or proliferation and / or based on their immunosuppressive effects in vitro or in models of inflammatory, allergic, or autoimmune disease. . Various readouts recognized in the cell activation technique can be used to measure, for example, cell proliferation or effector function (eg, antibody production, cytokine production, phagocytosis) in the presence of the anti-MCT1 antibody or binding fragment. to its antigen. The ability of a test antibody to inhibit MCT1 can be easily determined zncAon / nznz / q / Yl· by measuring the ability of the antibody to effect a decrease in proliferation or effector function being measured. Therefore, the ability of a test antibody to be immunosuppressive and to block autoimmune activation can be determined by measuring cytokine production and / or proliferation at different concentrations of antigen. In some embodiments, the production or secretion of inflammatory cytokines can be used to monitor the efficacy of the methods of treatment of the invention. In some embodiments, the efficacy of treatment with the antibodies of the invention can be measured by detection of ketones in urine. In particular, since MCT1 Ab1 does not cross-react with rodent MCT1, in vivo results in mouse studies may suggest that ketonuria could be directly induced from human leukocytes, since these are the only target cells in mice. NSG. Furthermore, some of the observed immunomodulatory effects of MCT1 inhibition may result indirectly from ketone generation, as studies have shown that increased blood ketone levels can suppress the inflammasome (REF. 67). In some aspects, the efficacy of treatment with the antibodies of the invention is measured by evaluating clinical outcome. For the treatment of autoimmune, inflammatory or allergic conditions, the efficacy of the treatment can be measured by the improvement of the condition. For example, decreased lupus symptoms, better survival in GVHD, reduced graft rejection, decreased concentration of autoantibodies, etc. In the case of cancer treatment, this could include reduction of tumor burden, tumor stabilization, progression-free survival, or overall survival. In the case of the treatment of EIHI, this clinical result can include the reduction of hypoglycemia after physical activity. Down regulation of immune responses MCT1 inhibition can be used to reduce immune responses. Down-regulation may be in the form of inhibiting or blocking an immune response that is already in progress, or may involve preventing the induction of an immune response. Activated immune cell functions can be inhibited by reducing immune cell responses or by inducing specific anergy in the immune cells, or both. For example, anti-MCT1 antibodies can bind to MCT1 on activated T cells and thus modulate the immune response. This antibody can be monospecific or multispecific, for example it can comprise a bispecific antibody such as a BiTE. For example, said antibody may comprise an MCT1 antigen-binding portion and another antigen-binding portion, eg, that is directed to a cell surface receptor on an immune cell, eg, an activated T cell or B cell. . Said antibody, in addition to comprising a binding site to the MCT1 antigen, may comprise a binding site that binds to a B lymphocyte antigen receptor, a T lymphocyte antigen receptor or an Fe receptor or another, to direct the molecule to a specific cell population. Selection of this second antigen for the bispecific antibody provides flexibility in zncRon / nznz / q / Yl· selection of the target cell population. As described herein, other human MCT1-binding antibodies can be identified by their ability to inhibit T-lymphocyte or B-lymphocyte activity or proliferation and / or based on their immunosuppressive effects in vitro or in inflammatory, allergic disease models. or autoimmune. Tolerance against specific antigens can be induced by co-administration of an antigen with an anti-MCT1 antibody according to the invention. For example, tolerance to specific polypeptides can be induced. Immune responses to allergens or to foreign polypeptides to which an immune response is not desired can be inhibited. For example, patients receiving Factor VIII frequently develop antibodies against this coagulation factor. Co-administration of an anti-MCT1 antibody according to the invention with recombinant factor VIII can suppress this unwanted immune response. An anti-MCT1 antibody according to the invention may be used in combination with another agent that blocks the activity of costimulatory receptors on an immune cell or agonizes the activity of an immunosuppressive receptor or ligand expressed on immune cells to modulate responses. immune Example molecules include: PD-1, PDL-1 agonists, soluble forms of CTLA-4, anti-B7-1 antibodies, anti-B7-2 antibodies, antagonist antibodies directed at one or more of LAG-3, TIM -3, BTLA, B7-H4, B7H3, et al. and / or agonist antibodies directed to one or more of CD40, CD137, 0X40, GITR, CD27, CD28, ICOS, or VISTA or combinations thereof. These portions may be combined in a single composition or compound, for example, a bispecific antibody containing an anti-MCT1 antibody according to the invention and further comprising an immune agonist antibody or may comprise a fusion polypeptide containing an anti-MCT1 antibody. MCT1 according to the invention that is fused with another immunosuppressive polypeptide or another active agent. Alternatively, these portions can be administered as separate or discrete entities (simultaneously or sequentially) in the same or different compositions to reduce immune cell-mediated immune responses in a subject. Examples of specific immunoinhibitory molecules that can be combined with anti-MCT1 antibodies according to the invention include antibodies that block a costimulatory signal (for example, against CD28 or ICOS), antibodies that activate an inhibitory signal through CTLA4, and / or o Antibodies against other immune cell markers (for example, against CD40, CD40 ligand, or cytokines), fusion proteins (for example, CTLA4-Fc or PD-I-Fc), and immunosuppressive drugs (for example, rapamycin, cyclosporine A, or FK506 ). In a further embodiment, the bispecific antibodies containing anti-MCT1 antibodies according to the invention are useful for targeting a specific cell population, eg using a marker found only on a certain cell type, eg , activated T lymphocytes or B lymphocytes. Reduction of immune responses by blockade of MCT1 is useful for modulating the immune response, for example, in tissue, skin, and organ transplant situations, in graft-versus-host-disease (GVHD) or allergies, or in autoimmune diseases and inflammatory diseases such as systemic lupus erythematosus, IBD, RA, psoriasis, and zncRan / nznz / q / Yi multiple sclerosis. For example, blocking MCT1 function results in reduced tissue destruction in tissue transplantation. Generally, in tissue transplants, rejection of the transplant is initiated through its recognition as foreign by immune cells, followed by an immune reaction that destroys the transplant. Administration of a molecule that inhibits MCT1 in immune cells alone or in combination with another depleting agent prior to or at the time of transplantation may inhibit the generation of a costimulatory signal. In addition, MCT1 blockade may also be sufficient to energize immune cells, thereby inducing tolerance in a subject. To achieve sufficient immunosuppression or tolerance in some diseases or in some subjects, it may be necessary to block the costimulatory function of other molecules. For example, it may be desirable to block the function of B7-1 and B7-2 by administering in a soluble form a combination of peptides that have activity from each of these antigens or by blocking antibodies against these antigens (eg. separately or together in a single composition) before or at the time of transplantation. Alternatively, it may be desirable to block MCT1 and further inhibit a costimulatory activity of B7-1 and / or B7-2. The subject's anti-MCT1 antibodies are especially useful in the treatment of autoimmune diseases. Many autoimmune disorders are the result of inappropriate activation of immune cells that are reactive against auto tissue and that promote the production of cytokines and autoantibodies involved in disease pathology. Preventing the activation of autoreactive immune cells can reduce or eliminate the symptoms of the disease. Administration of anti-MCT1 antibodies to the subject may induce antigen-specific tolerance of autoreactive immune cells, which could lead to long-term alleviation of disease. In addition, co-administration of agents that block immune cell costimulation by altering receptor-ligand interactions of B7 molecules with costimulatory receptors may be useful in inhibiting immune cell activation to prevent autoantibody or cytokine production that can be involved in the disease process. Down-regulation of an immune response through the subject's anti-MCT1 antibodies may also be useful in the treatment of autoimmune attack of autologous tissues. Therefore, conditions caused or exacerbated by autoimmune attack (eg, heart disease, myocardial infarction, or atherosclerosis) can be mitigated or ameliorated by MCT1 inhibition. Therefore, it is within the scope of the invention to modulate conditions exacerbated by autoimmune attack, such as autoimmune disorders (as well as conditions such as heart disease, myocardial infarction, and atherosclerosis) by inhibiting MCT1 using the anti-MCT1 antibodies. humans. As mentioned above, the efficiency of anti-MCT1 antibodies according to the invention in preventing or alleviating autoimmune and inflammatory disorders can be determined by using various well-characterized animal models of autoimmune diseases e zncRan / nznz / q / Yi human inflammatory Examples include murine experimental autoimmune encephalitis, systemic lupus erythematosus in MRL / lpr / lpr mice or NZB hybrid mice, murine autoimmune collagen arthritis, diabetes mellitus in NOD mice and BB rats, and murine experimental myasthenia gravis. See Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pages 840-856. Inhibition of immune cell activation is further useful therapeutically in the treatment of allergies and allergic reactions, for example, by inhibiting IgE production. The subject's anti-MCT1 antibodies can be administered to an allergic subject to inhibit immune cell-mediated allergic responses in the subject. MCT1 inhibition can be accompanied by exposure to the allergen together with appropriate MHC molecules. Allergic reactions can be systemic or local in nature, depending on the route of entry of the allergen and the pattern of IgE deposition on mast cells or basophils. Therefore, immune cell-mediated allergic responses can be locally or systemically inhibited by administration of the human anti-MCT1 antibodies. Treatment of autoimmune, inflammatory or allergic conditions. Antibodies, antibody fragments and pharmaceutical compositions according to the invention can be used to inhibit activated T-lymphocytes or B-lymphocytes and to treat conditions where this is therapeutically desirable, such as autoimmunity, allergy or inflammatory conditions. These compositions will comprise an amount of an antibody or antibody fragment according to the invention effective to suppress B cell activity or T cell activation or proliferation or cytokine expression in a subject in need thereof. Such autoimmune, inflammatory, and allergic conditions include, for example, arthritic conditions such as rheumatoid arthritis (RA), psoriatic arthritis, psoriasis, scleroderma, multiple sclerosis, lupus, IBD, ITP, diabetes, GvHD, sarcoidosis, allergic asthma, and hepatotoxicity associated with hepatitis. These antibodies can also be used to inhibit unwanted T cell immune responses against transplanted cells, tissues or organs, such as tissue grafts, CAR-T cells or cell-containing gene therapy constructs and the like. Specific conditions where the antibodies of the invention can be used alone or in association with other treatments, especially other immunosuppressive molecules include acquired immunodeficiency syndrome (AIDS), acquired splenic atrophy, acute anterior uveitis, acute disseminated encephalomyelitis (ADEM), acute gouty arthritis , acute necrotizing hemorrhagic leukoencephalitis, acute or chronic sinusitis, acute purulent meningitis (or other inflammatory disorders of the central nervous system), acute severe inflammation, Addison's disease, adrenalitis, adult-onset diabetes mellitus (type II diabetes), idiopathic hypoparathyroidism of adult onset (AOIH), agammaglobulinemia, agranulocytosis, vasculitis, including vasculitis, optionally, large vessel vasculitis, optionally, polymyalgia rheumatica and giant cell arthritis (Takayasu), allergic conditions, allergic contact dermatitis, allergic dermatitis, allergic angiitis granulomatous, allergic hypersensitivity disorders, allergic neuritis, allergic reaction, alopecia areata, alopecia totalis, Alport's zncRan / nznz / q / Yi syndrome, alveolitis, optional allergic alveolitis or fibrosing alveolitis, Alzheimer's disease, amyloidosis, ALS ; Lou Gehrig's disease), an eosinophil-related disorder, optionally eosinophilia, anaphylaxis, ankylosing spondylitis, angiectasis, antibody-mediated nephritis, anti-GBM / Anti-TBM nephritis, antigen-antibody complex-mediated diseases, antiglomerular basement membrane disease , antiphospholipid antibody syndrome, antiphospholipid syndrome (APS), thrush, aphthous stomatitis, aplastic anemia, arrhythmia, arteriosclerosis, arteriosclerotic disorders, arthritis, optionally rheumatoid arthritis, such as acute arthritis or chronic rheumatoid arthritis, progressive chronic arthritis, arthritis deformans, ascariasis, Aspergilloma, eosinophil-containing granulomas, aspergillosis, aspermiogenic, asthma, optionally bronchial asthma, bronchial asthma or autoimmune asthma, ataxia telangiectasia, nontoxic sclerosis, atherosclerosis, autism, autoimmune angioedema, autoimmune aplastic anemia, autoimmune atrophic gastritis, autoimmune diabetes itaria, autoimmune disease of the testis and ovary including orchitis and oophoritis, autoimmune disorders associated with collagen disease, autoimmune dysautonomia, autoimmune ear disease, optionally autoimmune inner ear disease (AGED), autoimmune endocrine diseases, including thyroiditis such as autoimmune thyroiditis, autoimmune enteropathy syndrome, autoimmune gonadal failure, autoimmune hearing loss, autoimmune hemolysis, autoimmune hepatitis, autoimmune liver disorder, autoimmune hyperlipidemia, autoimmune immunodeficiency, autoimmune inner ear disease (AIED), autoimmune myocarditis, autoimmune neutropenia, autoimmune pancreatitis, autoimmune polyendocrinopathies, autoimmune polyglandular syndrome type I, autoimmune retinopathy, autoimmune thrombocytopenic purpura (ATP), autoimmune thyroid disease a, autoimmune urticaria, autoimmune gastrointestinal diseases, neuronal and axonal neuropathies, Balo's disease, Behcet's disease, benign familial lesion and ischemia-reperfusion, benign lymphocytic angiitis, Berger's disease (IgA nephropathy), poultry farmers' lung disease, blindness, Boeck's disease, bronchiolitis obliterans (without transplantation) vs NSIP, bronchitis, bronchopneumonic aspergillosis, Bruton's syndrome, bullous pemphigoid, Caplan's syndrome, cardiomyopathy, cardiovascular ischemia, Castleman's syndrome, celiac disease, celiac disease Sprue (gluten enteropathy), cerebral degeneration, cerebral ischemia and vascularization accompanying the disease, Chagas disease, channelopathies, optionally epilepsy, CNS channelopathies, chorioretinitis, choroiditis, an autoimmune haematological disorder, chronic active hepatitis or autoimmune chronic active hepatitis, chronic contact dermatitis, pneumonia chronic eosinophilic chronic fatigue syndrome, chronic hepatitis, chronic hypersensitivity pneumonitis, chronic inflammatory arthritis, chronic inflammatory demyelinating polyneuropathy (CIDP),chronic intractable inflammation, chronic mucocutaneous candidiasis, chronic neuropathy, optionally IgM polyneuropathies or IgM-mediated neuropathy, chronic obstructive airway disease, chronic inflammatory lung disease, chronic relapsing multifocal osteomyelitis (CRMO), chronic thyroiditis (Hashimoto's thyroiditis) or thyroiditis subacute, Churg-Strauss syndrome, cicatricial pemphigoid / benign mucosal pemphigoid, inflammatory disorders of the CNS, CNS vasculitis, celiac disease, Cogan's syndrome, zncRan / nznz / q / Yi cold agglutinin disease, polypous colitis, colitis as ulcerative colitis, collagenous colitis, conditions involving T-lymphocyte infiltration and chronic inflammatory responses, congenital heart block, congenital rubella infection, Coombs-positive anemia, coronary artery disease, Coxsackie myocarditis, CREST syndrome (calcinosis, Raynaud's), Crohn's disease, cryoglobulinemia, syndrome Cushing's, cyclitis, optionally chronic cyclitis, heterochronic cyclitis, iridocyclitis or Fuch's cyclitis, cystic fibrosis, cytokine-induced toxicity, deafness, degenerative arthritis, demyelinating diseases, optionally autoimmune demyelinating diseases, demyelinating neuropathies, dengue fever, dermatitis herpetiformis and atopic dermatitis, dermatitis including contact dermatitis, dermatomyositis, dermatoses with acute inflammatory components, Devic's disease (neuromyelitis optica), diabetic disorder of the great arteries, diabetic nephropathy, diabetic retinopathy, Diamond Blackfan anemia, diffuse interstitial pulmonary fibrosis, dilated cardiomyopathy, discoid lupus , diseases involving leukocyte diapedesis, Dressler's syndrome, Dupuytren's contracture, echovirus infection, eczema including allergic or atopic eczema, encephalitis such as Rasmussen's encephalitis and limbic encephalitis and / or brainstem encephalitis lyco, encephalomyelitis, optionally allergic encephalomyelitis and experimental allergic encephalomyelitis (EAE), endarterial hyperplasia, endocarditis, endocrine ophthalmopathy, endometriosis, endomyocardial fibrosis, phacoanaphylactic enophthalmia, endophthalmitis, allergic enteritis, eosinophilia-myalgia syndrome, eosinophilic fasciitis, epidemic keratoconjunctivitis (bullous epidermolysis acquisita EBA), episclera, episcleritis, Epstein-Barr virus infection, erythema elevatum and diutium, erythema multiforme, erythema nodosum leprous, erythema nodosum, erythroblastosis fetalis, esophageal dysmotility, essential mixed cryoglobulinemia, ethmoid, Evan's syndrome, experimental allergic encephalomyelitis (EAE), factor VIII deficiency, farmers' lung disease, rheumatic fever, Felty's syndrome, fibromyalgia, fibrosing alveolitis, filariasis, focal segmental glomerulosclerosis (FSGS), food poisoning, frontal, gastric atrophy, giant cell arthritis (arthritis tem poral), giant cell hepatitis, polymyalgia giant cell, glomerulonephritis, glomerulonephritis (GN) with and without nephrotic syndrome such as chronic or acute glomerulonephritis (e.g. primary GN), Goodpasture syndrome, gouty arthritis, transfusion-associated syndromes granulocytes, granulomatosis including lymphomatoid granulomatosis, granulomatosis with polyangiitis (GPA), granulomatous uveitis, Grave's disease, Guillain-Barré syndrome, guttate psoriasis, paroxysmal hemoglobinuria, Hamman-Rich disease, Hashimoto's disease, Hashimoto's thyroiditis, hemochromatosis, hemolytic anemia or immune hemolytic anemia, including autoimmune hemolytic anemia (AIHA), hemolytic anemia, hemophilia A, Henoch-Schonlein purpura, herpes gestationis, human immunodeficiency virus (HIV) infection, hyperalgesia, hypogammaglobulinemia, hypogonadism, hypoparathyroidism , idiopathic diabetes insipidus, idiopathic facial palsy, hypothyroidism idiopathic idism, idiopathic IgA nephropathy, idiopathic membranous GN or idiopathic