TUMOR INFILTRATION LYMPHOCYTE EXPANSION FROM LIQUID TUMORS AND THERAPEUTIC USES IN HEMATOLOGICAL NEOPLASMS.

Abstract

The present invention relates to a method for expanding peripheral blood lymphocytes (PBL) from peripheral blood, the method being characterized in that it comprises steps d: a. providing a sample of peripheral blood mononuclear cells (PBMCs) from the peripheral blood of a patient with a hematologic malignancy who has been previously treated with ibrutinib or another interleukin-2 inducible T-cell kinase (TKIT) inhibitor and who is refractory to treatment with ibrutinib or any other TKIT inhibitor, wherein the aminothiazole-based TKIT inhibitor, benzimidazole-based TKIT inhibitors, aminopyrimidine-based TKIT inhibitors, 3-aminopyrid-2-one-based TKIT inhibitors, indolindazole-based TKIT inhibitors, pyrazolyl-indole-based TKIT inhibitors, thienopyrazole-based TKIT inhibitors and TKIT inhibitors targeting cysteine-442 in the ATP pocket; b.cultivate said PBMCs in a culture comprising a first culture medium with IL-2 and anti-CD3 / anti-CD28 antibodies, thereby effecting the expansion of peripheral blood lymphocytes (PBLs) from said PBMCs; and c. harvest the PBLs from the culture in step b, wherein the method is carried out for a selected time period from the group consisting of: approximately 9 days, approximately 10 days, approximately 11 days, approximately 12 days, approximately 13 days, and approximately 14 days, and wherein the expanded PBLs comprise higher levels of IFNγ production than those expanded from patients not previously treated with ibrutinib or another KT1 inhibitor.

Description

EXPANSION OF TUMOR INFILTRATING LYMPHOCYTES FROM LIQUID TUMORS ¥ THERAPEUTIC USES OF THE SAME field of invention Methods for expanding tumor infiltrating lymphocytes (TILs), derived from the blood and / or bone marrow of a patient with a hematologic neoplasm, such as a fluid tumor, including lymphomas and leukemias, and compositions comprising populations of TILs derived from these are described herein. What's more,. The therapeutic uses of TILs expanded from the. blood or bone marrow from a patient with a hematologic malignancy, such as a fluid tumor, including en. the treatment of such hematologic malignancies, are described herein. Background of the Invention Treatment of bulky, refractory cancers using adoptive autologous transfer of tumor-infiltrating lymphocytes (TILs) represents a powerful approach to therapy for patients with poor prognosis. Gattinoni, et al, ATat. Rév, Immu.ná.1. 2006, 6, 3'83-393. TILs are dominated by T cells, and IL-2-based expansion of TILs followed by "process:rapid expansion" (RED) has become a preferred method for ITL expansion due to its speed and efficiency. Dudley, et al., Science 200:2, 298, -850-54; Dudley, et al., J. Clin. Oncol. 2005, 23, 2.34.6-57; Dudley, et al., J. Clin. Oncol. 2-Q08, 26, 5233-39; Riddell, et al., Science 1992, 257, 238-41; Dudley, et al., J. Immunother. .2003, 26, 332-42. A number of approaches to improve responses to TIL therapy in melanoma and expand TIL therapy to other tumor types have been explored with limited success, and the field remains unchanged. Goff, et al., J. Clin. Onecí. 2016, 34, 2389-97; Dudley, et al., J. Clin. Oncol. 2008, 26, 5233-39; Rosenberg, et al. , Clin. cancer wow .2011, 17, 4550-57. Early procedures for expansions of TILs from B-cell lymphomas provide poor results, with only 2 of 12 attempts at growth of TILs providing potential activity against tumors. Schwartzentruber, et al., Blood 1993, 82, 1204-1211. There is an urgent need to provide more effective therapies in many hematologic malignancies, including acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). The. The present invention provides the surprising finding that TIL expansion processes can result in efficient TIL populations derived from hematologic malignancies, such as heart fluid tumors, including lymphomas or leukemias. Brief Description of the Invention In one embodiment, the invention provides a method of treating a cancer with a population of tumor-infiltrating lymphocytes (TILs) comprising the steps of: (a) optionally pre-treating a patient with a regimen comprising at least one inhibitor of kinase; (b) obtaining a tumor from the patient by resection, biopsy, needle aspiration, or apheresis, the tumor comprising a first population of TILs, (c) optionally fragmenting or dissociating the tumor to obtain tumor fragments and put into contacting the tumor fragments with a first cell culture medium; (d) performing an initial expansion of the first population of TILs in the first cell culture medium to obtain a second population of TILs, where the second population of TILs is at least 5-fold greater in number than the first population of TILs, wherein the first cell culture medium comprises IL-2, and wherein the initial expansion is performed over a period of 21 days or less; (e) performing a sec An expansion of the second population of TILs in a second cell culture medium to obtain a third population of TILs, wherein the third population of TILs is at least 50-fold greater in number than the second population of TILs after 7 days a from the start of The Second Expansion; wherein the second cell culture medium comprises IL-2, OKT-3 (anti-CD3 antibody), and irradiated a.lcgenic peripheral blood mononuclear cells (P'BMCs), and wherein the second expansion is performed over a period of 14 days or less; (f) collecting the third population of TILs; and (g) administering a therapeutically effective portion of the third population of TILs to a patient with the cancer; wherein the tumor is a liquid tumor, and wherein the cancer is a hematologic malignancy. In one embodiment, the invention provides a method of treating a cancer with a population of tumor-infiltrating lymphocytes (TILs) comprising the steps of: (a) optionally pre-treating a patient with a regimen comprising at least one inhibitor of kinase; (b) obtaining a tumor from the patient by resection, biopsy, needle aspiration, or apheresis, the tumor comprising a first population of TILs; (c) optionally fragmenting or dissociating the tumor to obtain tumor fragments and contacting tumor fragments with a first cell culture medium; (d) performing an initial expansion of the first population of TILs in the first cell culture medium to obtain a second population of TILs, wherein the second population of TILs is at least 5-fold greater in number than the first population of TILs, where the first cell culture medium comprises IL-2, and where the initial expansion is performed over a period of 21 days or less, (e) perform a se second expansion of the second population of TILs in a second cell culture medium to obtain a third population of TILs, wherein the third population of TILs is at least 50-fold greater in number than the second population of TILs after 7 days from the start of the second expansion; wherein the second cell culture medium comprises irradiated IL-2, OKT-3 (anti-CD3 antibody), and allogeneic peripheral blood mononuclear cells (PBMCs), and wherein the second expansion is performed during a period of 14 days or less; (f) collect the third population of TILs; and (g) administering a therapeutically effective portion of the third population of TILs to a patient with the cancer; wherein the tumor is a liquid tumor, and wherein the cancer is a hematologic