membranous nephropathy, idiopathic nephritic syndrome, idiopathic pulmonary fibrosis, idiopathic sprue, idiopathic thrombocytopenic purpura (ITP), IgA nephropathy, IgE-mediated diseases, optionally anaphylaxis and allergic or atopic rhinitis, lgG4-related sclerosing disease regional ileitis, zncRan / nznz / q / Yi immune complex nephritis,Cytokine- and T-lymphocyte-mediated immune responses associated with acute and delayed hypersensitivity, immune-mediated GN, immunoregulatory lipoproteins, including adult or acute respiratory distress syndrome (ARDS), inclusion body myositis, infectious arthritis, infertility due to antisperm antibodies, total or partial inflammation of the uvea, inflammatory bowel disease (IBD), hyperproliferative inflammatory skin diseases, inflammatory myopathy, insulin-dependent diabetes (type 1), insulitis, interstitial cystitis, interstitial lung disease, interstitial pulmonary fibrosis, iritis , ischemic perfusion disorder, joint inflammation, juvenile arthritis, juvenile dermatomyositis, juvenile diabetes, juvenile-onset diabetes mellitus (Type I), including pediatric insulin-dependent diabetes mellitus (IDDM), juvenile-onset rheumatoid arthritis, Kawasaki syndrome, keratoconjunctivitis sec a, kypanosomiasis, Lambert-Eaton syndrome, leishmaniasis, leprosy, leukopenia, leukocyte adhesion deficiency, leukocytoclastic vasculitis, leukopenia, lichen planus, lichen sclerosus, ligneous conjunctivitis, linear IgA dermatosis, linear IgA disease (LAD), Loffler syndrome, lupoid hepatitis, lupus (including nephritis, cerebritis, pediatric, non-renal, extra-renal, discoid, alopecia), lupus (SLE), disseminated lupus erythematosus, Lyme arthritis, Lyme disease, lymphoid interstitial pneumonitis, malaria, autoimmune infertility male and female, medium-vessel vasculitis (including Kawasaki disease and polyarteritis nodosa), membranous or membranous proliferative GN (MPGN), including Type I and Type II, and rapidly progressive GN, membranous GN (membranous nephropathy) , Meniere's disease, meningitis, microscopic colitis, microscopic polyangiitis, migraine, minimal change nephropathy, mixed connective tissue disease (MCTD), mononuc infectious leosis, Mooren's ulcer, Mucha-Habermann's disease, multifocal motor neuropathy, multiple endocrine failure, multiple organ injury syndrome such as those secondary to sepsis, trauma or hemorrhage, multiple organ injury syndrome, multiple sclerosis (MS) such as spinooptic MS , multiple sclerosis, mumps, muscular disorders, myasthenia gravis such as thymoma-associated myasthenia gravis, myasthenia gravis, myocarditis, myositis, narcolepsy, necrotizing enterocolitis and transmural colitis, and autoimmune inflammatory bowel disease, necrotizing, cutaneous or hypersensitivity vasculitis, neonatal lupus syndrome (NLE), nephrosis, nephrotic syndrome, neurological syndrome, neuromyelitis optica (Devic), neuromyelitis optica, neuromyotonia, neutropenia, noncancerous lymphocytosis, nongranulomatous uveitis, nonmalignant thymoma, ocular and orbital inflammatory disorders, ocular scarring pemphigoid, oophoritis, ophthalmia sympathetic, opso syndrome myoclonic clonus (QMS), opsoclonus or myoclonic opsoclonus syndrome (QMS), and sensory neuropathy, optic neuritis, granulomatous orchitis, osteoarthritis, palindromic rheumatism, pancreatitis, pancytopenia, PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus), paraneoplastic cerebellar degeneration, paraneoplastic syndrome, paraneoplastic syndromes, including paraneoplastic neurological syndromes, optionally Lambert-Eaton myasthenic syndrome or Eaton-Lambert syndrome, parasitic diseases such as Leishmania, paroxysmal nocturnal hemoglobinuria (PNH), Parry Romberg syndrome, pars planitis (peripheral uveitis), Parsonnage-Turner syndrome, parvovirus infection, pemphigoid such as bullous pemphigoid and cutaneous pemphigoid, pemphigus (including pemphigus vulgaris), zncRan / nznz / q / Yi erythematous pemphigus, pemphigus foliaceus, pemphigus, mucous membrane, pemphigoid, pemphigus, peptic ulcer , periodic paralysis, peripheral neuropathy, enceph perivenous allomyelitis, pernicious anemia (pernicious anemia), pernicious anemia, facoa neurogenic uveitis, pneumoncirrhosis, POEMS syndrome, polyarteritis nodosa, Types I, II, and III, primary chronic polyarthritis, polychondritis (eg, refractory or relapsing polychondritis), polyendocrine autoimmune disease , polyendocrine failure, polyglandular syndromes, optionally autoimmune polyglandular syndromes (or polyglandular endocrinopathy syndromes),polymyositis / dermatomyositis, polyneuropathies, polyradiculitis acuta, post-cardiotomy syndrome, posterior uveitis or autoimmune uveitis, postmyocardial infarction syndrome, postpericardiotomy syndrome, post-streptococcal nephritis, post-vaccination syndromes, presenile dementia, primary biliary cirrhosis, primary hypothyroidism, idiopathic myxedema primary, primary lymphocytosis, including monoclonal B-cell lymphocytosis, optionally benign monoclonal gammopathy and monoclonal gammopathy of undetermined significance, MGUS, primary myxedema, primary progressive MS (PPMS) and relapsing-remitting MS (RRMS), primary sclerosing cholangitis, progesterone dermatitis, progressive systemic sclerosis, proliferative arthritis, psoriasis such as plaque psoriasis, psoriasis, psoriatic arthritis, pulmonary alveolar proteinosis, pulmonary infiltration eosinophilia, pure red cell aplasia or anemia (PRCA), pure red cell aplasia, purulent or non-purulent sinusitis, psoriasis pus tular and nail psoriasis, pyelitis, pyoderma gangrenosum, de Quervain's thyroiditis, Raynaud's phenomenon, reactive arthritis, recurrent miscarriage, reduced blood pressure response, reflex sympathetic dystrophy, refractory sprain, Reiter's disease or syndrome, recurrent polychondritis , reperfusion injury to myocardium or other tissues, reperfusion injury, respiratory distress syndrome, restless legs syndrome, retinal autoimmunity, retroperitoneal fibrosis, Reynaud's syndrome, rheumatic diseases, rheumatic fever, rheumatism, rheumatoid arthritis, rheumatoid spondylitis, infection by rubella virus, Sampter syndrome, sarcoidosis, schistosomiasis, Schmidt syndrome, SCID and Epstein-Barr virus-associated diseases, sclera, scleritis, sclerodactyl, scleroderma, optionally systemic scleroderma, sclerosing cholangitis, disseminated sclerosis, sclerosis such as systemic sclerosis , sensorineural hearing loss, spondyloart seronegative ritis, Sheehan's syndrome, Shulman's syndrome, silicosis, Sjógren's syndrome, sperm and testicular autoimmunity, sphenoid sinusitis, Stevens-Johnson syndrome, stiff man (or stiff person) syndrome, subacute bacterial endocarditis (SBE), lupus erythematosus subacute cutaneous, sudden hearing loss, Susac syndrome, Sydenham's chorea, sympathetic ophthalmia, systemic lupus erythematosus (SLE) or systemic lupus erythematosus, cutaneous SLE, systemic necrotizing vasculitis, ANCA-associated vasculitis, optionally vasculitis or Churg-Strauss syndrome ( CSS), dorsal septa, Takayasu's arteritis, telangiectasia, temporal arteritis / giant cell arteritis, thromboangiitis ubiterans, thrombocytopenia, including thrombotic thrombocytopenic purpura (TTP), and autoimmune- or immune-mediated thrombocytopenia, such as idiopathic thrombocytopenic purpura (ITP). ), including chronic or acute ITP, thrombocytopenic purpura (TTP), thyrotoxicosis, tissue injury, Tolosa-Hunt syndrome, toxic epidermal necrolysis, toxic shock syndrome, transfusion reaction, transient hypogammaglobulinemia of infancy, transverse myelitis, transverse myelitis, tropical pulmonary eosinophilia, tuberculosis, zncRan / nznz / q / Yi ulcerative colitis , undifferentiated connective tissue disease (UCTD), urticaria, optionally chronic allergic urticaria and chronic idiopathic urticaria, including chronic autoimmune anterior urticaria, uveitis, uveoretinitis, valvulitis, vascular dysfunction, vasculitis, vertebral arthritis, vesiculobullous dermatosis, vitiligo, Wegener's granulomatosis (granulomatosis with polyangiitis (GPA)), Wiskott-Aldrich syndrome, or X-linked hyper IgM syndrome., It is to be understood that the disease conditions identified herein are intended to be exemplary and not exhaustive. According to at least some embodiments, anti-MCT1 antibodies, fragments, conjugates thereof, or a pharmaceutical composition comprising them, as described herein, that function to decrease MCT1-mediated lactose transport, can be used. to treat a disease related to the immune system. Optionally, the immune system-related condition comprises an immune system-related condition, autoimmune diseases as mentioned herein, lupus, transplant rejection, and graft-versus-host disease and / or to block activated T-lymphocytes and B-lymphocytes , immune system related diseases as mentioned herein and / or for immunotherapy (inhibition of immune stimulation). Optionally, the immune condition is selected from autoimmune disease, transplant rejection, inflammatory disease, allergic condition, or graft-versus-host disease. In a particular embodiment, the anti-MCT1 antibodies of the invention can be used to treat lupus. In one embodiment, the anti-MCT1 antibodies of the invention can be used to treat graft-versus-host disease (GVHD). In another embodiment, the anti-MCT1 antibodies of the invention can be used to treat graft rejection. In yet another embodiment, the anti-MCT1 antibodies of the invention can be used to treat type I diabetes. In one embodiment, the anti-MCT1 antibodies of the invention can be used to treat type II diabetes. In another embodiment, the anti-MCT1 antibodies of the invention can be used to treat obesity. In a particular embodiment, MCT1 Ab1 can be used to treat lupus. In one embodiment, MCT1 Ab1 can be used to treat graft-versus-host disease (GVHD). In another embodiment, MCT1 Ab1 can be used to treat graft rejection. In yet another embodiment, MCT1 Ab1 can be used to treat type I diabetes. In one embodiment, MCT1 Ab1 can be used to treat type II diabetes. In another embodiment, MCT1 Ab1 can be used to treat obesity. Likewise, in each of these embodiments, a variant or fusion protein can be used that comprises one or more CDRs of MCT1 Ab1. Optionally, the treatment is combined with another useful moiety for treating an immune condition, eg, metformin. Therefore, treatment of systemic lupus erythematosus, by use of the subject's antibodies, can be combined with, for example, any known therapeutic agent or method for treating systemic lupus erythematosus, optionally as described herein. Similarly, zncRan / nznz / q / Yi treatment of GVHD, through the use of the subject's antibodies, can be combined with, for example, any known therapeutic agent or method for treating GVHD, optionally as described herein. . The treatment of multiple sclerosis, through the use of the agents according to at least some embodiments of the present invention, can be combined with, for example, any known therapeutic agent or method for treating multiple sclerosis, optionally as described below. described herein. Similarly, treatment of rheumatoid arthritis or other arthritic condition, through the use of the subject's antibodies, can be combined with, for example, any therapeutic agent or method known to treat rheumatoid arthritis, optionally as described in present. In addition, the treatment of type 1 diabetes, through the use of the subject's antibodies, can be combined with, for example, any known therapeutic agent or method for treating type 1 diabetes, optionally as described herein. Treatment of psoriasis, through the use of the subject's antibodies, can be combined with, for example, any known therapeutic agent or method for treating psoriasis, optionally as described herein. In the treatments described above, for example, a subject with one of the autoimmune or inflammatory conditions mentioned above or others, will be administered an anti-MCT1 antibody described herein or an antigen-binding fragment according to the invention, which antibody suppresses activated T cells and / or B cells and / or production of proinflammatory cytokines that are involved in disease pathology, preventing or ameliorating disease symptoms and potentially resulting in prolonged disease remission, for example , due to the induction of Tregs causing tolerance to T lymphocytes or prolonged immunosuppression. Therapeutic agents and / or a pharmaceutical composition comprising them, as mentioned herein, according to at least some embodiments of the invention, can be administered as the sole active ingredient or together with other drugs in immunomodulatory regimens or other anti-inflammatory agents, for example for the treatment or prevention of acute or chronic allograft or xenograft rejection or inflammatory or autoimmune disorders, or to induce tolerance. cancer treatment The types of cancer that can be treated include tumors that are not vascularized, or not yet substantially vascularized, as well as vascularized tumors. Cancer types may comprise non-solid tumors (such as blood tumors, eg, leukemias and lymphomas) or may comprise solid tumors. Types of cancer to be treated with the antibodies of the invention include, but are not limited to, carcinoma, blastoma, and sarcoma, and certain lymphoid leukemias or malignancies, benign and malignant tumors, and malignant tumors, eg, sarcomas, carcinomas, and melanomas. Also included are adult tumors / cancers and pediatric tumors / cancers. zncAan / nznz / q / Yi Hematologic cancers are cancers of the blood or bone marrow. Examples of hematologic (or hematogenous) cancers include leukemias, including acute leukemias (such as acute lymphocytic leukemia, acute myelocytic leukemia, acute myelogenous leukemia, and myeloblastic, promyelocytic, myelomonocytic, monocytic, and erythroleukemias), leukemias (such as chronic myelocytic (granulocytic) leukemia), chronic myelogenous leukemia and chronic lymphocytic leukemia), polycythemia vera, lymphoma, Hodgkin's disease, non-Hodgkin's lymphoma (indolent and high-grade forms), multiple myeloma, Waldenstrom's macroglobulinemia, heavy chain, myelodysplastic syndrome, hairy cell leukemia, and myelodysplasia. Solid tumors are abnormal masses of tissue that usually do not contain cysts or fluid areas. Solid tumors can be benign or malignant. The different types of solid tumors are named for the type of cells that form them (such as sarcomas, carcinomas, and lymphomas). Examples of solid tumors, such as sarcomas and carcinomas, include fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteosarcoma and other sarcomas, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, lymphoid malignancy, pancreatic cancer, cancer breast, lung cancer, ovarian cancer, prostate cancer, hepatocellular carcinoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, medullary thyroid carcinoma, papillary thyroid carcinoma, pheochromocytomas sebaceous gland carcinoma , papillary carcinoma, papillary adenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, Wilms tumor, cervical cancer, testicular tumor, seminoma, bladder carcinoma, melanoma, and CNS tumors (such as a glioma (such as brain stem glioma and mixed gliomas), glioblastoma (also known as glioblastoma multiforme) astrocytoma, CNS lymphoma, germinoma, medulloblastoma, Schwannoma craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, neuroblastoma, retinoblastoma, and brain metastases). Preferably, the antibodies of the invention are used to treat a cancer where the tumor cells are positive for the expression of MCT1. In general, MCT1-positive tumor cells can be identified by known methods. For example, MCT1 expression in tumor cells can be identified by immunofluorescence or flow cytometry using the antibodies of the invention. Alternatively, MCT1 expression can be functionally measured by observing the inhibition by the inventive antibodies against the target cells. A biopsy is the removal of tissue and / or cells from an individual. Such extraction may be to harvest tissue and / or cells from the individual for the purpose of performing experiments on the extracted tissue and / or cells. This experimentation may include experiments to determine if the individual has and / or suffers from a certain condition or disease state. The condition or disease can be, for example, cancer. With respect to detecting the presence of MCT1-expressing tumor cells in a host, the sample comprising cells from the host may be a sample comprising whole, Used zncRan / nznz / q / Yi cells, or a fraction thereof. from whole cells, eg, a nuclear or cytoplasmic fraction, a whole protein fraction, or a nucleic acid fraction. If the sample comprises whole cells, the cells can be any cell of the host, for example, the cells of any organ or tissue, including blood cells or endothelial cells. Treatment of other conditions associated with MCT1, eg, EIHI The antibodies and antibody fragments of the invention may also be used to treat, prevent, or diagnose any other condition, disorder, or disease that involves MCT1 expression in healthy or diseased cells. For example, the invention also contemplates a method of treating or preventing EIHI in a subject, which method comprises administering antibodies or antibody fragments according to the invention. Modes of administration The compositions of the present invention can be administered in a number of ways depending on whether local or systemic treatment is desired. In general, administration can be topical, parenteral, or enteral. The compositions of the invention are typically suitable for parenteral administration. As used herein, parenteral administration of a pharmaceutical composition includes any route of administration characterized by physical disruption of a subject's tissue and administration of the pharmaceutical composition through a disruption in the tissue, generally resulting in as a result of direct administration into the bloodstream, into muscle or into an internal organ. Thus, parenteral administration includes, but is not limited to, administration of a pharmaceutical composition by injection of the composition, by application of the composition through a surgical incision, by application of the composition through an unopened wound. tissue-penetrating surgical, and the like. In particular, parenteral administration is contemplated to include, but is not limited to, subcutaneous, intraperitoneal, intramuscular, intrasternal, intravenous, intraarterial, intrathecal, intraventricular, intraurethral, ​​intracranial, intratumoral, intrasynovial injection or infusion; and renal dialysis infusion techniques. In a preferred embodiment, parenteral administration of the compositions of the present invention comprises subcutaneous or intraperitoneal administration. In general, pharmaceutical composition formulations suitable for parenteral administration comprise the active ingredient combined with a pharmaceutically acceptable carrier, such as sterile water or sterile isotonic saline. Such formulations may be prepared, packaged or sold in a form suitable for bolus administration or continuous administration. Injectable formulations may be prepared, packaged, or sold in unit dose form, such as in ampoules or multidose containers that contain a preservative. Formulations for parenteral administration include, but are not limited to, suspensions, solutions, emulsions in oily or aqueous vehicles, pastes, and the like. Such formulations may further comprise one or more additional ingredients including, but not limited to, zncAan / nznz / q / Yi suspending, stabilizing or dispersing agents. In one embodiment of a formulation for parenteral administration, the active ingredient is provided in dry (i.e., powdered or granular) form for reconstitution with a suitable vehicle (for example, sterile pyrogen-free water) prior to administration. parenteral administration of the reconstituted composition. Parenteral formulations also include aqueous solutions that may contain excipients such as salts, carbohydrates, and buffering agents (for example, at pH 3 to 9), but, for some applications, may more suitably be formulated as a sterile non-aqueous solution or as a dry form for use in conjunction with a suitable vehicle such as sterile pyrogen-free water. Exemplary parenteral administration forms include solutions or suspensions in sterile aqueous solutions, for example, aqueous propylene glycol or dextrose solutions. Such dosage forms can be suitably buffered, if desired. Other parental delivery formulations that are useful include those that comprise the active ingredient in microcrystalline form, or in a liposomal preparation. Formulations for parenteral administration may be formulated to be immediate and / or modified release. Modified release formulations include delayed, sustained, pulsed, controlled, targeted and programmed release. The terms oral, enteral, enterally, orally, non-parenterally, non-parenterally, and the like, refer to the administration of a compound or composition to an individual by a route or mode along the alimentary canal. Examples of oral routes of administration of a composition include, but are not limited to, ingestion of liquid or solid forms of a composition from the mouth, administration of a composition through a nasojejunal or gastrostomy tube, intraduodenal administration of a composition and rectal administration, for example, through the use of suppositories to the lower intestinal tract of the alimentary canal. Preferably, the formulated composition comprising isolated anti-MCT1 antibodies or antibody fragments is suitable for administration by injection. Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, aerosols, liquids, semi-solids, single-phase compositions, multi-phase compositions (eg, oil-in-water, water-in-oil), foams, microsponges, liposomes, nanoemulsions, spray foams, polymers, fullerenes, and powders. Conventional pharmaceutical carriers, aqueous, powder or oil bases and thickeners may be necessary or desirable. Compositions and formulations for oral administration include powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets, or tablets. Thickeners, flavoring agents, diluents, emulsifiers, dispersing or binding agents may be desirable. Compositions and formulations for parenteral, intrathecal, or intraventricular administration may include sterile aqueous solutions which may also contain suitable buffers, diluents, and other additives such as, but not limited to, penetration enhancers, carding compounds, and other physically acceptable carriers or excipients. from a pharmaceutical point of view. zncRan / nznz / q / Yi The pharmaceutical compositions of the present invention include, among others, solutions, emulsions, and formulations containing liposomes. These compositions can be generated from a variety of components including, but not limited to, preformed liquids, self-emulsifying solids, and self-emulsifying semisolids. The pharmaceutical compositions of the present invention, which may conveniently be presented in unit dose form, may be prepared in accordance with conventional techniques well known in the pharmaceutical industry. Such techniques include the step of associating the active ingredients with the pharmaceutical carrier(s) or excipient(s). In general, formulations are prepared by thoroughly and uniformly mixing the active ingredients with liquid carriers, finely divided solid carriers, or both, and then, if necessary, shaping the product. The compositions of the present invention may be formulated in any of many possible dosage forms, such as, but not limited to, tablets, capsules, liquid syrups, soft gels, suppositories, aerosols, and enemas. The compositions of the present invention may also be formulated as suspensions in aqueous, non-aqueous, or mixed media. Aqueous suspensions may further contain substances that increase the viscosity of the suspension, including, for example, sodium carboxymethylcellulose, sorbitol and / or dextran. The suspension may also contain stabilizers. In one embodiment of the present invention, the pharmaceutical compositions can be formulated and used as foams. Pharmaceutical foams include formulations such as, but not limited to, emulsions, microemulsions, creams, jellies, and liposomes. Although basically similar in nature, these formulations vary in the components and consistency of the final product. Agents that enhance oligonucleotide uptake at the cellular level may also be added to the pharmaceutical and other compositions of the present invention. For example, cationic lipids, such as lipofectin (US Patent No. 5,705,188), cationic glycerol derivatives, and polycationic molecules, such as polylysine (WO 97 / 30731), also enhance cellular uptake of oligonucleotides. The compositions of the present invention may additionally contain other adjunct components that are conventionally found in pharmaceutical compositions. Thus, for example, the compositions may contain additional compatible pharmaceutically active materials, such as, for example, antipruritics, astringents, local anesthetics, or anti-inflammatory agents, or may contain additional materials useful for physically formulating various dosage forms of the compositions herein. invention, such as dyes, flavoring agents, preservatives, antioxidants, opacifiers, thickening agents, and stabilizers. However, such materials, when added, should not unduly interfere with the biological activities of the components of the compositions of the present invention. Formulations can be sterilized and, if desired, mixed with auxiliaries, e.g. lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts to influence osmotic pressure, buffers, zncRan / nznz / q / Yi colorants, flavors and / or aromatic substances and the like that do not deleteriously interact with the nucleic acid(s) in the formulation. Formulations comprising anti-MCT1 antibodies or antigen-binding fragments thereof may include pharmaceutically acceptable excipients. The excipients included in the formulations will have different purposes depending on, for example, the antibody and the mode of administration. Examples of excipients generally used include, but are not limited to: saline, buffered saline, dextrose, water for infection, glycerol, ethanol, and combinations thereof, stabilizing agents, solubilizing agents, and surfactants, buffers, and preservatives, tonicity agents, fillers and lubricating agents. Formulations comprising anti-MCT1 antibodies will typically have been prepared and cultured in the absence of non-human components, such as animal serum (eg, bovine serum albumin). The formulation or composition may also contain more than one active ingredient useful for the particular indication, disease or condition being treated with the binding molecules or cells, for example, those with complementary activities to the binding molecule or cell, where the respective activities do not negatively affect each other. Such active ingredients are suitably present in combination in amounts that are effective for the intended purpose. Thus, in some embodiments, the pharmaceutical composition further includes other pharmaceutically active agents or drugs, such as chemotherapeutic agents, for example, asparaginase, busulfan, carboplatin, cisplatin, daunorubicin, doxorubicin, fluorouracil, gemeitabine, hydroxyurea, methotrexate, paclitaxel, rituximab, vinblastine, vincristine, etc. In some embodiments, the pharmaceutically active agents or drugs may comprise immune checkpoint inhibitors, for example, drugs that target PD-1, PD-L1, PD-L2, LAG3, CTLA4, KIR, CD244, B7 -H3, B7-H4, BTLA, HVEM, GAL9, TIM3 and / or A2aR. Examples of these inhibitors include, but are not limited to, pidilizumab, nivolumab, pembrolizumab, atezolizumab, MDX-1105, BMS-936559, MEDI4736, MPDL3280A, MSB0010718C, tremelimumab, and ipilimumab, which may be administered alone or in combination with other agents, eg, GM-CSF. The antibodies can be combined with other treatments that can be administered in the same or different compositions, at the same time or at different times and in any order. For example, the antibodies of the invention can be administered in a therapeutic regimen that includes administration of a PD-1 or PD-L1 agonist, CTLA4-lg, a cytokine, a cytokine agonist or antagonist, or other receptor agonist or antagonist. . The pharmaceutical composition in some aspects may employ extended release, retarded release and sustained release systems such that administration of the composition occurs before and with sufficient time to cause sensitization of the site to be treated. There are many types of release delivery systems available and known. Such systems can avoid repeated administrations of the composition, thus increasing convenience for the subject and the physician. zncAan / nznz / q / Yi Dose The pharmaceutical composition in some embodiments contains the anti-MCT1 antibodies or antibody fragments in amounts effective to treat or prevent the disease or condition, such as a therapeutically effective or prophylactically effective amount. Therapeutic or prophylactic efficacy in some embodiments is monitored by periodic evaluation of treated subjects. For repeated administrations over several days or more, depending on the condition, the treatment is repeated until the desired suppression of disease symptoms occurs. However, other dosage regimens may be useful and can be determined. The desired dose can be administered by a single bolus administration of the composition, by multiple bolus administrations of the composition, or by continuous infusion administration of the composition. The antibodies or antibody fragments can be administered in one or more doses. In some embodiments, said effective amount of antibody can be administered as a single dose. In some embodiments, said effective amount of antibody may be administered as more than one dose over a period of time. The timing of administration is at the discretion of the attending physician and depends on the clinical condition of the patient. While individual needs vary, determination of optimal ranges of effective amounts of a given antibody for a particular disease or conditions is within the purview of the mid-level trade. An effective amount means an amount that provides a therapeutic or prophylactic benefit. The dose administered will depend on the age, health and weight of the recipient, the type of concurrent treatment, if any, the frequency of treatment and the nature of the desired effect. In some embodiments, an effective amount of antibodies or composition comprising those antibodies is administered parenterally. In some embodiments, the administration may be an intravenous administration. In some embodiments, administration can be done directly by injection into a disease site. For purposes of the invention, the amount or dose of the antibodies of the invention administered should be sufficient to effect a therapeutic or prophylactic response in the subject or animal for a reasonable period of time. For example, the dose of the antibody of the invention should be sufficient to bind to the antigen, or detect, treat or prevent the disease in a period of about 2 hours or more, for example, about 12 to about 24 or more hours. , from the moment of administration. In certain embodiments, the time period could be even longer. The dose will be determined by the efficacy of the particular antibody and the condition of the animal (eg, human) as well as the body weight of the animal (eg, human) to be treated. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will vary depending on the subject to be treated and the particular mode of administration. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will generally be the amount of the composition that produces a therapeutic effect. Generally, one hundred percent, this amount will range from about 0.01 percent to about ninety-nine percent zncRan / nznz / q / YiAi of the active ingredient, for example, from about 0.1 percent to about 70 percent most, for example, between about 1 percent and about 30 percent active ingredient in combination with a pharmaceutically acceptable carrier. Dosage regimens are adjusted to provide the optimal response desired (eg, a therapeutic effect). For example, a single bolus may be administered, multiple divided doses may be administered over time, or the dose may be proportionally reduced or increased as dictated by the exigencies of the therapeutic situation. In particular, it is desirable to formulate parenteral compositions in unit dose form for ease of administration and uniformity of dose. As used herein, "unit dosage form" refers to physically separate units useful as unit doses to the subjects to be treated; each unit contains a predetermined amount of active compound, calculated to produce the desired therapeutic effect in combination with the required pharmaceutical carrier. The specification of unit dosage forms according to at least some embodiments of the present invention is dictated by and is directly dependent on (a) the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and (b) the limitations inherent to the formulation technique of said active compound for the treatment of sensitivity in individuals. For administration of the anti-MCT1 antibody, or an antigen-binding fragment thereof, disclosed herein, the dose ranges from about 0.0001 to 100 mg / kg, and more usually 0.01 to 5 mg / kg, of body weight. host body. For example, doses may be 0.3 mg / kg body weight, 1 mg / kg body weight, 3 mg / kg body weight, 5 mg / kg body weight, or 10 mg / kg body weight or within the range of 1-10 mg / kg. An exemplary treatment regimen involves administration once a week, once every two weeks, once every three weeks, once every four weeks, once a month, once every 3 months, or once every three to 6 months. . Preferred dose regimens for an antibody disclosed herein in accordance with at least some embodiments of the present invention include 1 mg / kg of body weight or 3 mg / kg of body weight by intravenous administration, and the antibody disclosed in this is administered using one of the following dosing schedules: (i) every four weeks for six doses, then every three months; (ii) every three weeks; (iii) 3 mg / kg of body weight once followed by 1 mg / kg of body weight every three weeks. In some methods, two or more monoclonal antibodies with different binding specificities are administered simultaneously, in which case the dose of each antibody disclosed herein administered falls within the indicated ranges. The antibody disclosed herein is generally administered on multiple occasions. Intervals between single doses can be, for example, daily, weekly, monthly, quarterly, or annually. The intervals may also be irregular as indicated by measurement of the blood levels of antibodies against the target antigen in the patient. In some methods, the dose is adjusted to achieve a plasma antibody concentration around 1-1000 pg / ml and in some methods around 25-300 pg / ml. zncRan / nznz / q / Yi Alternatively, a therapeutic agent may be administered as a sustained release formulation, in which case less frequent administration is required. The dose and frequency vary according to the half-life of the therapeutic agent in the patient. In general, human antibodies show the longest half-life, followed by humanized antibodies, chimeric antibodies, and non-human antibodies. The half-life of fusion proteins can vary widely. The dose and frequency of administration may vary depending on whether the treatment is prophylactic or therapeutic. In prophylactic applications, a relatively low dose is administered at relatively infrequent intervals over a long period of time. Some patients continue to receive treatment for the rest of their lives. In therapeutic applications, a relatively high dose is sometimes required at relatively short intervals until the progression of the disease is slowed or terminated, and for example, until the patient shows partial or complete improvement in the symptoms of the disease. Thereafter, the patient can be administered a prophylactic regimen. The actual dose levels of the active ingredients in the pharmaceutical compositions of the present invention can be varied to obtain an amount of the active ingredient that is effective in achieving the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. The dose level selected will depend on a variety of pharmacokinetic factors including the activity of the particular compositions of the present invention employed, or the ester, salt or amide thereof, the route of administration, the time of administration, the rate of excretion of particular compound employed, duration of treatment, other drugs, compounds, and / or materials used in combination with the particular compositions employed, age, sex, weight, condition, general health, and prior medical history of the patient being treated, and similar factors well known in medical practice. In some embodiments, the antibodies are administered as part of a concomitant treatment, such as simultaneously or sequentially, in any order, another therapeutic intervention, such as another antibody or genetically engineered cell or receptor or agent, such as a cytotoxic or therapeutic. The antibodies in some embodiments are administered in conjunction with one or more additional therapeutic agents or in connection with another therapeutic intervention, either simultaneously or sequentially in any order. In some settings, the antibodies are co-administered with another therapy close enough in time that the antibodies enhance the effect of one or more additional therapeutic agents, or vice versa. In some embodiments, the antibodies are administered prior to the one or more additional therapeutic agents. In some embodiments, the antibodies are administered after the one or more additional therapeutic agents. variations Included within the scope of the invention are functional portions of the antibodies of the invention described herein. The term functional portion when used in reference to a zncAan / nznz / q / Yi antibody refers to any part or fragment of the antibody of the invention, which part or fragment retains the biological activity of the antibody of which it is a part (the parent antibody ). Functional portions encompass, for example, those parts of an antibody that retain the ability to recognize target cells, or detect, treat, or prevent disease, to a similar degree, the same degree, or to a greater extent, as the parent antibody. Referring to the parent antibody, the functional portion may comprise, for example, about 10%, 25%, 30%, 50%, 68%, 80%, 90%, 95% or more of the parent antibody. The functional portion may comprise additional amino acids at the amino or carboxyl terminus of the portion, or at both termini, which additional amino acids are not found in the amino acid sequence of the parent antibody. Conveniently, the additional amino acids do not interfere with the biological function of the functional portion, eg, recognizing target cells, detecting cancer, treating or preventing cancer, etc. More conveniently, the additional amino acids enhance the biological activity, compared to the biological activity of the parent antibody. Functional variants of the antibodies of the invention described herein are included within the scope of the invention. The term functional variant, as used herein, refers to an antibody, polypeptide, or protein that has substantial or significant sequence identity or similarity to a parent antibody, which functional variant retains the biological