malignancy selected from the group consisting of acute myeloid leukemia (fAML), mantle cell lymphoma (MCL ) , follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), DLBCL activated B-cell (ABC) ., DLBCL .de . Germinal Central B Cell (GCB), Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Leukemia (SLL), Non-Hodgkin's Lymphoma (NHL) English), Hodgkin's lymphoma, relapsed and / or refractory Hodgkin's lymphoma, B-cell acute lymphoblastic lymphoma (B-ALL), mature B-ALL, Burkitt's lymphoma, Waldenstrom's macroglobulinemia (WM, for its acronym in English), multiple myeloma, myelodysplastic syndromes, myelofibrosis, leu chronic myelocytic anemia, follicular center lymphoma, indolent NHL, human immunodeficiency virus (HIV)-associated B-cell lymphoma, and Epstein-B-arr virus (EBV)-associated B-cell lymphoma , for its acronym in English). In one embodiment of the invention, the method further comprises adding an ITK inhibitor. In one embodiment, the ITK inhibitor is added to the cell culture medium during at least one of steps (d) and (e). In one embodiment of the invention, the ITK inhibitor. is a covalent ITK inhibitor that covalently and irreversibly binds ITK. In one embodiment of the invention, the ITK inhibitor. is an allosteric ITK inhibitor that binds to ITK. In another embodiment, the ITK inhibitor is selected from the group consisting of ammotazol-based ITK inhibitors, benzimide-based ITK inhibitors, aminopyridine-based TKI inhibitors, 3-amihopiridc-2-one-based TKI inhibitors, indolindazole-based TKI inhibitors, pyrazolyl-indole-based inhibitors, thienopyrazole inhibitors, and cysteine-442-targeted TKI inhibitors in the ATP cavity. In another embodiment, the ITK inhibitor is ibrutinib, dasatinib, bosutinib, nilotinib, erlotinib BMS509744, CTA056, GSK225O66.5A, PF06465469 ( (R) -'3-(1-(1-acryloylpi.peridin-3-11)- 4-amino-l.rt-pyrazolo[3,4-d]pyrimidin--3-yl)-N-(3-methyl-4-(1-methylethyl))benzamide), and combinations thereof. In another embodiment, the ITK inhibitor is ibrutinib. In another embodiment, the ITK inhibitor is (R)-3-(1-(1- acryloylpiperidin-3-yl)-4-amino·-lH-pyrazolo[3,4-d]pyrimidin-3-yl)-(3-methyl-4-(,1-methylethyl))benzamide. The above ITK inhibitors are commercially available from a number of sources, including Tocris Bioscience, Inc. (Minneapolis, MN, USA), Selleckchem, Inc. (Houston, TX, USA), and AK Scientific, Inc. (Union City , GA, USA). In another embodiment, the ITK inhibitor is added at a concentration from about 0.1 nM. to about 5 uM. In another embodiment, the ITK inhibitor is added at a concentration of from about 0.1 n.M to about 5 μM. In another embodiment, the ITK inhibitor is added at a concentration of from about 0.1 nM to about 100 nM. In another embodiment, the ITK inhibitor is added at a concentration of from about 0-5 nM to about 50 nM. In another embodiment, the ITK inhibitor is added at a concentration of from about 1 nM to about 10 nM. In one embodiment, the ITK inhibitor is added at a concentration of approximately 0.01nM, 0.05nM, 0.1nM, 0.5nM, 1uM, 2nM, 5nM, 10nM, 20nM, 30nM, 40nM, 50nM. , 60nM, 70nM, 80uM, 90nM, 100nM, 150nM, 200nM, 300nMf 400nM, 500nM, 600nM, 700nM, 800nM, 900nM, 1μΜ, 2μΜ, 3μΜ , 4 μΜ, 5 μΜ, 10 μΜ, 20 μΜ, 30 μΜ, 40 μΜ, and 50 μΜ. In one embodiment of the invention, a method for expanding peripheral blood lymphocytes (PBLs) from peripheral blood comprises: a. Obtaining a sample of peripheral blood moncnuclear cells (PBMCs) from peripheral blood, wherein such sample is optionally cryopreserved; b. Isolate PBLs a. from such a sample by selecting and removing CD19+ B cells; c. Optionally, cc-culture such PBLs with such CD19+ B cells; d. Stimulate such PBLs in a first cell culture medium with IL-2 and anti-CD3 / anti-CD28 antibodies for a period of about 2 days to about 6 days in a gas-permeable container; and. Cultivate the PBL-s from step (d) for a period of about 2 days to about 6 days with IL-2 and anti-CD3 / anti-CD28 antibodies; f. Isolate the PBLs bound to the antibody from the culture in step (e); g. Removing the antibodies from the PB'Ls isolated in step (e); yh. Collect the PBLs. In one embodiment of the invention, the method further comprises adding IL-2 after step (d), and exchanging the first culture medium with a second cell culture medium. In another embodiment, the method further comprises , adding IL-2 after step (e), and exchanging the second culture medium with a third culture medium. In one embodiment, the first cell culture medium, second cell culture medium, or third cell culture medium is selected from the group consisting of CM-2, CM-4, and AEVI-V. In another embodiment, the first and second cell culture media are the same. In another embodiment, the first and second cell culture media are different. In one embodiment of the invention, one or more of the first, second and third cell culture media are the same. In another embodiment, the first, second, and third cell culture media are all different. In one embodiment, optional co-cultivation of such PBLs with such CD19+ B cells is performed for a period of 1 hour up to 3 days. In one embodiment of the invention, the ratio of T cells to B cells in step (c) is from about 0.1:1 to about 10:1 (B-cells:T-cells). In another embodiment, the ratio of B-cells to T-cells in step (c) is selected from the group consisting of 0.1:1, 1:1, and 10:1 (B-cells; T). In one embodiment of the invention, the starting cell number of PBLs at the beginning of step (d) is at least from about 1x10.5 to about 10x105 PBLs. In another embodiment, the starting cell number of PBLs at the beginning of step (d) is at least from about 2.5x105 to 10x105 PBLs. In another embodiment, the starting cell number of PBLs at the beginning of step (d) is at least SxlO5 PBLs. In one embodiment of the invention, the IL-2 in each of steps f) and (d) is used at a concentration of from about 1000 IU / mL to about 6000 IU / mL. In another embodiment, the IL-2 in each of steps (c) and (d) is used at a concentration of about 3000 IU / mL< In one embodiment of the invention, anti-CD3 / anti-CD28 antibodies are coated on beads. In one embodiment of the invention, the anti-CD.3 / anti-CD28 antibodies are DynaBeads4. In one embodiment, the method includes co-culturing the anti-CD3 / anti-CD28 antibody beads with the PBLs in approximately a 1:1 bead:PBL ratio in each of steps (c) and (d). In one embodiment of the invention, the method comprises adding an ITK inhibitor. In one embodiment, the ITK inhibitor is added during at least one of steps (c), (d), and (e). In one embodiment of the invention, the ITK inhibitor is selected from the group consisting of aminothiaz-ol-based ITK inhibitors, benzimidazole-based ITK inhibitors, aminopyridine-based ITK inhibitors, 3-aminopyrido-2-one-based ITK inhibitors, indolyhdazole-based ITK inhibitors, pyrazol.il-indo!.-based inhibitors, thienopyrazcl inhibitors, and cysteine-442-targeting ITK inhibitors in the cavity ATP. In another embodiment, the ITK inhibitor is ibrutinib, dasatinib, bosutinib, nilotinib, erlotinib BMS50974.4, CTA05S, GSK2250665A, PF0'6465469, and combinations thereof. In another embodiment, the ITK inhibitor is ibrutinib. In one embodiment of the invention, any of the above methods for preparing PBLs is performed in a closed, sterile system. In one embodiment of the present invention, a method of expanding peripheral blood lymphocytes (PBLs) from. Peripheral blood includes: a. Obtain a sample of PBMCs from. peripheral blood, wherein such sample is optionally cryopreser vated; b. Isolate PBLs from such a sample by selecting and removing CD19+ B cells; c. -Co-culturing such PBLs with such CD194 B cells for a period of 4 days; d. Add about 2.5x105 to about 5x105 cells to a gas-permeable container in CM-2 cell culture medium and stimulate such PBLs with 3000 μl / ml of IL-2 anti-CD3 / anti-CD28 antibodies immobilized on beads per a period of approximately 4 days; e. Exchange CM-2 cell culture medium with AIM-V and additional IL-2· at approximately 3000 ΙΠ / ml;f. Culture the PBLs from step (e) for an additional period of approximately 3 days with IL-2 and ari-CD3 / anti-CD2 8s antibodies immobilized on beads; g. Isolate antibody-bound PBLs from stage 1 culture (f); h. Remove the antibodies from the PBLs isolated in step (g); yi. Collect the PBLs. In one embodiment of the invention, a method of treating a hematologic malignancy comprises: a. Obtaining a sample of PBMCs from the peripheral blood of a patient suffering from a hematologic malignancy; b. Isolate PBLs from such a sample by selecting and removing CD19+ B cells; c. Optionally co-culturing such PBLs with such CD19+ B cells; d. Stimulate such PBLs in a first cell culture medium with IL-2 and anti-CD3 / anti-CD28 antibodies for a period of at least about 4 days in a gas-permeable container; e to C-V1.1.x var the PBLs from step (d) for a period of 3 days with IL-2 and anti-CD3 / anti-CD28 antibodies; F. Isolate the PBLs bound to the antibody from the culture at stage Ce);g. Remove the antibodies from the PBLs isolated in step (e); yh. Collect the PBLs; yi. Administering the PBLs to the patient in a therapeutically effective amount to treat such hematologic malignancy In one embodiment of the invention, the method further comprises obtaining a PBMC sample from a patient that is pre-treated with an ITK inhibitor. In one embodiment of the invention, the ITK inhibitor is selected from the group consisting of aminothiazole-based ITK inhibitors, inhibitors. Benzimidazole-based ITKs, aminopyridine-based ITKs, 3-aminopyrido-2-anas-based ITKs, ITKs. indolindazole-based inhibitors, pyrazolyl-indo!-based inhibitors, thienopyrazole inhibitors, and cysteine-directed ITK inhibitors-- 442 in the ATP pocket. In one embodiment of the invention, the ITK inhibitor is ibrutinib, BMS509744, CTA056, GSK2250665A, PF064.6S469, and combinations thereof. In another embodiment, the ITK inhibitor is ibrutinib. In another embodiment, the patient is pre-treated with at least three rounds of an ibrutinib regimen. In one embodiment of the invention, the hematologic malignancy is selected from the group consisting of acute myeloid leukemia (SMA), mantle cell lymphoma (MCL), follicular lymphoma (FE), diffuse large B-cell lymphoma (DLBCL), DLBCL of activated B cells (ABC),. Germinal Central B-Cell (GCB) DLBCL, Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Leukemia (SEL), Non-Hodgkin's Lymphoma (NHE), Hodgkin's Lymphoma, Relapsed and / or Refractory Hodgkin's Lymphoma, B-cell Acute Lymphoblastic Lymphoma (B-ALL), mature B-ALL, Burkitt lymphoma, Waldenstrom macroglobulinemia (WM), multiple myeloma, myelodysplastic syndromes, myelofibrosis, chronic myelocytic leukemia, follicular center lymphoma, indolent NHL, immunodeficiency virus-associated B-cell lymphoma human (.HIV) . and Epstein-Barr virus (EBV)-associated B-cell lymphoma ... In another embodiment, the hematologic malignancy is chronic 1-lymphocytic leukemia (CLL). In a. In one embodiment of the invention, the PBLs are administered in an amount of from about 0.lxlO3 to about 15xlGs PBLs. In one embodiment of the invention, a method for expanding marrow infiltrating lymphocytes (MILs) from bone marrow comprising a. Obtain a sample of peripheral blood mononuclear cells (PBMCs) from. bone marrow..., wherein such sample is optionally cryopreserved; b. Classify a fraction of CD3 + , CD33 + , CD2Q + and CD14 + cells (MIL fraction) and a fraction of non-CD3 + -, non-CD33 + , non-CD20 + , non-CD14 + cells (fraction of AMÉ blast cells); c. Optionally alter the b1aSt os cell fraction of AM L;d. Add the optionally disrupted AML blast cell fraction to the MIL fraction in a cell number ratio of from about 0.1:1 to about 10:1 6. Culture one or both cell fractions in a gas-permeable container in a first cell culture medium, comprising IL-2; F. Stimulate MILs with anti-CD3. / anti-CD28 antibodies to obtain expansion of MILs; g. Re-stimulate MILs with IL-2 and anti-CD3 / anti-CD28 antibodies for an additional period of about 2 to about 6 days; h. Culture the MILs with additional IL-2 for an additional period of from about 1 to about 3 days; yi. Collect such MILs. In one embodiment of the invention, the method further comprises adding IL-2 after step (eg, and exchanging the culture medium with a second cell culture medium. In one embodiment, the first cell culture medium and the second cell culture media are selected from the group consisting of CM-2, CM-4, and AIM-V In another embodiment, the first and second cell culture media are the same In another embodiment, the first and the second cell culture medium are different. In one embodiment, there are al. least from about 2x104 to about 5x105' MILs in the gas permeable container at the beginning of step (e). In another embodiment, there are at least about 2.8x10* to 3.4x1.0s M'ILs in the gas-permeable container at the beginning of step (e). In another mode, there are at least. 5x10.5 MIL-s in the gas-permeable container at the beginning of step (e). In one embodiment of the invention, IL-2 is present at a concentration of between 10Q0 lü / 'ml and 6,000 IL / ml in the stage (eg. In another embodiment, IL-2 is present at a concentration of about 6000 IU / mL, In another embodiment, IL-2 is present at a concentration of approximately 3000 IU / mL in step (g) In another embodiment, IL-2 is present at a concentration of approximately 3000 IU / mL. ml in step (h). In. In one embodiment of the invention, the culture in step (e) is carried out for a period of approximately 3 days. In one embodiment, the stimulation in step (f) is carried out for a period of about 4 days. In one embodiment, the stimulation in step (g) is carried out for a period of about 7 days. In one embodiment of the invention, the optionally altered cell fraction is altered using a method selected from the group consisting of sonication, homogenization, vortexing, vibration, and lysis. In one embodiment of the invention, the non-CD3+, non-CD33+, non-CD20+, non-CD14+ cell fraction (AML blast fraction) is lysed using a suitable lysis method, including high temperature lysis. , chemical lysis (such as organic alcohols), enzymatic lysis, and other methods of cell lysis known in the art. In one embodiment of the invention, anti-CD3 / anti-CD28 antibodies are -coated onto beads and the ratio of MILs:beads is approximately 1:1 in each of steps (f) and (g). In one embodiment of the invention, the method is performed in a closed, sterile system. In one embodiment of the invention, a method for expanding marrow infiltrating lymphocytes (MILs) from bone marrow comprises: a. Obtaining a sample of peripheral blood mononuclear cells (PBMCs) from bone marrow, wherein such sample is optionally cryopreserved; b. classify one fraction of CD3+, CD33+, CD20+ and CD14-Í- cells (MIL cell fraction) and a fraction of non-CD3+, non-CD33 + , non-CD2.Q+, non-CD1.4-J- cells ('fraction of blast cells of AML); C. Disrupt the AML blast cell fraction and add the disrupted AML · blast cell fraction to a MIL cell fraction in a cell number ratio of approximately 1:1; d. Culture the -cell fractions in a gas-permeable container with . a first cell culture medium comprising IL-2 at about 6000 Ιϋ / ml for a period of about 3 days; and. Add anti~CD3. / anti-CD2.8 antibodies immobilized on beads to the cell culture at a ratio of approximately 1:1 (MIL-s :beads) and culture the ,MI:Ls and antibodies by a period of about 1 day; f. Exchange the first cell culture medium with a second cell culture medium comprising additional IL-2 a. about 3000 iu / ml; g. Culture the antibodies and MILs for an additional period of approximately 3 days; h. Restimulate MILs with IL-2 and anti-CD3 / anti-CD28 antibodies immobilized on beads for an additional period of at least about 4 days; i. . Exchange the second cell culture medium with a third cell culture medium comprising additional IL-2 at about 3000 Ιϋ / ml for an additional period of at least about 3 days; j. Collect such MILs. In a. embodiment of the invention, a method of treating a hematologic malignancy comprises: a. Obtaining a sample of peripheral blood mononuclear cells (PBMCs) from bone marrow, wherein such sample is optionally cryopreserved; b. Classify a fraction of CD3+, CD33+, CD20+ and CD14 + cells (MIL· fraction) and a fraction of non*· C.D3+, non-CD33+, non-CD20+, non-CD14 + cells (fraction of ΆΜ1 blast cells); c. optionally altering the AML blast cell fraction; d. Add the optionally altered "AML blast cell" fraction to the MIL fraction in a cell number ratio of from about 0.1:1 to about 10:1; e. Cultivating one or both cell fractions in a gas permeable container in a first cell culture medium comprising IL~2;f. Stimulate such a sample with anti-CD3 / anti-CD28 antibodies; g. Restimulate MILs with IL-2 and anti-CD3 / anti-CD28 antibodies for an additional period of at least approximately 4 days; h. Culture MILs with additional IL-2 for an additional period of at least about 3 days; i. Collect' such MILs; and j. Administering such MILs to a patient in a therapeutically effective amount to treat the hematologic malignancy. In. In one embodiment of the invention, the hematologic malignancy is selected from the group consisting of acute myeloid leukemia (AML), mantle cell lymphoma (MCL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Activated δ-Cell (ABC) DLBCL, Germinal Central B-Cell (GCB) DLBCL < Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Leukemia (SLL), Non-Hodgkin's Lymphoma (NHL), Hodgkin's Lymphoma, Recurrent Hodgkin's Lymphoma and / or refractory., B-cell acute lymphoblastic lymphoma (B'-ALL), mature B-ALL, Burkitt's lymphoma, Waldenstrom's macroglobulinemia (WM), multiple myeloma, myelodysplastic syndromes, myelofibrosis, chronic myelocytic leukemia, follicular center lymphoma, NHL indolent, human immunodeficiency virus (HIV)-associated B-cell lymphoma, and Epstein-Barr virus (EBV)-associated B-cell lymphoma. In another embodiment, the hematologic malignancy is acute myelogenous leukemia (AML). In one embodiment of the invention, the MILs are administered in an amount from about 4xl08 to about 2.5x10-MI'Ls. Brief Description of the Figures waRvoMrVvKsvaeAMrtnMMevMMttccvweenRUmAWWwwwwwwwwinnMmmrawwinnmmrawvwwwvvvMVMnnHMMveSRMMrtMvvvMMM* The foregoing summary, as well as the following detailed description of the invention, will be better understood when read in conjunction with the accompanying drawings. Figure 1 illustrates pathology information pairs, lymphoma tumors. Figure 2 illustrates a comparison of different subsets of lymphoma and melanoma TILs, showing that effector memory (EM) subsets in lymphoma TILs are significantly higher than EM subsets in melanoma TILs. Figure 3 illustrates a comparison of different subsets of lymphoma and melanoma TILs, showing that CD28*CD4* subsets in lymphoma TILs are significantly higher than these subsets in melanoma TILs. Figure 4 illustrates a comparison of CD4* T cell subsets of non-Hodgkin's lymphoma TILs and melanoma TILs, showing differentiation markers. The open bars in the graphs represent median values. CM refers to central memory T cells, EM refers to T cells. effector memory, and TEMRA refers to effector memory CD45RA+ T cells. Figure 5 illustrates a comparison of non-Hodgkin's lymphoma TILs CD-8* ​​cell subsets and melanoma TILs, showing markers of differentiation. The open bars in the graphs represent median values. CM refers to central memory T cells, EM refers to effector memory T cells, and TEMRA refers to effector memory CD45RA+ T cells. Figure 6 illustrates a comparison of CD4+ T cell subsets of non-Hodgkin's lymphoma TILs and melanoma TILs, showing marker depletion. Open bars in graphs represent median values. LAG3 refers to lymphocyte activation gene 3, PD1 refers to programmed death 1, and TIGIT refers to T-cell immunoreceptor with Ig and ITIM domains. Figure 7 illustrates unci, CD8 + T cell subset comparison of non-Hodgkin's lymphoma TILs and melanoma TILs, showing markers of depletion. The open bars in the graphs represent median values. LAG3 refers to lymphocyte activation gene 3, PD1 refers to programmed death 1, and TIGIT refers to T cell immunoreceptor with Ig and ITIM domains. Figure 8 illustrates a cell type comparison between non-Hodgkin's lymphoma TILs and melanoma TILs. NK refers to natural killer cells, and TCRab refers to cells that express a T-cell receptor with alpha and beta chains. Figure 9 illustrates b.ioluminescent redirected lysis (BRLA) assay results. Figure 10 illustrates results of interferon-γ enzyme-linked immunosorbent assay (I'FN-γ) for lymphoma TILs versus melanoma TILs. Figure 11 illustrates enzyme-linked immunospot assay (ELIspot) results for 1-infama TILs. Figure 12 illustrates ELIspot assay results for melanoma TILs. Figure 13 illustrates the results of NANOSTRIHG NCOÜNTER analysis, showing which lymphoma TILs express higher levels of .RORC IL17A (TH17 phenotype) and GATA3 (Th2 phenotype) compared to melanoma TILs. The respective genes are highlighted in white boxes on the heat map, Figure 14 illustrates a TIL expansion and treatment process. Stage 1 refers to the addition of 4 tumor fragments in 10 G-Rex 10 flasks. In stage 2, approximately 40 x 10s TILs or more are obtained. In stage 3, a division into 36 G-Rex 10 0 flasks per REP occurs. The TILs are collected by centrifugation in step 4. The fresh TIL product is obtained in step 5 after a total processing time of approximately 43 days, at which point the TILs can be infused into a patient. Figure 15 illustrates a treatment protocol for use with TILs derived from lymphoids of the present description. Surgery (and resection, of the tumor) occurs initially, and chemolymphodepletion refers to non-myeloablative lymphodepletion with chemotherapy as described elsewhere herein. Figures 16A-16D demonstrate the results of flow cytometric analysis using the standard DF2 phenotype panel described in Example 4, below. The TILs of lymphoma and melanoma. were stained using the BF2 standard phenotype panel as described: in Example 4. The data shown represent different subpopulations of total CD4 and CD8 T cells in TIL. Figure 16A demonstrates