activity of the antibody of which it is a parent antibody. variant. Functional variants encompass, for example, those variants of the antibody described herein (the parent antibody) that retain the ability to recognize target cells to a similar degree, the same degree, or to a greater extent than the parental antibody. Referring to the parent antibody, the functional variant can be, for example, at least about 30%, 50%, 75%, 80%, 90%, 98% or more identical in amino acid sequence to the parent antibody. A functional variant may, for example, comprise the amino acid sequence of the parent antibody with at least one conservative amino acid substitution. Additionally or alternatively, functional variants may comprise the amino acid sequence of the parent antibody with at least one non-conservative amino acid substitution. In this case, it is preferred that the non-conservative amino acid substitution does not interfere or inhibit the biological activity of the functional variant. The non-conservative amino acid substitution can enhance the biological activity of the functional variant, such that the biological activity of the functional variant is increased compared to the parental antibody. Amino acid substitutions of the antibodies of the invention are, for example, conservative amino acid substitutions. Conservative amino acid substitutions are known in the art and include amino acid substitutions in which an amino acid having certain physical and / or chemical properties is exchanged for another amino acid having the same chemical or physical properties. For example, the conservative amino acid substitution can be an acidic / negatively charged polar amino acid substituted with another acidic / negatively charged polar amino acid (for example, Asp or Glu), an amino acid with a nonpolar side chain substituted with another amino acid with a non-polar side chain (e.g. Ala, Gly, Val, lie, Leu, Met, Phe, Pro, Trp, Cys, Val, etc.), a zncAan / nznz / q / Yi polar basic / positively charged amino acid substituted by another polar basic / positively charged amino acid (e.g. Lys, His, Arg, etc.), an uncharged amino acid with a polar side chain substituted by another uncharged amino acid with a polar side chain (e.g. Asn, Gln, Ser, Thr, Tyr, etc.), an amino acid with a beta-branched side chain substituted by another amino acid with a beta-branched side chain (for example, lie, Thr and Val), an amino acid with an aromatic side chain substituted by another amino acid with an aromatic side chain (for example, His, P he, Trp and Tyr), etc. Also, amino acids can be added or removed from the sequence depending on the vector design. The antibody may consist essentially of the specified amino acid sequence(s) described herein such that other components, eg, other amino acids, do not materially change the biological activity of the functional variant. Antibodies of embodiments of the invention (including functional portions and functional variants) can be of any length, that is, they can comprise any number of amino acids, as long as the antibodies (or functional portions or functional variants thereof) retain their biological activity, eg, the ability to specifically bind to antigen, detect diseased cells in a mammal, or treat or prevent disease in a mammal, etc. For example, the antibody can be from about 50 to about 5000 amino acids in length, such as 50, 70, 75, 100, 125, 150, 175, 200, 300, 400, 500, 600, 700, 800, 900, 1000 or more amino acids in length. Antibodies of embodiments of the invention (including functional portions and functional variants of the invention) may comprise synthetic amino acids in place of one or more naturally occurring amino acids. Such synthetic amino acids are known in the art and include, for example, aminocyclohexane carboxylic acid, norleucine, α-amino n-decanoic acid, homoserine, Sacetylaminomethyl-cysteine, trans-3- and trans-4-hydroxyproline, 4-aminophenylalanine, 4 -nitrophenylalanine, 4-chlorophenylalanine, 4-carboxyphenylalanine, β-phenylserine β-hydroxyphenylalanine, phenylglycine, a-naphthylalanine, cyclohexylalanine, cyclohexylglycine, indoline-2-carboxylic acid, 1,2,3,4-tetrahydroisoquinolin-3-carboxylic acid , aminomalonic acid, aminomalonic acid monoamide, N'-benzyl-N'-methyl-lysine, N',N'dibenzyl-lysine, 6-hydroxylysine, ornithine, α-aminocyclopentane carboxylic acid, α-aminocyclohexane carboxylic acid, α-acid -aminocycloheptane carboxylic acid, a-(2-amino-2-norbornane)-carboxylic acid, α,γ-diaminobutyric acid, α,β-diaminopropionic acid, homophenylalanine and a-tert-butylglycine. Antibodies of embodiments of the invention (including functional moieties and functional variants) may be glycosylated, amidated, carboxylated, phosphorylated, esterified, Nacylated, cyclized through, for example, a disulfide bond, or converted to a salt. acid addition and / or optionally dimerized or polymerized, or conjugated. Antibodies of embodiments of the invention (including functional portions and functional variants thereof) can be obtained by methods known in the art. Antibodies can be made by any suitable method for making polypeptides or proteins. Suitable methods for synthesizing de novo polypeptides and proteins are described in zncRan / nznz / q / Yi references, such as Chan et al., Fmoc Solid Phase Peptide Synthesis, Oxford University Press, Oxford, UK, 2000; Peptide and Protein Drug Analysis, ed. Reid, R., Marcel Dekker, Inc., 2000; Epitope Mapping, ed. Westwood et al., Oxford University Press, Oxford, UK, 2001; and US Patent No. 5,449,752. Furthermore, polypeptides and proteins can be produced recombinantly using the nucleic acids described herein by standard recombinant methods. See, for example, Sambrook et al., Molecular Cloning: A Laboratory Manual, 3rd ed., Cold Spring Harbor Press, Cold Spring Harbor, NY 2001; and Ausubel et al., Current Protocols in Molecular Biology, Greene Publishing Associates and John Wiley & Sons, NY, 1994. In addition, some of the antibodies of the invention (including functional portions and functional variants thereof) can be isolated and / or purify from a source, such as a plant, a bacterium, an insect, a mammal, eg a rat, a human, etc. Isolation and purification methods are well known in the art. Alternatively, companies can commercially synthesize the antibodies described herein (including functional portions and functional variants thereof). In this regard, the antibodies of the invention can be synthetic, recombinant, isolated and / or purified. Antibodies having Vh and Vl sequences disclosed herein can be used to create novel variant antibodies by modifying the Vh and / or Vl sequences, or the constant region(s) attached thereto. Therefore, the structural features of a variant antibody of the invention are used to create structurally related variant antibodies that retain at least one functional property of the antibodies of the invention, such as binding to MCT1. For example, one or more CDR regions of a vacant anti-MCT1 antibody, eg, one of Ab1-Ab95 or mutations thereof, can be recombinantly combined with known framework regions and / or other CDRs to create anti-MCT1 antibodies. additional engineered (eg, antibodies that bind to MCT1) of the invention, as discussed herein. The starting material for the engineering method can be one or more of the Vh and / or Vl sequences provided herein, or one or more CDR regions thereof. To create the engineered antibody, it is not necessary to actually prepare (ie, express as a protein) an antibody having one or more of the Vh and / or Vl sequences provided herein, or one or more CDR regions of are. Instead, the information contained in the sequence(s) is used as a starting material to create a second generation sequence(s) derived from the original sequence(s) and then the second generation sequence(s) are prepared and expressed as a protein. Standard molecular biology techniques can be used to prepare and express altered antibody sequences. The antibody encoded by the altered antibody sequence(s) may retain one, some, or all of the functional properties of anti-MCT1 antibodies produced by methods and with sequences provided herein, which functional properties include binding to the MCT1 variant or MCT1 variant conjugated to a specific Kd level or less and / or modulation of immune cell activity, and / or selective binding to desired target cells, such as, for example, activated T-lymphocytes or B-lymphocytes. The functional properties of the altered zncRan / nznz / q / Yi antibodies can be assessed by standard assays available in the art and / or described herein. Mutations can be randomly or selectively introduced throughout or all of an anti-MCT1 antibody coding sequence and the resulting modified anti-MCT1 antibodies can be screened for binding activity and / or other desired functional properties. DEFINITIONS Unless otherwise defined, all technical and scientific terms used herein have the same meaning as is commonly given by a mid-level trade person to whom this invention pertains. Although methods and materials similar or equivalent to those described herein may be used in the invention or tests of the present invention, suitable methods and materials are described herein. Furthermore, the materials, methods, and examples are illustrative only and are not intended to be limiting. The nomenclatures used in connection with analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein, as well as laboratory procedures and techniques, are those known and commonly used in the art. Standard techniques are used for chemical syntheses, chemical analyses, pharmaceutical dispensing, formulation and preparations, and patient treatment. As used herein, a "5' cap" (also called an RNA cap, 7-methylguanosine RNA cap, or m7G RNA cap) is a modified guanine nucleotide that has been added to the leading or 5' end. ” of a eukaryotic messenger RNA shortly after the start of transcription. The 5' cap consists of an end group that is linked to the first transcribed nucleotide. Its presence is essential for recognition by the ribosome and protection against RNases. Capping is coupled to transcription, and occurs transcriptionally in tandem, such that each influences the other. Shortly after the start of transcription, the 5' end of the mRNA being synthesized is capped by a cap synthesis complex associated with RNA polymerase. This enzyme complex catalyzes the chemical reactions that are required for mRNA protection. The synthesis proceeds as a multi-step biochemical reaction. The cap portion can be modified to modulate the functionality of the mRNA such as its stability or efficiency of translation. As used in the description herein and in all of the claims that follow, the meaning of a, an and the includes a plural reference unless the context clearly indicates otherwise. Allergic disease, as used herein, broadly refers to a disease involving allergic reactions. More specifically, an allergic disease is defined as a disease for which an allergen is identified, where there is a strong correlation between exposure to that allergen and the onset of pathologic change, and where that pathologic change has been shown to have an immunological mechanism. . Here, an immunological mechanism means that leukocytes display an immune response to allergen stimulation. zncRan / nznz / q / Yi The term allogeneic or donor-derived refers to any material derived from a different animal of the same species as the individual to which the material is introduced. Two or more individuals are said to be allogeneic to each other when the genes at one or more loci are not identical. In some aspects, allogeneic material from individuals of the same species may be sufficiently different in genetics to interact antigenically. The term "amino acid", as used herein, refers to natural and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function similarly to natural amino acids. Natural amino acids are those that are encoded by the genetic code, as well as those amino acids that are subsequently modified (eg, hydroxyproline, γ-carboxyglutamate, and O-phosphoserine). Amino acid analogues refer to compounds that have the same basic chemical structure as a natural amino acid (i.e., a hydrogen-binding carbon, a carboxyl group, an amino group) and an R group (for example, homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium). Analogs can have modified R groups (eg, norleucine) or modified peptide backbones, but retain the same basic chemical structure as a natural amino acid. Amino acid mimetics refer to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but functions in a similar way to a natural amino acid. The term "antibody" as used herein refers to an immunoglobulin molecule that specifically binds to an antigen. In one aspect, the antigen is MCT1. The antibodies can be intact immunoglobulins derived from natural sources or from recombinant sources and can be immunoreactive portions of intact immunoglobulins. The term is used in the broadest sense and includes polyclonal and monoclonal antibodies, including intact antibodies and functional (antigen-binding) antibody fragments, including antigen-binding (Fab) fragments, F(ab) ')2, Fab' fragments, Fv fragments, recombinant IgG (rlgG) fragments, single chain antibody fragments including single chain variable (scFv) fragments, ByTE, multispecific antibody polypeptides, diabodies and single domain antibody fragments (eg, sdAb, sdFv, nanobody). The term encompasses engineered and / or otherwise modified forms of immunoglobulins, such as intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, multispecific, eg, bispecific, diabodies, triabodies, and tetrabodies, di-scFv and tri-scFv in tandem. Unless otherwise indicated, the term "antibody" is further understood to encompass functional antibody fragments thereof. The term also encompasses intact or full-length antibodies, including antibodies of any class or subclass, including IgG and its subclasses, IgM, IgE, IgA, and igD. The term "antigen-binding fragment" or "antibody fragment" refers to a portion of an intact antibody and refers to the antigen-determining variable regions of an intact antibody. Examples of antibody fragments include, but are not limited to, zncAan / nznz / q / Yi fragment antigen (Fab) binding fragments, F(ab')2 fragments, Fab' fragments, Fv fragments, recombinant IgG (rlgG) fragments ), single chain antibody fragments, including single chain variable fragments (scFv), single domain antibody fragments (eg, sdAb, sdFv, nanobody), diabodies, and multispecific antibodies formed from antibody fragments. Furthermore, despite the fact that the two domains of the Fv fragment, Vl and Vh, are encoded by different genes, they can be joined using recombinant methods, using a synthetic linker that allows them to be obtained as a single protein chain in in which the Vl and Vh regions pair to form monovalent molecules known as single-chain Fv (scFv). See, for example, Bird, et al. (1988) Science and 242: 423-426; Huston et al. (1988) Proc. nati. Acad. Sel. US 85: 5879-5883; and Osbourn et al. (1998) Nat. Biotechnology 16: 778. Such single chain antibodies are also intended to be encompassed by the term "antigen binding portion" of an antibody. Any specific scFv Vh and Vl sequence can be ligated to human immunoglobulin constant region cDNA or genomic sequences, to generate expression vectors encoding full-length IgG molecules or other isotypes. Vh and Vl can also be used in the generation of Fab, Fv or other immunoglobulin fragments through the use of protein chemistry or recombinant DNA technology. Other forms of single chain antibodies such as diabodies are also encompassed. Diabodies are bispecific bivalent antibodies in which the Vh and Vl domains are expressed on a single polypeptide chain but using a linker that is too short to allow pairing between the two domains on the same chain, so that the domains are forced to pair with complementary domains from another strand and two antigen-binding sites are created. See, for example, Holliger, et al. (1993) Proc. nati. Acad. Sci. USA 90: 64446448; Poljak et al. (1994) Structure 2: 1121-1123. Even further, an antibody, or antigen-binding portion thereof, (antigen-binding fragment, antibody fragment, antibody portion) can form part of larger immunoadhesion molecules, formed by covalent or noncovalent association of the antibody. or antibody portion with one or more proteins or peptides. Examples of immunoadhesion molecules include the use of the streptavidin core region to obtain a tetrameric scFv molecule (Kipriyanov, S.M. et al. (1995) Human Antibodies and Hybridomas 6:93-101) and the use of a cysteine, a marker peptide, and a C-terminal polyhistidine tag to obtain bivalent or biotinylated scFv molecules. Kipriyanov et al. (1994) Mol. Immunol 31: 1047-1058. Portions of antibodies, such as Fab and F(ab')2 fragments, can be prepared from whole antibodies using conventional techniques such as papain or pepsin digestion, respectively, of whole antibodies. In addition, antibodies, antibody portions, and immunoadhesion molecules can be obtained using standard recombinant DNA techniques, as described herein. Antibodies can be polyclonal, monoclonal, xenogeneic, allogeneic, syngeneic, or modified forms thereof, eg, humanized, chimeric, bispecific, or multispecific antibodies. An antibody heavy chain, as used herein, refers to the larger of the two types of polypeptide chains present in all antibody molecules in their native zncRan / nznz / q / Yi conformations. An antibody light chain, as used herein, refers to the smaller of the two types of polypeptide chains present in all antibody molecules in their natural conformations. Kappa and lambda light chains refer to the two main light chain isotypes of antibodies. By the term synthetic antibody, as used herein, is meant an antibody that is generated through the use of recombinant DNA technology, such as, for example, an antibody expressed by a bacteriophage as described herein. The term is also to be construed as meaning an antibody that has been generated by the synthesis of a DNA molecule encoding the antibody and that the DNA molecule expresses an antibody protein, or an amino acid sequence that specifies the antibody, where the sequence DNA or amino acid sequencing technology has been obtained using synthetic DNA or amino acid sequencing technology that is available and well known in the art. The term antigen or Ag refers to a molecule that elicits an immune response, for example, an autoantigen in the case of (humoral) autoimmunity, or an alloantigen in the case of transplantation, or an allergen in the case of an allergic condition. This immune response may involve the production of antibodies or the activation of specific immunologically competent cells, or both. The mid-level trade person will understand that any macromolecule, including virtually any protein or peptide, can serve as an antigen. Furthermore, the antigens can be derived from recombinant or genomic DNA. Any DNA, comprising a nucleotide sequence or a partial nucleotide sequence that encodes a protein that elicits an immune response, will be understood by a mid-level trade to encode an antigen as that term is used herein. Furthermore, a mid-level trade person will understand that an antigen need not be encoded solely by a full length nucleotide sequence of a gene. It is clear that the present invention includes, among others, the use of partial nucleotide sequences from more than one gene and that these nucleotide sequences are arranged in various combinations to encode polypeptides that elicit the desired immune response. Furthermore, a mid-level trade person will understand that an antigen need not be encoded by a gene at all. It is clear that an antigen can be generated, synthes...

Claims

1. An isolated antibody or antigen-binding fragment thereof that binds to one or more residues comprising an extracellular domain or region of human or non-human MCT1.

2. An isolated antibody or antigen-binding fragment thereof that binds to human or non-human MCT1 and antagonizes, inhibits or blocks one or more MCT1-related functions, e.g., in vitro and / or in vivo.

3. An isolated antibody or antigen-binding fragment that binds to a non-human MCT1, e.g. rodent MCT1 such as mouse or rat, that optionally antagonizes, inhibits or blocks one or more MCT1-related functions, e.g. in vitro and / or in vivo.

4. The isolated antibody or antigen-binding fragment according to claim 3, further binding to human MCT1.

5. An isolated anti-MCT1 antibody or an antigen-binding fragment thereof that competes for binding to a human or non-human MCT1 such as any of the human MCT1 Ab1-Ab95 antibodies.

6. An isolated anti-MCT1 antibody or antigen-binding fragment thereof that binds to the MCT1 or to the overlapping epitope on human MCT1 such as any of the human anti-MCT1 antibodies Ab1-Ab95.

7. An isolated anti-MCT1 antibody or antigen-binding fragment thereof that binds to an epitope on human MCT1 selected from the following: (i) one comprising one or more of the residues T41, E46, S285, S286, Y287, K289, H292, Y293, K297, G417, I47 and D418; (ii) one comprising at least three residues wherein at least one, two or all three of said residues comprise a residue selected from T41, E46, S285, S286, Y287, K289, H292, Y293, G417, I47 and D418; (iii) one comprising three residues wherein at least one, two, or all three of said residues comprise T41, E46, S285, S286, Y287, K289, H292, Y293, G417, I47, and D418; (iv) one comprising three to six residues wherein one, two, three, four, five, or six of said residues comprise T41, E46, S285, S286, Y287, K289, H292, Y293, G417, I47, and D418; (v) one comprising at least one, two, or all three residues T41, S285, and S286; (vi) one comprising T41; (vii) one comprising S286;(viii) one comprising S285; (ix) one comprising H292; (x) one comprising residues T41, S285, S286, Y287, G417 and D418; (xi) one comprising residues T41, S285 and S286; (xii) one comprising residues T41, I47, S285, S286, G417 and D418, zncRan / nznz / q / Yi 217 (xiii) one comprising residues E46, K289 and H292; (xiv) one comprising residues K297, Y293 and H292; (xv) one comprising one or more of the residues corresponding to a non-human MCT1, for example, selected from rodent (for example, mouse, rat, guinea pig), rabbit, chicken, non-human primate (for example, Macaca fascicularis, chimpanzee, orangutan), bovine, ovine, canine and feline; wherein optionally the residues present in said epitope are identified by the use of alanine scanning.