the ratio of CD4 and CD8 cells to T cell subsets. no prior treatment; Figure 16B for central memory (CM) T-cell subsets. Figure 16C for effector memory (EM) T-cell subsets, and Figure 16D for terminally differentiated effector memory T-cell (TEMRA) subsets. P were calculated using the two-tailed (unpaired) Mann-Whitney Test. The mean proportion of cell subsets is presented by horizontal bars. Figures 17A and 17B demonstrate the results of flow cytometry analysis using the DF1 standard phenotype panel as described in Example 4, below. TILs from lymphoma and melanoma were stained using the DF1 standard phenotype panel, as described in Example 4. The data shown represent different subpopulations of CD2 7+ (Figure 17A), and CL2 8+ (Figure 17B) of CD4 T cells. and total CD'9 on TIL, indicating a higher proportion of CD4 T cells expressing CD28 costimulatory molecules on lymphoma TIL. P-values ​​were calculated using the two-tailed (unpaired) Mann-Whitney Test. Figures 18A and 18B demonstrate the results of an interferon-gamma (IFN-γ) assay conducted in accordance with Example 4, below. Figure 18A demonstrates the results using ELIspot. ELIspot data are expressed as IFN-γ producing cells per 106 TIL. Figure 18B demonstrates the results using ELISA. ELISA data are expressed as IFN-γ levels in supernatants. TIL cultures at 5x105 TIL / well) as measured by ELISA (log-scale P-values ​​were calculated using the two-tailed Mann-Whitney Test (unpaired). Figures 19A and 19B demonstrate the lytic potential of TIL. Figure 19A LU50 of target cells normalized to 10s TIL at 4 hours (FIG. 19A) and 24 hours (FIG. 19B) in co-culture (TIL effector cells with GFP+P815 target cells). Figures 20A-2QD demonstrate the cytolytic activity of different TILs against allogeneic and autologous tumor types. Figure 20A shows the cytolytic activity of melanoma TIL against allogeneic S2S target cells. Figure 20B shows the cytolytic activity of lymphoma TIL against autologous tumor cells as determined by 7-AAD uptake. Data in Figures 2QA and Figure 20B are shown as percentages of dead cells in co-cultures with a 50:1 target:effector cell ratio (E:T). Figure 20C depicts the percentage kill of target cells induced by melanoma TILs. Figure 2'OD represents the percent kill of TIL-induced target cells from lymphoma at different E:T ratios. Figure 21 is a heat map showing the TIL gene expression profiles of lymphoma and melanoma. Expression profiles were determined by NanoString's 579 plex nCounter GX Human Immunology V2 CSO panel. The heat map shows the fold change in expression of a particular set of genes in . Lymphoma TIL compared to melanoma TIL, and suggests superior expression of IL-17A and RORC from lymphoma-derived TIL. Cancers shown in this figure include follicular lymphoma (EL), diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCLj. Figure 22 is a schematic demonstrating the 2A process for ITL preparation, collection and transportation scheme. Figure 23 is a flow chart demonstrating the process. 2Ά to prepare TIL. Figures 24A--24C are flow charts demonstrating three different methods for expanding Peripheral Blood Lymphocytes (PBLs). Figures 25A-25C depict three different methods for expanding marrow infiltrating lymphocytes (MILs) from bone marrow. Figure 26 depicts a fold expansion graph for PBLs isolated from fresh peripheral blood nuclear cells (PBMCs) and from PBMCs. cryopreserved. Cryopreserved PBMCs are derived from CLL patients who have not been (PreRx PBL) or who have been (PostRx PBL) treated with an ibrutinib regimen. For each of Figures 26-34B, each point is a patient. Shaded points are patients whose PBLs are expanded using PBL Method 1; open points are patients whose PBLs are expanded using PBL Method-2; black dots are patients whose PBLs are expanded using PBL Method 3. Figure 27 depicts a graph of IFN-γ producing cells for PBLS isolated from fresh PBMCs and cryopreserved PBMCs. Within the cryopreserved PBMCs, PreRx PBLs and PostRx PBLs are also represented, Figure 28 depicts the ratio of CD4+- and CD8+ T cell subsets in PBL PreRx and PBL PostRx, using raelanoma TIL as a comparator. Figures 29A-29D and Figures 30A-30D depict a comparison between CD4 (Figures 29A-29D) and CD8 (Figures 30A-30D) memory subsets: of PreRx PBLs and PostRx PBLs, using melanoraa TIL as a comparator. Figures 29A and 30A show data for (CCR7+ / CD45RA+) naïve; Figures 29B and 30B show data for central memory (CM) T cells (CCR7+ / CD45RA-); Figures 29C and 30C show data for effector memory (EM) T cells (CCR7- / CD45RA-); and Figures 2 9D and 30D show data for terminally differentiated effector memory cells (TEMRA) (CCR7- / CD45RA+). Figures 31Ά and 3IB depict a CD27 subset comparison of CD4 (Figure 31A) and CD8-subsets (Figure 3IB) for PreRx PBLs and PostRjc PBLs, using melanoma TIL as a comparator. Figures 32A and 32Β depict a CD28 subset comparison of CD4 (Figure 3.2A) and CD8 subsets (Figure 32B) for P.reRX PBLs and PoStRx PBLs, using melanoma TIL as a comparator. Figures 33A and 33B depict a comparison of LAG3 + subseries within the CD4 (Figure 33A) and CD8 (Figure 33B) populations for both PreRx PBLs and PostRx PBLs. Figures 34A and 34B depict a comparison of PD1+ subsets within the CD4 (Figure 34A) and CD8 (Figure 34B) populations for both PreRx PBLs and PostRx PBLs. Figures 3 5A and 35B show results of the cytolytic activity of PreRx PBLs (Figure 35A) and PostRx PBLs (Figure 35B), measured using an autologous tumor clearance assay. The. Cytotoxicity is measured as the LUS0 (the number of PBLs required to kill 50% of the target cells). Figures 3SA and 3SE. plots of fold expansion are depicted for MILS (FIG. 36A) and PBLs (FIG. 36B) isolated from either bone marrow (MILs) or peripheral blood (PBLs) of AML patients. MILI.1 was expanded using MIL Method 1, MILI was expanded. 2 using MIL Method 2, and MILI was expanded. 3 using .MIL Method 3, MIL2 and MIL3 were expanded using MIL Method 3. All PBLs were expanded using PBL Method 3. The starting cell number for MILI.3- was 138,000 cells, for M.TL2 it was 62.0.00 and for MIL 3 it was 28,000 cells. The starting cell number for PBL2 was 338,000 and for PBL3 it was 330,000. Figures 37A and 37B illustrate cells that produce IFNγ for each of the MILs (Figure 37A) and PBLs (Figure 37B). Figures 38A-38F depict graphs illustrating T cell subsets in MILs (Figures 38A-38C) and PBLs (Figures 38D--38F) isolated from AML patients. Figures 38A and 38D illustrate TCRui3+ subsets, Figures 38B and 38S illustrate CD4+ subsets, and Figures 38C and 38F illustrate CD subsets. PBLs are shown on day 0 and on. on day 1,4. Figures 39A-39D depict graphs illustrating CD4 memory subsets for MILs isolated from AML patients. Figure 3 9A shows data for (CCR7+ / CD45RA*) naïve; Figure 39B shows data for central memory (CM) T cells (CCR7+ / CD45RA-); Figure 39C shows data for effector memory (EM) T cells (CCR7- / CD45RA-); and Figure 39D shows data for terminally differentiated memory cells (TEMRA) (CCR7- / CD45RA+). Figures 40A-40D depict graphs illustrating CD4 memory subsets for PBLs isolated from SMA patients. Figure 40A shows data for (CCR7+ / CD45RA+) naïve; Figure 40B shows data for central memory (CM) T cells (CCR7+ / CD45RA-); Figure 40C shows data for effector memory (EM) T cells '(CCR7- / .CD45RA-); and Figure 40D shows data for terminally differentiated memory cells (TEMRA) (CCR7- / CD45RA+). Figures 41A-41D depict graphs illustrating CD.8 memory substrings for MILs isolated from AM patients. Figure 41A shows data for (CCR7-Í- / CD4 5RA.