8. An isolated anti-MCT1 antibody or antigen-binding fragment thereof that binds to an epitope on human MCT1 selected according to claim 7, wherein said antibody or antigen-binding fragment further interacts with one or more of the following residues: (i) one or more of residues P37, I40, K45, E48 and T55 (loop 1); (ii) residue Q111 (loop 2); (iii) residue Q166 (loop 3); (iv) one or more of residues L284, E296, S298 (loop 4); (v) residue Y353 (loop 5); (vi) one or both residues Y419, T422 (loop 6); and / or (vii) any combination of the foregoing.

9. An isolated anti-MCT1 antibody or antigen-binding fragment thereof that binds to an epitope on non-human MCT1, wherein said non-human MCT1 is optionally selected from rodent (e.g. mouse, rat, guinea pig), rabbit, bird (e.g. chicken, turkey, goose), non-human primates (e.g. Macaca fascicularis, chimpanzee, orangutan), bovine, ovine, canine, feline, wherein optionally said epitope on non-human MCT1 comprises one or more of the corresponding residues on the non-human MCT1 such as one or more of T41, S285, S286, Y287, G417, I47 and D418 of human MCT1.

10. The isolated anti-MCT1 antibody or antigen-binding fragment thereof according to claim 8 or 9 that antagonizes, inhibits or blocks one or more of the activities of said non-human MCT1, e.g., in vitro and / or in vivo.

11. The isolated anti-MCT1 antibody or antigen-binding fragment thereof according to any of the preceding claims, which is human, humanized, non-human primate, primatized, chicken, rodent, or chimeric.

12. The isolated anti-MCT1 antibody or antigen-binding fragment thereof according to any of the preceding claims, which inhibits human MCT1-mediated lactate transport, e.g., in vitro and / or in vivo.

13. The isolated anti-MCT1 antibody or the antigen-binding fragment thereof according to any of the preceding claims, which binds to endogenous MCT1-expressing cells and / or binds to recombinant or genetically engineered MCT1-expressing cells, e.g., human MCT1-expressing cells.

14. An isolated anti-MCT1 antibody or an antigen-binding fragment thereof according to any of the preceding claims, wherein the antibody or antigen-binding fragment thereof is selected from the group consisting of: a human or humanized monoclonal antibody; a monospecific antibody; a polyspecific antibody; a multispecific antibody-type polypeptide; a humanized antibody; a human or humanized tetrameric antibody; a human or humanized tetravalent antibody; a human or humanized multispecific antibody; a single-stranded antibody; a domain-specific antibody; a single-domain antibody; a deleted domain antibody; an scFc fusion protein; a chimeric antibody; a synthetic antibody; a recombinant antibody; a hybrid antibody; a multispecific antibody; a bispecific antibody; a ByTE; a mutated antibody; CDR-grafted antibodies; an antibody fragment; a Fab;an F(ab')2; a Fab' fragment; an Fv fragment; a single-stranded Fv fragment (scFv); an Fd fragment; a dAb fragment; diabodies; a nanobody; a bivalent nanobody; a VHH antibody; and a minibody.

15. The isolated anti-MCT1 antibody or antigen-binding fragment thereof according to any of the preceding claims, which is a humanized antibody or antigen-binding fragment thereof.

16. The isolated anti-MCT1 antibody or antigen-binding fragment thereof according to any of the preceding claims comprising at least 1, 2, 3, 4, 5 or all 6 CDRs of any of the anti-MCT1 antibodies Ab1-Ab95, wherein optionally said CDRs are defined according to Kabat or according to Chothia and Lesk, or an isolated antibody or antigen-binding fragment thereof that competes for binding to MCT1 or that binds to this epitope with any of the anti-MCT1 antibodies Ab1-Ab95 or an affinity-matured variant of any of the foregoing.

17. A humanized anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims, comprising the same CDRs as any of the anti-MCT1 antibodies Ab1-Ab95, wherein optionally said CDRs are defined according to Kabat or according to Chothia and Lesk.

18. An anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims, comprising the same Vh polypeptide that is comprised in an anti-MCT1 antibody selected from Ab1-Ab95 or a humanized variant thereof.

19. An anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims, comprising the same polypeptide V1 that is comprised in an anti-MCT1 antibody selected from Ab1-Ab95 or a humanized variant thereof.

20. An anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims, comprising a polypeptide Vh and a polypeptide Vl that are identical to those comprising an anti-MCT1 antibody selected from Ab1-Ab95 or a humanized variant thereof. zncRan / nznz / q / Yi 219 21. The anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims, comprising a variable heavy polypeptide and / or a variable light chain polypeptide having respectively at least 80, 90, 95, 96, 97, 98, 99 or 100% sequence identity with a variable heavy polypeptide and / or a variable light chain polypeptide contained in any of the anti-MCT1 antibodies Ab1-Ab95.

22. An anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims, comprising polypeptides Vh CDR1,2 and 3 respectively having the amino acid sequences of SEQ ID NO: 4-6 and polypeptides Vl CDR1, 2 and 3 respectively having the amino acid sequences of SEQ ID NO: 7-9.

23. A humanized anti-MCT1 antibody or antigen-binding fragment derived from any of Ab1-Ab95, optionally containing the same CDRs as any of Ab1-Ab95, wherein such CDRs are optionally defined according to Kabat or according to Chothia and Lesk.

24. An affinity-matured anti-MCT1 antibody or antigen-binding fragment derived from any of Ab1-Ab95, wherein at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 CDR residues are mutated relative to the CDR residues comprising the 6 CDR polypeptides of any one of Ab1-Ab95, wherein optionally said affinity-matured anti-MCT1 antibody binds to human MCT1 with at least the same or greater affinity than the anti-MCT1 antibody from which it is derived and / or the antigen-binding fragment or affinity-matured antibody antagonizes human MCT1, for example, in vitro and / or in vivo, wherein optionally said CDRs are defined according to Kabat or according to Chothia and Lesk.

25. An affinity-matured anti-MCT1 antibody or antigen-binding fragment or an antigen-binding fragment according to claim 24 wherein, at most, 1, 2, 3, 4, 5, 6 or 7 CDR residues are mutated relative to the CDR polypeptides of any of Ab1-Ab95.

26. An affinity-matured anti-MCT1 antibody or antigen-binding fragment or the antigen-binding fragment according to claim 24 wherein, at most, 1, 2, 3 or 4 CDR residues are mutated relative to the CDR polypeptides of any of Ab1Ab95.

27. An affinity-matured anti-MCT1 antibody or antigen-binding fragment or an antigen-binding fragment according to claim 24 wherein, at most, 1 or 2 CDR residues are mutated relative to the CDR polypeptides of either Ab1Ab95.

28. A human anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims, further bound to a non-human MCT1, optionally a non-human rodent, rabbit, chicken, or primate MCT1.

29. An anti-MCT1 antibody comprising the Vh and Vl polypeptides of SEQ ID NO: 2 and 3; SEQ zncAan / nznz / q / Yi 220 ID NO: 12 and 13; SEQ ID NO: 14 and 15; SEQ ID NO: 16 and 17; or one comprising the Vl and / or Vh polypeptides of any of the Ab5-Ab95 antibodies, or comprising humanized or affinity-matured variants of the Vl and / or Vh polypeptides of any of the Ab5-Ab95 antibodies.

30. An anti-MCT1 antibody or antigen-binding fragment comprising a variable heavy-chain polypeptide or a heavy-chain polypeptide having an amino acid sequence selected from SEQ ID NO: 2, 12, 14, 16, 19-32, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153 and 155: and a variable light chain polypeptide or light chain polypeptide having an amino acid sequence selected from SEQ ID NO: 3, 13, 15, 17, 33-44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154 and 156.

31. An anti-MCT1 antibody or antigen-binding fragment comprising a variable heavy-chain polypeptide and a variable light-chain polypeptide having an amino acid sequence selected respectively from the following: SEQ ID NO: 2 and 3; SEQ ID NO: 12 and 13; SEQ ID NO: 14 and 15; SEQ ID NO: 16 and 17; SEQ ID NO: 45 and 46; SEQ ID NO: 47 and 48; SEQ ID NO: 49 and 50; SEQ ID NO: 51 and 52; SEQ ID NO: 53 and 54; SEQ ID NO: 55 and 56; SEQ ID NO: 57 and 58; SEQ ID NO: 59 and 60; SEQ ID NO: 61 and 62; SEQ ID NO: 63 and 64; SEQ ID NO: 65 and 66; SEQ ID NO: 67 and 68; SEQ ID NO: 69 and 70; SEQ ID NO: 71 and 72; SEQ ID NO: 73 and 74; SEQ ID NO: 75 and 76; SEQ ID NO: 77 and 78; SEQ ID NO: 79 and 80; SEQ ID NO: 81 and 82; SEQ ID NO: 83 and 84; SEQ ID NO: 85 and 86; SEQ ID NO: 87 and 88; SEQ ID NO: 89 and 90; SEQ ID NO: 91 and 92; SEQ ID NO: 93 and 94; SEQ ID NO: 95 and £ SEQ ID NO: 103 and 104 SEQ ID NO: 111 and 112 SEQ ID NO: 119 and 120 SEQ ID NO: 127 and 128 SEQ ID NO: 135 and 136 SEQ ID NO: 143 and 144 SEQ ID NO: 151 and 152; 6;SEQ ID NO: 97 and 98; SEQ ID NO: 105 and 106; SEQ ID NO: 113 and 114; SEQ ID NO: 121 and 122; SEQ ID NO: 129 and 130; SEQ ID NO: 137 and 138; SEQ ID NO: 145 and 146; SEQ ID NO: 153 and 154 and SEQ ID NO: 99 and 100; SEQ ID NO: 107 and 108 SEQ ID NO: 115 and 116 SEQ ID NO: 123 and 124 SEQ ID NO: 131 and 132 SEQ ID NO: 139 and 140 SEQ ID NO: 147 and 148 SEQ ID NO: 155 and 156. SEQ ID NO: 101 and 102; SEQ ID NO: 109 and 110; SEQ ID NO: 117 and 118; SEQ ID NO: 125 and 126; SEQ ID NO: 133 and 134; SEQ ID NO: 141 and 142; SEQ ID NO: 149 and 150; 32. A humanized anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims comprising a polypeptide V1 having an amino acid sequence selected from those of SEQ ID NO: 3, 13, 15, 17 and 33-44 or that of any of the antibodies Ab5-Ab60.

33. A humanized anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims comprising a Vh polypeptide having an amino acid sequence selected from those of SEQ ID NO: 2, 12, 14, 16 and 19-32 or that of any of the Ab5-Ab60 antibodies. 221 34. A humanized anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims comprising a polypeptide Vl having an amino acid sequence selected from SEQ ID NO: 13, 15, 17 and 33-44 and a polypeptide Vh having an amino acid sequence selected from those of SEQ ID NO: 12, 14, 16 and 19-32 or that of any of the antibodies Ab5-Ab60.

35. A humanized anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims comprising a polypeptide V1 having a sequence having at least 80, 85, 90, 95, 96, 97, 98 or 99% sequence identity to any of SEQ ID NO: 3, 13, 15, 17, 33-44 or to a polypeptide V1 comprising any of the antibodies Ab5-Ab95.

36. A humanized anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims comprising a Vh polypeptide having a sequence having at least 80, 85, 90, 95, 96, 97, 98, 99% or 100% sequence identity with any of SEQ ID NO: 2, 12, 14, 16, 19-32 or with a Vh polypeptide comprising any of the Ab5-Ab95 antibodies.

37. A humanized anti-MCT1 antibody or antigen-binding fragment according to any of the foregoing comprising a polypeptide Vl having a sequence possessing at least 80, 85, 90, 95, 96, 97, 98 or 99% sequence identity to any of SEQ ID NO: 3, 13, 15, 17, 33-44 or to a polypeptide Vl comprising any of the Ab5-Ab95 antibodies and / or a polypeptide Vh having a sequence having at least 90, 95, 96, 97, 98, 99% or 100% sequence identity to the polypeptide Vh of SEQ ID NO: 2, 12, 14, 16, 19-32 or to a polypeptide Vh comprising any of the Ab5-Ab95 antibodies.

38. The humanized anti-MCT1 antibody or an antigen-binding fragment according to any of the preceding claims, wherein the heavy chain CDR3 sequence comprises 18, 19, 20, 21, 22, 23 or 24 amino acid residues.

39. The humanized anti-MCT1 antibody or an antigen-binding fragment according to any of the preceding claims, wherein the heavy chain CDR3 sequence comprises 21, 22, 23 or 24 amino acid residues.

40. The human anti-MCT1 or antigen-binding fragment isolated according to any of the preceding claims, wherein the heavy chain CDR3 sequence is identical to SEQ ID NO: 6 or differs from it by a maximum of 5, 4, 3, 2 or 1 residues, optionally wherein such differences, if present, comprise conservative amino acid substitutions or comprise substituent amino acids that are prevalent in the same position in the heavy chain CDR3 of human or rodent antibodies comprising a CDR3 of the same length.

41. The isolated human or humanized anti-MCT1 antibody or an antigen-binding fragment thereof according to any of the preceding claims competing for binding to MCT1 with a reference antibody, wherein the reference antibody is selected from Ab1- zncRan / nznz / q / Yi 222 Ab95.

42. A human anti-MCT1 antibody or antigen-binding fragment thereof comprising the same CDRs as any of Ab1-Ab95 and / or comprising the same variable heavy and / or light CDR polypeptides as a human anti-MCT1 antibody selected from Ab1-Ab95.

43. An anti-MCT1 antibody comprising the variable heavy and / or light polypeptides of an antibody selected from Ab1-Ab95.

44. A human or humanized anti-MCT1 antibody or an antigen-binding fragment thereof according to any of the preceding claims, comprising heavy and / or light chain constant regions, optionally heavy and / or light chain constant regions of human lgG1, lgG2, lgG3 or lgG4 whose constant regions are optionally mutated to impair or enhance at least one effector function.

45. The anti-MCT1 antibody according to claim 44, wherein said effector functions include FcR binding, complement binding, ADCC function, FcRN binding, and glycosylation.

46. ​​An anti-MCT1 antibody or antigen-binding fragment thereof according to any of the preceding claims, wherein the CDRs of the antibody or antigen-binding fragment thereof form a three-dimensional antibody structure similar to or the same as that of Ab1, as indicated by the positions of the alpha carbons in the corresponding CDRs differing by a root mean square deviation (RMSD) of less than 2.0 Å, less than 1.0 Å, or less than 0.5 Å, as determined by structural alignment.