-Í-) without prior treatment; Figure 41B shows data for central memory (CM) T cells (CCR7e / CD45RA·^) ; Figure 41C shows data for effector memory (EM) T cells (CCR7- / CD45RA-); and Figure 4ID shows data for terminally differentiated memory cells (TEMRA) (CCR7- / CD45RA+). Figures 42A-42D depict graphs illustrating CD8 memory subsets for PBLs isolated from AML patients. Figure 42A shows data for naive (CCR7+. / CD4 5RA+) ; Figure 42B shows data for central memory (CM) T cells (CCR7+ / CD45RA'); Figure 42C shows data for effector memory (EM) T cells (CCR7- / CD4 5RA-); and Figure 42D shows data for terminally differentiated memory cells (TEMRA) (CCR7- / CD45RA*). Figures 43A and 43B depict graphs illustrating CD27 subsets of CD4 and CD8 cell populations for MILs (Figure 43A) and PBLs (Figure 43B). Figures 44A and 44B depict graphs illustrating CD28 subsets of CD4 and CD8 cell populations for MILS (Figure 44A) and PBLs (Figure 44B). Figures 4-5A and 45B depict graphs illustrating PD1+ subsets of CD4 and CD8 cell populations for MILs (Figure -45A) and PBLs (Figure 4-5B). Figures 4 6A and 46B- depict graphs illustrating LAG3+ subsets of CD4 and CD8 cell populations for MILs (Figure 4&A) and PBLs (Figure 4 6B). Figure 4-7 is a timeline illustrating exemplary embodiments of PBL Method 1 and PBL Method 3. In this figure, the addition of IL-2 can take place at any time point during the process, and in an exemplary embodiment, over the area between brackets. Figure 48 is a timeline illustrating an exemplary embodiment of 'MIL Method 3'. In this figure, the addition of IL-3 can take place at any time point during the process, and in an exemplary embodiment, over the bracketed area. BRIEF DESCRIPTION OF THE LISTING OF SEQUENCES SEQ ID NO: 1 is the amino acid sequence of the heavy chain of muromonab. SEQ: ID NO:2 is the amino acid sequence of the light chain of muromonab. The SEQ ID NO:. 3 is the amino acid sequence of a recombinant human IL-2 protein. SEQ ID NO:4 is the amino acid sequence of al des'.' Holm oak, SEQ ID NO: 5 is the amino acid sequence of a recombinant human IL-4 protein. SEQ ID NO: 6 is the amino acid sequence of a recombinant human IL-7 protein. The. SEQ ID NO: 7 is the amino acid sequence of a recombinant human IL-15 protein. SEQ ID NO: 8 is the amino acid sequence of a. IL-21 protein. recombinant human. Detailed Description of the Invention Unless otherwise defined, all technical and scientific terms used herein have the same Meaning as commonly understood by one of skill in the art to which this invention pertains. All patents and publications referenced herein are incorporated by reference in their entireties. Definitions

[0089] The terms "co-administration", "co-administration", "administration in combination with*, "administration in combination with*", "simultaneous" and "concurrent*", as used herein, encompass the administration of two or more active pharmaceutical ingredients to a subject such that both the pharmaceutical ingredients and / or their metabolites are present in the subject at the same time Co-administration includes simultaneous administration in separate compositions, administration to different times in separate compositions, or administration in a composition in which two or more active pharmaceutical ingredients are present Simultaneous administration in separate compositions and administration in a composition in which both agents are present are preferred. The term "in vivo" refers to an event that takes place in a body of the mammalian subject. The term "ex vivo" refers to an event that takes place outside a mammalian subject's body, in an artificial environment. The term "in vitro" refers to an event that takes place in a test system. In vitro assays encompass cell-based assays in which living or dead cells may be used and may also encompass a cell-free assay in which non-intact cells are used. The term "rapid expansion" means an increase in the number of antigen-specific TILs of at least about 3-fold (or 4-, 5-, .6-, 7-, 8-, or 9-fold) during a one-week period, more preferably at least about 10-times (or 20-, 30-, 40-, 50-, 60-, 70-, 80-, or 90-times) over a one-week period , or most preferably at least about 100-fold over a one week period A number of rapid expansion protocols are described herein. The terms "fragmentation", "fragment", and "fragmented", as used herein, describe processes for disrupting a tumor, including mechanical fragmentation methods such as grinding, slicing, dividing, and morcellating tumor tissue. as well as any other method to alter the physical structure of the weave of the turnar. The terms "peripheral blood mononuclear cells '1 and "PBMCs." refer to a peripheral blood cell having a round nucleus, including lymphocytes (T cells, B cells, NK cells) and monocytes. Optionally, cells Peripheral blood mononuclear cells are irradiated allogeneic peripheral blood mononuclear cells. They are antigen presenting cells. The term "PBLs" refers to peripheral blood lymphocytes and are T cells expanded from peripheral blood. The terms PBL and TIL are used interchangeably herein.The term "anti-CDS antibody" refers to an antibody or variant thereof, for example, a monoclonal antibody, and includes human, humanized, chimeric, or marine antibodies, which are directed against the receptor. CD3 at the T-cell antigen receptor of mature T cells Anti~CD.3 antibodies include OKT-3, also known as muromonab, and UCHT-1 Other anti-CD3 antibodies include, e.g. example, otelixizumab, teplizumab, and visilizumab. The term "QKT-3'" (also referred to herein as "GKT3") refers. to a monoclonal or biosimilar antibody or variant thereof, including human, humanized, chimeric, or murine antibodies directed against the CD3 receptor on the T cell antigen receptor of mature T cells, and includes commercially available forms such as O.KT -3 (3Ό ng / mL, from pure GMP CD3 MACS, Miltenyi Biotech, Inc., San Diego, CA, USA) and muromonab or variants, conservative amino acid substitutions, glycoforms, or biosimilars thereof. The amino acid sequences of the heavy and light chains of muromonab are provided in Table 1 (SEQ ID NOcl and SEQ ID N0u-2). A hybridoma capable of producing OKT-3 was deposited with the Amaricano Type Culture Collection and assigned accession number ATCC CRL 8001. A hybridoma capable of producing OKT-3 was also deposited with the European Collection of Authenticated Cell Cultures (ECACC ) and assigned Catalog No. 8 6 0 22706. TABLE 1. Muromonab amino acid sequences. The term "IL-2" (also referred to herein as '\IL~2') refers to the cell growth factor known as interleukin-2, and includes all forms of IL-2 including human forms. and mammalian, conservative amino acid substitutions, glycoforms, biosimilars, and variants of them. il-2 is described, for example, in Nelson, J. Tmmunol. 200'4, 172, 3983-88 and Malek, Annu. Kevin. Immimol. 