47. A humanized antibody or antigen-binding fragment thereof comprising the Ab1 variable heavy chain CDR sequences (SEQ ID NOS: 4, 5, 6) and the Ab1 variable light chain CDR sequences (SEQ ID NOS: 7, 8, 9).

48. An anti-MCT1 antibody or antigen-binding fragment thereof comprising a Vh domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity with the amino acid sequence of the Vh domain of MCT1 Ab1 (SEQ ID NO: 2); and comprising a Vl domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity with the amino acid sequence of the Vl domain of MCT1 Ab1 (SEQ ID NO: 3).

49. An anti-MCT1 antibody or antigen-binding fragment thereof according to any of the preceding claims comprising human constant domains, optionally lgG1, lgG2, lgG3 or lgG4, further optionally modified to enhance at least one Fe effector function selected from glycosylation, FcR binding, FcRN binding, complement binding and ADCC function.

50. An anti-MCT1 antibody or antigen-binding fragment thereof according to any of the preceding claims comprising human lgG1 constant regions, optionally modified to decrease FcR binding and / or complement binding, which zncRan / nznz / q / YiAi 223 further comprises optionally E269R and / or K322A mutations and / or said human lgG1 constant regions comprise the amino acid sequence SEQ ID NO:

18.

51. A fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide, or multispecific or bispecific antibody polypeptide comprising at least one anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims.

52. The anti-MCT1 antibody, fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide, or multispecific or bispecific antibody polypeptide according to any of the preceding claims, which decreases the activity of effector T lymphocytes and / or the number of effector T lymphocytes, for example, CD3+, CD4+, or CD8+ effector T lymphocytes.

53. The anti-MCT1 antibody, fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide, or multispecific or bispecific antibody polypeptide according to any of the preceding claims that increases the activity and / or number of Tr1 lymphocytes.

54. The anti-MCT1 antibody, fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide, or multispecific or bispecific antibody polypeptide according to any of the preceding claims, which decreases the activity of effector T lymphocytes and / or the number of effector T lymphocytes, for example, CD3+, CD4+, or CD8+ effector T lymphocytes, and further increases the activity and / or number of Tr1 lymphocytes.

55. A cell expressing at least one anti-MCT1 antibody or antigen-binding fragment, a fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide, or multispecific or bispecific antibody polypeptide according to any of the preceding claims.

56. The cell according to claim 55 comprising a human, non-human mammalian, yeast, bacterial, amphibian, plant, insect or reptile cell.

57. The cell according to claim 55 comprising a human cell, optionally a human immune cell, for example a T lymphocyte, NK cell, monocyte, regulatory T lymphocyte or macrophage.

58. An anti-idiotypic antibody produced against an anti-MCT1 antibody or antigen-binding fragment thereof according to any of the preceding claims, which is optionally human, humanized and / or affinity matured.

59. An anti-idiotypic antibody produced against an anti-idiotypic antibody according to claim 58, which binds to MCT1.

60. The anti-idiotypic antibody according to claim 59 that blocks or antagonizes one or more MCT1 activities.

61. A fusion protein comprising an anti-MCT1 antibody or an antigen-binding fragment thereof according to any of the preceding claims or the polypeptide Vh zncAan / nznz / q / Yi 224 CDR3 of SEQ ID NO: 6 or a variant having at least 80% sequence identity with it, which is directly or indirectly linked to another polypeptide, for example, an antibody polypeptide or antibody domain, serum albumin, human or other primate serum albumin, adnectin, an affibody, a DARPin, an anticalin, glycol (PEG), monomethoxy PEG (mPEG), an XTEN molecule, an rPEG molecule or a fragment or variant of any of the foregoing.

62. The fusion protein according to claim 61 wherein the polypeptide or antibody domain comprises an Fe polypeptide or fragment thereof, for example, an Fe region of human lgG1, lgG2, lgG3 or lgG4 or fragment thereof.

63. An anti-MCT1 antibody or antigen-binding fragment thereof or a fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide according to any of the preceding claims, or a cell expressing any of the foregoing according to any of the preceding claims, which confers one or more of the following properties upon binding to MCT1 on the surface of a cell, for example, an activated T lymphocyte or B lymphocyte, and optionally a human cell: (i) inhibits lactate transport; (ii) inhibits bromopyruvate transport; (iii) inhibits the transport of one or more monocarboxylates, pyruvate, branched-chain oxoacids derived from leucine, valine and isoleucine, ketone bodies, acetoacetate, beta-hydroxybutyrate, acetate, lactic acid, cellular nutrients, metabolites, ions, hormones, lipids, and ketones;(iv) inhibits the proliferation of CD3 / CD28-stimulated T lymphocytes; (v) inhibits the proliferation of activated T or B lymphocytes; (vi) inhibits the production of one or more inflammatory cytokines; (vii) decreases the activity and / or number of effector T lymphocytes, e.g., CD3+, CD4+ and / or CD8+ effector T lymphocytes; (viii) increases the proportion or activity of regulatory T lymphocytes (Tregs); (ix) inhibits allogeneic activation in a mixed lymphocyte reaction; (x) or a combination of any of the above.

64. The anti-MCT1 antibody or antigen-binding fragment thereof or a fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide according to any of the preceding claims, or a cell expressing any of the foregoing, for example, according to any of the preceding claims, inhibiting the production of one or more inflammatory cytokines by binding to MCT1.

65. An anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide, or multispecific or bispecific antibody polypeptide according to any of the preceding claims, or a cell expressing any of the foregoing according to claim 64, wherein at least one of the one or more inflammatory cytokines is selected from FGF2, FLT-3L, Fractalkine, G-CSF, GM-CSF, GRO, IFNa2, IFNγ, IL-3, IL-5, IL-9, IL-10, IL-12p40, IL-12p70, IL-13, IL-17α, IP-10, MCP-1, MDC, MIP-1α, MIP-1β, SCD40β, TNFα, and TNRP.

66. An anti-MCT1 antibody or an antigen-binding fragment thereof or a fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide according to any of the preceding claims, or a cell expressing any of the foregoing according to claim 64 or 65, wherein at least one of the one or more inflammatory cytokines is selected from IFNγ, GM-CSF, TNFα, IL-10 and IL-6.

67. An anti-MCT1 antibody or antigen-binding fragment thereof or a fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide according to any of the preceding claims, or a cell expressing any of the foregoing, inhibiting MCT1-mediated lactate transport in activated T lymphocytes with a Kd of less than 100 nM, less than 50 nM or less than 10 nM, as measured by a lactate FLIPR assay.

68. An anti-MCT1 antibody or antigen-binding fragment thereof or a fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide according to any of the preceding claims, or a cell expressing any of the foregoing, which does not: (i) bind to MCT2, MCT3, MCT4 and / or CD147 as measured by flow cytometry; (ii) inhibit the transport of MCT2, MCT3 and / or MCT4; (iii) inhibit the production of IL-2; (iv) inhibit lactate transport in monocytes; (v) inhibit the proliferation of untreated, resting and / or regulatory T lymphocytes; (vi) inhibit lactate transport in RBCs; (vil) alters the expression of one or more T-cell activation markers, optionally selected from CD25, CD54, CD69, CD95, CD98, CD147, CD154, CD278, CD279 and HLA-DR / DP / DQ.

69. An anti-MCT1 antibody or antigen-binding fragment thereof, or a fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide, or multispecific or bispecific antibody polypeptide according to any of the preceding claims, or a cell expressing any of the foregoing, comprising an Fe region of human IgG1, IgG2, IgG3, or IgG4, optionally an Fe region modified to alter at least one of the effector functions, half-life, proteolysis, or glycosylation, wherein the Fe region optionally contains one or more mutations that alter or eliminate N- and / or O-glycosylation. zncAan / nznz / q / Yi 226 70. An anti-MCT1 antibody or antigen-binding fragment thereof or a fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide according to any of the preceding claims, or a cell expressing any of the foregoing, binding to human MCT1 with an affinity (KD) of less than 100 nM, less than 50 nM or less than 10 nM.

71. An anti-MCT1 antibody or antigen-binding fragment thereof or a fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide according to any of the preceding claims, or a cell expressing any of the preceding claims, further having one or more of the following modifications: (i) conjugated to a cytotoxic agent; (ii) comprised in a bispecific antibody; (iii) comprised in a multispecific antigen-binding protein; (iv) conjugated to a tag; and (v) conjugated to another therapeutic agent, optionally an immunosuppressant or a chemotherapeutic agent.

72. An anti-MCT1 antibody or antigen-binding fragment thereof or a fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide according to any of the preceding claims, or a cell expressing any of the foregoing, wherein the marker is a chemiluminescent marker, a paramagnetic marker, an MRI contrast agent, a fluorescent tag, a bioluminescent tag, or a radioactive tag or the cytotoxic agent is a portion that inhibits the synthesis of DNA, RNA or protein; a radionuclide; or a ribosomal inhibitory protein.

73. An anti-MCT1 antibody or antigen-binding fragment thereof or a fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide according to any of the preceding claims, or a cell expressing any of the foregoing, which is suitable for treating a human subject having an autoimmune, inflammatory, or allergic condition; metabolic disorder (e.g., diabetes), polycystic kidney disease (ADPKD), cancer; transplant recipient or HIE or any other condition in which decreased numbers and / or activity of effector T lymphocytes, e.g., CD3+ T lymphocytes, CD4+ T lymphocytes and / or CD8+ T lymphocytes and / or increased activity and / or numbers of suppressor T lymphocytes or Tr1 is therapeutically desirable.

74. An anti-idiotypic antibody or antigen-binding fragment thereof produced against an anti-MCT1 antibody or antigen-binding fragment thereof according to any of the preceding claims, optionally neutralizing one or more biological effects of the anti-MCT1 antibody or antigen-binding fragment thereof to which it binds. zncRan / nznz / q / Yi 227 75. An anti-idiotypic antibody or an antigen-binding fragment thereof produced against an anti-idiotypic antibody or antigen-binding fragment thereof according to claim 74, optionally wherein the anti-idiotypic antibody or antigen-binding fragment thereof neutralizes the anti-idiotypic antibody or antigen-binding fragment thereof to which it binds.

76. A method of using the anti-idiotypic antibody according to claim 74 to control the in vivo levels of said anti-MCT1 antibody or antigen-binding fragment thereof in a subject or to neutralize the in vivo effects of said anti-MCT1 antibody or antigen-binding fragment thereof in a subject.

77. A polynucleotide encoding the anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide or anti-antiMCT1 antibody or antigen-binding fragment or anti-anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims.

78. An expression vector comprising the polynucleotide according to claim 77.

79. A host cell comprising the polynucleotide according to claim 77 or the expression vector according to claim 78, optionally a human immune cell, for example a T lymphocyte, a B lymphocyte or an NK cell.

80. A pharmaceutical or diagnostic composition comprising an effective amount of anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide or anti-anti-MCT1 antibody or antigen-binding fragment or anti-anti-MCT1 antibody or antigen-binding fragment according to any of the preceding claims or a cell expressing any of the foregoing.

81. The pharmaceutical composition according to claim 80 that is suitable for use in human or non-human treatment or prophylaxis.

82. A method for producing an isolated anti-MCT1 antibody or an antigen-binding fragment thereof comprising culturing the host cell according to claim 79 under conditions allowing expression of the antibody or antigen-binding fragment thereof; and recovering the antibody or antigen-binding fragment thereof from the culture medium or host cell.

83. A pharmaceutical composition comprising a pharmaceutically effective amount of an isolated anti-MCT1 antibody or antigen-binding fragment thereof, anti-idiotypic antibody, fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide, or multispecific or bispecific antibody polypeptide, or a cell expressing any of the foregoing, according to any of the preceding claims. zncAan / nznz / q / Yi 228 84. The pharmaceutical composition according to claim 83, further comprising a pharmaceutical diluent, carrier or excipient.

85. The pharmaceutical composition according to claim 83 or 84, which includes another therapeutic agent.

86. The pharmaceutical composition according to claim 85, wherein said other therapeutic agent is a mitochondrial inhibitor and / or a biguanide and / or another monocarboxylate transporter (MCT inhibitor), for example, an SLC16A1, SLC16A2, SLC16A3, SLC16A4, SLC16A5, SLC16A6, SLC16A7, SLC16A8, SLC16A9, SLC16A10, SLC16A11, SLC16A12, SLC16A13 or SLC16A14 or an inhibitor of MCT1, MCT2, MCT3, MCT4, MCT5, MCT6, MCT7, MCT8, MCT9 or MCT10, wherein said inhibitor may inhibit one or more of the above transporters and further said inhibitor optionally comprises a small molecule, RNAi, antibody, antibody fragment or a fusion protein.

87. The pharmaceutical composition according to claim 85 or 86, wherein said other active agent is selected from metformin, phenformin, alexidine, bisbiguanide, buformin, chlorhexidine, chlorproguanil, phenylbiguanide, polyaminopropyl biguanide, polyhexanide, moroxidine, glipizide, glyburide, repaglinide, saxagliptin, sitagliptin, pyrvinium pamoate, proguanil, doxycycline, atovaquone, canagliflozin, glitazones (for example, troglitazone, pioglitazone, rosiglitazone), tigecycline, thiazolides (for example, nitazoxanide), salicylanilides (for example, closantel, oxyclozanide, niclosamide), perhexiline, propronolol, fenofibrate, miconazole, nefazodone, pentamidine, hydrocortisone, metaiodobenzylguanidine, lonidamine, alpha tocopheryl succinate (primary form of vitamin E), carbonic anhydrase, ME344 (MEI Pharma), HIF1a inhibitors (e.g., chrysin, ketomin, dimethicone bisphenol A, BAY84-2243), SR13800, dimethyloxaloylglycine (DMOG),p-Trifluoromethoxyphenylhydrazone carbonylcyanide (FCCP), m-chlorophenylhydrazone carbonylcyanide (CCCP), antimycin A, oligomycin, salinomycin, dinitrophenol, rotenone, phenformin, tirfostine 9, aptene A5, berberine, azide, cyanide, nitrous oxide, arsenic trioxide, pyrvinium, canagliflozin, rosiglitazone, amobarbital, Honokol, arctigenin, caffeic acid phenyl ester, perphenazine, trifluorooperazine, methylglyoxal and combinations comprising any of the foregoing.

88. A method for inhibiting the activity and / or number of effector T lymphocytes, for example, CD3+, CD4+ and / or CD8+ effector T lymphocytes in a subject in need, comprising administering to the subject a therapeutically or prophylactically effective amount of an anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide according to any of the preceding claims or a cell expressing at least one of the foregoing or a pharmaceutical composition containing a therapeutically or prophylactically effective amount of any of the foregoing.

89. A method for increasing the activity and / or number of effector T lymphocytes, for example, suppressor T lymphocytes or Tr1 in a subject in need, comprising administering to the subject a therapeutic or prophylactically effective amount of an anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide according to any of the preceding claims or a cell expressing at least one of the foregoing or a pharmaceutical composition containing a therapeutic or prophylactically effective amount of any of the foregoing.

90. A method for inhibiting the activity and / or number of effector T lymphocytes, for example, CD3+, CD4+ and / or CD8+ effector T lymphocytes and increasing the activity and / or number of suppressor T lymphocytes or Tr1 in a subject in need, comprising administering to the subject a therapeutically or prophylactically effective amount of an anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide according to any of the preceding claims or a cell expressing at least one of the foregoing or a pharmaceutical composition containing a therapeutically or prophylactically effective amount of any of the foregoing.

91. The method according to claims 88-90, wherein the subject has an autoimmune, allergic, inflammatory, metabolic disorder, cancer, transplant recipient, cell therapy recipient, EIHI condition, polycystic kidney disease (ADPKD) characterized by increased effector T lymphocyte activity, e.g., CD3+, CD4+ or CD8+, and / or decreased suppressor T lymphocyte or Tr1 activity, and / or decreased number of suppressor T lymphocytes or Tr1.

92. A method for preventing or treating an autoimmune condition, an allergic condition, an inflammatory condition, a metabolic disorder, cancer, a transplant recipient, a cell therapy recipient, an HIE condition, polycystic kidney disease (ADPKD), or symptoms associated with any of these conditions, comprising administering to a subject in need a therapeutically or prophylactically effective amount of an anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide, or multispecific or bispecific antibody polypeptide according to any of the preceding claims, or a cell expressing at least one of the foregoing, or a pharmaceutical composition containing a therapeutically or prophylactically effective amount of any of the foregoing.

93. The method according to claim 92, wherein the subject has an autoimmune, allergic, inflammatory, metabolic disorder, cancer, transplant recipient, cell therapy recipient, EIHI condition, polycystic kidney disease (ADPKD) characterized by increased effector T lymphocyte activity, e.g., CD3+, CD4+ or CD8+ and / or decreased suppressor T lymphocyte or Tr1 activity and / or decreased number of suppressor T lymphocytes or Tr1.

94. The method according to claim 92, 93 or 94, wherein the metabolic disorder zncAan / nznz / q / Yi 230 comprises Danon disease, diabetes mellitus, Duarte galactosemia, MDP syndrome, metabolic myopathy, methylenetetrahydrofolate reductase deficiency, Winchester syndrome, salicylate sensitivity, X-linked hypophosphatemia, alcoholic ketoacidosis, allergic reaction to alcohol, alpha-aminoadipic and alpha-ketoadipic aciduria, high anion gap metabolic acidosis, gout, refeeding syndrome, exercise-associated hyponatremia, pancreatitis, pansteatitis and Metab-L.

95. The method according to claims 88-94, wherein the condition is mediated, at least in part, by activated T lymphocytes or B lymphocytes and / or cells expressing MCT1.

96. The method according to any one of claims 88-95, wherein administration of the antibody or antigen-binding fragment thereof or fusion protein has one or more of the following effects: (i) inhibits lactate transport in activated T lymphocytes or B lymphocytes; (ii) inhibits bromopyruvate toxin transport in activated T lymphocytes or B lymphocytes; (iii) inhibits the proliferation of CD3 / CD28-stimulated T lymphocytes; (iv) inhibits the proliferation of activated T lymphocytes; (v) inhibits the production and / or secretion of one or more inflammatory cytokines; (vi) does not inhibit the production and / or secretion of IL-2; (vii) increases the production of ketones in urine; (viii) increases survival time; (ix) decreases graft rejection; (x) increases the proportion or activity of regulatory T lymphocytes (Tregs); (xi) increases the proportion of CD4+ T lymphocytes that are Tregs; (xii) decreases the proportion of IgG1+ B lymphocytes;(xiii) decreases the proportion of germinal center B lymphocytes; (xiv) does not inhibit lactate transport in human RBCs; (xv) decreases T lymphocyte activation; and (xvi) decreases cytotoxic T lymphocyte activity.

97. The method according to any of claims 88-96, which is used to treat or prevent at least one of lupus, graft rejection, graft-versus-host disease (GVHD), type 1 or 2 diabetes, or obesity.

98. The method according to any of claims 88-97, wherein the efficacy of the treatment is monitored by measuring ketones in urine, an increase in the number of TR1 lymphocytes, a reduced or increased expression of a selected biomarker of an inflammatory cytokine, IFNy, GM-CSF, TNFa, IL-10, IL-6, IL-2, TIGIT, PD1, granzyme B, by a decrease in the number of effector T lymphocytes and / or hCD3+ cells, suppression of PMBC proliferation, or a combination of any of the foregoing.

99. A method for evaluating the therapeutic efficacy of an anti-MCT1 antagonist antibody comprising detecting its effect in vitro or in vivo on any of the above: ketones in urine, the number of TR1 lymphocytes, the expression of a selected biomarker of an inflammatory cytokine, IFNy, GM-CSF, TNFa, IL-10, IL-6, IL-2, TIGIT, PD1, granzyme B, a decrease in the number of effector T lymphocytes and / or hCD3+ cells, suppression of PMBC proliferation, or a combination of any of the above.

100. A method for treating or preventing cancer recurrence, comprising administering to a subject in need a therapeutically or prophylactically effective amount of an anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide according to any of the preceding claims or a cell expressing at least one of the foregoing or a pharmaceutical composition containing a therapeutically or prophylactically effective amount of any of the foregoing.

101. The method according to claim 100, wherein the tumor cells express MCT1.

102. The method according to any of claims 88-101, wherein the subject is a mammal.

103. The method according to claim 102, wherein the mammal is a human being, a non-human primate, or a rodent.

104. A method for inhibiting or reducing the activity of activated T lymphocytes or B lymphocytes, comprising contacting said activated cells with an anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide or a cell expressing at least one of the foregoing according to any of the preceding claims.

105. The method according to any of claims 88-104, wherein the anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide or a cell expressing at least one of the foregoing according to any of the preceding claims is administered as monotherapy.

106. The method according to any of claims 88-105, wherein the anti-MCT1 antibody or antigen-binding fragment thereof or fusion polypeptide, chimeric antigen receptor (CAR), multispecific antigen-binding polypeptide or multispecific or bispecific antibody polypeptide or a cell expressing at least one of the foregoing according to any of the preceding claims is administered in combination with a second therapeutic agent.

107. The method according to claim 106, wherein the therapeutic agent is selected from an immunosuppressant drug, a chemotherapeutic agent, a biguanide, for example, metformin or another antidiabetic agent, or an anti-inflammatory agent.

108. The method according to claim 106, wherein said other therapeutic agent is a mitochondrial inhibitor and / or a biguanide. zncRan / nznz / q / Yi 232 109. The method according to any one of claims 106-108, wherein said other therapeutic agent is selected from metformin, phenformin, alexidine, bisbiguanide, buformin, chlorhexidine, chlorproguanil, phenylbiguanide, polyaminopropyl biguanide, polyhexanide, moroxidine, glipizide, glyburide, repaglinide, saxagliptin, sitagliptin, pyrvinium pamoate, proguanil, doxycycline, atovaquone, canagliflozin, glitazones (e.g., troglitazone, pioglitazone, rosiglitazone), tigecycline, thiazolides (e.g., nitazoxanide), salicylanilides (e.g., closantel, oxyclozanide, niclosamide), perhexiline, propronolol, fenofibrate, miconazole, nefazodone, pentamidine, hydrocortisone, metaiodobenzylguanidine, lonidamine, alpha tocopheryl succinate (primary form of vitamin E), carbonic anhydrase, ME344 (MEI Pharma), HIF1a inhibitors (e.g., chrysin, ketomin, dimethicone bisphenol A, BAY84-2243), SR13800, dimethyloxaloylglycine (DMOG),p-Trifluoromethoxyphenylhydrazone carbonylcyanide (FCCP), m-chlorophenylhydrazone carbonylcyanide (CCCP), antimycin A, oligomycin, salinomycin, dinitrophenol, rotenone, phenformin, tirfostine 9, aptene A5, berberine, azide, cyanide, nitrous oxide, arsenic trioxide, pyrvinium, canagliflozin, rosiglitazone, amobarbital, Honokol, arctigenin, caffeic acid phenyl ester, perphenazine, trifluorooperazine, methylglyoxal and combinations comprising any of the foregoing.

110. The method according to any of claims 88-109, wherein the antibody, the antigen-binding fragment thereof, the fusion protein, or the pharmaceutical composition is administered enterally, parenterally, or topically.

111. A method for monitoring the effectiveness of treatment with an antibody or antigen-binding fragment thereof or fusion protein that binds to MCT1 and reduces MCT1-mediated lactate transport comprising measuring the level of ketones in urine.

112. A method for diagnosing a selected condition from an autoimmune, inflammatory, or allergic condition; a cancer; HIE; polycystic kidney disease (ADPKD); diabetes or another metabolic disorder, and / or a condition associated with the upregulation of MCT1, wherein said method comprises: (i) isolating the cells responsible for mediating the condition; (ii) contacting said cells with an anti-MCT1 antibody or antigen-binding fragment thereof or MCT1-binding fusion protein; and (iii) detecting the level of anti-MCT1 antibody or antigen-binding fragment or MCT1-binding fusion protein thereof bound to said cells.

113. The method according to claim 111 or 112, wherein the condition is an autoimmune, inflammatory, transplant, GVHD, metabolic (e.g. diabetes), HIE; polycystic kidney disease (PKD); or allergic condition.

114. The method according to claim 112, wherein the condition is an autoimmune, inflammatory, transplant, GVHD, metabolic (e.g., diabetes), polycystic kidney disease (ADPKD), or allergic condition, and the cells are activated T lymphocytes or B lymphocytes. zncAan / nznz / q / Yi 233 115. The method according to claim 112, wherein the condition is cancer and the cells are tumor cells.

116. The method according to claim 112, wherein the condition is EIHI and the cells are tumor cells.

117. The method according to any of claims 88-116, wherein the anti-MCT1 antibody or antigen-binding fragment thereof or MCT1-binding fusion protein comprises one or more of the following: (i) competes with an anti-MCT1 antibody selected from either Ab1-Ab95 or another anti-MCT1 antibody comprising the same CDRs as any of the foregoing anti-MCT1 antibodies; (ii) comprises the same CDRs as a human anti-MCT1 antibody selected from Ab1-Ab95; (iii) comprises an affinity-matured or humanized variant of a human anti-MCT1 antibody selected from Ab1-Ab95; (iv) competes with an antibody comprising a Vh domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity with the amino acid sequence of the Vh domain of MCT1 Ab1 (SEQ ID NO: 2) or with any Ab1-Ab59;and comprising a Vl domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% identity with the amino acid sequence of the Vl domain of MCT1 Ab1 (SEQ ID NO: 3) or with any of Ab2-Ab95; (v) comprising the heavy chain CDR sequences of MCT1 Ab1 (SEQ ID NOS: 4, 5, 6) and the light chain CDR sequences of MCT1 Ab1 (SEQ ID NOS: 7, 8, 9) or those of any of Ab2-Ab95; (vi) competes with an antibody comprising, or itself comprising, a Vh domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity with the amino acid sequence of the Vh domain of MCT1 Ab1 (SEQ ID NO: 2) or with any Ab2-Ab60; and comprising a Vl domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% identity with the amino acid sequence of the Vl domain of MCT1 Ab1 (SEQ ID NO: 3) or with any of Ab2-Ab60;(vii) competes with an antibody comprising, or co-compounding itself with, a Vn domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% identity with the amino acid sequence of the Vh domain selected from those of SEQ ID NO: 2, 12, 14, 16, 19-32 or with any of Ab5-Ab60; and / or (viii) competes with an antibody comprising, or itself composed of, a VL domain having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, to zncAan / nznz / q / Yi 234 less 99% or 100% identity with the amino acid sequence of the Vh domain selected from those of SEQ ID NO: 13, 15, 17 or 33-44 or with any of Ab5-Ab60;and / or (ix) comprises at least one peptide comprising a sequence identical to SEQ ID NO: 6 or comprising a sequence differing from it by at most 5, 4, 3, 2 or 1 residues, wherein said peptide is linked directly or indirectly to another polypeptide, for example, an antibody polypeptide or antibody domain, serum albumin, human or other primate serum albumin, adnectin, an affibody, a DARPin, an anticalin, glycol (PEG), monomethoxy PEG (mPEG), an XTEN molecule, an rPEG molecule or fragment or a variant of any of the foregoing.; 118. A method for detecting the expression of MCT1, optionally functional MCT1, by means of a cell comprising determining whether any of the anti-MCT1 antibodies according to any of the preceding claims bind to MCT1 expressed by said cell.

119. The method according to claim 118, wherein the cell is non-human.

120. The method according to claim 118, wherein the cell is non-human.

121. The method according to claim 118, wherein the cell is obtained from a patient who has or is suspected of having an autoimmune condition, allergic condition, inflammatory condition, metabolic disorder, cancer, transplant recipient, cell therapy recipient, HIE condition, polycystic kidney disease (PKD)).

122. The method according to claim 118, wherein the detection method is used to diagnose or monitor a disease or disease diagnosis by using a cell sample obtained from a patient who has or is suspected of comprising an autoimmune condition, allergic condition, inflammatory condition, metabolic disorder, cancer, transplant recipient, cell therapy recipient, EIHI condition, polycystic kidney disease (PKD) characterized by cells comprising aberrant (increased) MCT1 expression or activity.