2008, .2.6, 4 53-79, the disclosures of which are incorporated by reference herein. The amino acid sequence of recombinant human IL-2 suitable for use in the invention is provided in Table 1 2 (SEQ ID NO: 3). For example, the term IL-2 encompasses human, recombinant forms of IL-2 such as -alde leucaria (PROLEUCIN, commercially available from multiple suppliers in 22 million TU per single-use vial), as well as the form of Recombinant IL-2 commercially available from CellGenix, Inc., Portsmouth, NH, USA (CELLGRO GMP) or ProSpec-Tany TechnoGéne Ltd., East Brunswick, NJ, USA (Cat. No. C¥T~20.9-b) and other commercial equivalents from other sellers. Aldesleukin (des-alanyl-1, human IL-2 serine-125) is a non-glycosylated recombinant human form of IL-2 with a molecular weight of approximately 15 kDa. The amino acid sequence of aldes1encin suitable for use in the invention is provided in Table 2 (SEQ ID NO:4). The term IL-2 also encompasses pegylated forms of IL-2, as described herein, including pegylated IL-2 prodrug NKTR-214, available from Nektar Therapeutics, South San Francisco, CA, USA. NKTR-214 and pegylated IL-2 suitable for use in the invention are described in US Patent Application Publication No. US 2-014 / 032879-.1 Al and International Patent Application Publication No. WO 2012 / 065086 Al, the disclosures of which are incorporated by reference herein. Alternative forms of conjugated IL-2 suitable for use in the invention are described in US Patent Nos. 4,766,106, 5,206,344, 5,089,261 and 4,902,502, the disclosures of which are incorporated by reference herein. IL-2 formulations suitable for use in the invention are described in US Patent No. 6,706,289, the disclosure of which is incorporated by reference herein. TABLE 2. Amino acid sequences of interleukins. The term "IL-4" (also referred to in present 1.a as "IL4") refers to the cytokine known as interleukin 4, which is produced by Th2 T cells and by eosinophils, basophils, and mast cells. IL-4 regulates differentiation, from naive T helper cells (.ThO cells) to Th2 T cells. Steinke and Borish, Hespir. Res. 2001, 2, 66-70. After activation by IL-4, Th2 T cells subsequently produce additional I'L-4 in a positive laugh-feeding loop. IL-4 also stimulates B cell proliferation and MHC class II expression, and induces IgE class switching and IgG1 expression of B cells. Recombinant human IL-4- suitable for use in the invention is commercially available. from multiple vendors, including ProSpec-Tany TechnoGene Ltd., East Brunswick, NJ, USA (Cat. No. CYT-211) and ThermoFisher Scientific, Inc., w-altham, MA, USA (recombinant human IL-15 protein, Gibco Cat. No. CTP0043). Lase owner i a of amino acid of IL-4. recombinant human suitable for use in the invention is provided in Table 2 (SEQ ID NO: 5). The term "IL-7" (also referred to herein as "117") refers to a glycosylated tissue-derived cytokine known as interleukin 7, which is obtained from stramal and epithelial cells, as well as also from dendritic cells. Fry and Mackall, Blood 2002, 99, 3892-904. IL-7 can stimulate T cell development. IL-7 binds to the IL-7 receptor, a. heterodimer consisting of IL-7 receptor alpha and common chain receptor gamma, which is a signal array important for T-cell development within the thymus and survival within the periphery. Recombinant human IL-7 suitable for use in the invention is commercially available from multiple vendors, including ProSpec-Tany TechnoGene Ltd., East Brunswick, NJ, USA (Cat. No. C'YT-254) and ThermoFisher Scientific. , Inc., Waltham, MA, USA (recombinant human IL-7 protein, Cat. No. Gibco PHC0071). The amino acid sequence of recombinant human IL-7 suitable for use in the invention is provided in x to Table 2 (SEQ ID NO; 6.). The term "IL-15" {also referred to herein as "IL15") refers to the T-cell growth factor known as interleukin-1.5, and includes all forms of .TL-15 including human and mammalian forms. , conservative amino acid substitutions, glycoforms, biosimilars, and variants thereof. IL-15 is described, for example, in Fehniger and Caligiuri, Blood 2001, 97, 14-32, the disclosure of which is incorporated by reference herein, IL-15 shares signaling receptor subunits. 5 and γ with IL-1.2. Recombinant human l.L-15 is a single, non-glycolic Hada polypeptide chain containing 11.4 amino acids (and an N-terminal methionine) with a molecular mass of 12.3 kDa. Recombinant human IL-15 is commercially available from multiple vendors, including ProSpec-Tany TechnoGene Ltd., East Brunswick, NJ, USA (Cat. No. CYT-230-b) and ThermoFisher Scientific, Inc., Waltham, MA, USA (recombinant human IL-15 protein, Cat. No. 34-8159-82). The amino acid sequence of recombinant human I.L-15 suitable for use in. the invention is provided in Table 2 (SEQ ID NO: 7). The term "IL-21" (also referred to herein as "TL2-1") refers to the pleiotropic cytokine protein known as interleukin-21, and includes all forms of IL-21 including mammalian forms. and human, conservative amino acid substitutions, glycoforms, biosimilars, and variants thereof. .IL·-21 is described, for example, in Spolski and Leonard, .Nat. Rev. Drug, Disc, 2014, 13: 379-95, the description of which is incorporated by reference herein. IL-21 is primarily produced by natural killer T cells and activated human CD4* T cells. Recombinant human IL-21 is a single, non-glycosylated polypeptide chain containing 132 amino acids with a molecular mass of 15.4 kDa. Recombinant human IL-21 is commercially available from multiple vendors, including ProSpeo-Tany TechnoGene Ltd., East Brunswick, NJ, USA (Cat. No. CYT-408-b) and ThermoFisher Scientific, Inc., Waltham, MA, USA (recombinant human IL-21 protein, Cat. No. 14-8219-80). The amino acid sequence of recombinant human TL-21 suitable for use in the invention is provided in Table 2 (SEQ ID NO: 8;. The terms "pharmaceutically acceptable carrier" or "pharmaceutically acceptable excipient" are intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and inert ingredients. The use of such pharmaceutically acceptable carriers or pharmaceutically acceptable excipients for active pharmaceutical ingredients is well known in the art Except insofar as any conventional pharmaceutically acceptable carrier or pharmaceutically acceptable excipient is compatible with the active pharmaceutical ingredient, their use in therapeutic compositions of the invention is contemplated Additional active pharmaceutical ingredients, such as other drugs, may also be incorporated into the compositions and methods described. The terms "antibody" and its plural form "antibodies" refer to whole immunoglobulins and any antigen-binding fragments ("antigen-binding portion") or single chains thereof. An "antibody" further refers to a glycoprotein comprising at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds, or an antigen-binding portion thereof. Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as VK.) and a light chain constant region. The heavy chain constant region is comprised of three CHI domains, CH2 and CH3. Each light chain is comprised of a light chain variable region (herein abbreviated as Vi,) and a light chain constant region. The light chain constant region is comprised of one domain, CL. The VE and Vl regions of an antibody can be further subdivided into regions of hypervariability, which are also referred to as complementarity determining regions (CDRs). or hypervariable regions (HVR), and which may be interspersed with regions that are less conserved, called framework regions (FR). Each 'V' and Vi, is composed of three CDRs and four FRs, arranged from the amino terminal to the carboxy terminal on it. following order: FR1, CDR1, FR2, CDR2, FRS, CDRS, FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen epitope or epitopes. The constant regions of antibodies can mediate immunoglobulin binding to host tissues or factors, including various cells of the immune system (eg, effector cells) and the first component (Clq) of the classical complement system. The term -"antigen" refers to a substance that induces an immune response. In some embodiments, an antigen is a molecule capable of being bound by an antibody or a TCR if presented by major histocompatibility complex (MHC) molecules. The term "antigen" as used herein also encompasses T-cell epitopes. An antigen is additionally capable of being recognized by the immune system. In some embodiments, an antigen is capable of inducing a humoral immune response or a cellular immune response leading to the activation of B cells and / or T cells. In some cases, this may require that the antigen contains or is linked to a Th-cell epitope. An antigen may also have one or more epitopes (eg, B and T epitopes). In some embodiments, an antigen will preferentially react, typically in a highly specific and selective manner, with its corresponding antibody or TCR and not with the host of other antibodies or TCRs, which may be induced by other antigens. The terms "monoclonal antibody", "mAb", "monoclonal antibody composition", or their plural forms refer to a preparation of antibody molecules of single molecular composition. A monoclonal antibody composition exhibits a unique binding specificity and affinity for a particular epitope. Monoclonal antibodies specific for certain receptors can be made using skill and knowledge in the art to inject test subjects with the appropriate antigen and then isolate hybridoma-expressing antibodies having the desired sequence or functional characteristics. The DNA encoding the monoclonal antibody is readily isolated and sequenced using conventional procedures (eg, using oligonucleotide probes that are capable of specifically binding to genes encoding the heavy and light chains of monoclonal antibodies). Hybridoma cells serve as a preferred source of such DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells such as E. calli cells, simian COS cells, Chinese hamster ovary (CHO) cells, or honeycomb cells. they do not otherwise produce immunoglobulin protein, to elicit monoclonal antibody synthesis in recombinant host cells. The recombinant production of antibodies will be described in more detail below. The terms "antigen-binding portion" © "antigen-binding fragment" of an antibody (or simply "antibody portion" or "fragment"), as used herein, refer to one or more fragments of an antibody. antibodies that retain the ability to specifically bind an antigen. It has been shown that the antigen binding function of an antibody can be performed by fragments of a full length antibody. Examples of binding fragments encompassed within the term "antigen-binding portion" of an antibody include (i): a Fab fragment, a monovalent fragment consisting of the Vl, Vh, Ci, and CHI domains; (ii) an F(ab'..)2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bond to the hinge region,- (iii) an Fd fragment consisting of the Vh and CHI domains, (iv) a fragment Fv consisting of the Vr and Vh domains of a single arm of an antibody, (v) an antibody domain fragment (dAb) (Ward, et al., Nature, 19-89·, 341, 544-546) , which may consist of a Vh or Vt domain, and (vi) an isolated complementarity determining region (CDR).In addition, although the two domains of the Fv fragment, Vl and Vh, are encoded by separate genes, they may be linked, using recombinant methods, by a synthetic linker that allows them to be made as a single protein chain in which the Vi, and Vh form monovalent molecules known as single chain Fvs (scFvs) see, e.g., Bird, et al., Science 1988, 242, 423-426; and Huston, et al., Proc. Nati. Atad, Sel. USA 1988, 85, 5879-5.8-83). Such scFv antibodies are also intended to be encompassed within the terms "antigen-binding portion" or "antigen-binding fragment" of an antibody. These antibody fragments are obtained using standard techniques known to those of skill in the art, and the fragments are screened for utility in the same manner as are intact antibodies. The term "intact antibody" as used herein is intended to include antibodies having variable regions in which both the CDR and framework regions are derived from human germline immunoglobulin sequences. Furthermore, if the antibody contains a constant region, the constant region is also derived from human germline immunoglobulin sequences. Human antibodies of the invention may include amino acid residues not encoded by human germline immunoglobulin sequences (eg, mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo). "human antibody", as used herein, is not intended to include antibodies in which CDR sequences derived from the germ line of other mammalian species, such as mouse, have been grafted onto human framework sequences. The term "human monoclonal antibody" refers to antibodies that exhibit a unique binding specificity which have variable regions in which both the CDR and framework regions are derived from human germline immunoglobulin sequences. In one embodiment, human monoclonal antibodies are produced by a hybridoma which includes a B cell obtained from a transgenic non-human animal, eg, a transgenic mouse, having a genome comprising a human heavy chain transgene and a light chain transgene fused to an immortalized cell. The term "recombinant human antibody" as used herein includes all human antibodies that are prepared, expressed, created, or isolated by recombinant means, such as (a) antibodies isolated from an animal (such as a mouse) that is transgenic or transchromosomal for human immunoglobulin genes or a hybridoma prepared therefrom (described further below), (b) antibodies isolated from a host cell transformed to express the human antibody, eg, from a transfectoma , (c) antibodies isolated from a combinatorial, recombinant human antibody library, and (d) antibodies prepared, expressed, created, or isolated by any other means involving splicing of human immunoglobulin gene sequences to other sequences. Such recombinant human antibodies have variable regions in which the CDR and framework regions are derived from immunogenic sequences. human germline obulin. In certain embodiments, however, such recombinant human antibodies can be subjected to in vitro mutagenesis (or, when an animal transgenic for human Ig sequences is used, somatic mutagenesis in vivo) and thus the amino acid sequences of the Vh and Vl regions of the recombinant antibodies are sequences that, while derived from and refer to human germline Vh and V, sequences, cannot exist naturally within the human germline repertoire of the antibody in vivo. As used herein, "isotype" refers to the class of antibody (eg, IgM or IgG1) that is encoded by the heavy chain constant region genes. The phrases "an antibody which recognizes an antigen" and "an antibody-specific for an antigen" are used interchangeably herein with the term "an antibody which specifically binds an antigen". The term "human antibody derivatives" refers to any modified form of the human antibody, including a conjugate of the antibody and another active pharmaceutical ingredient or antibody. The terms "conjugate", "antibody-drug conjugate", "ADC", or "immunoconjugate" refer to an antibody, or a fragment thereof, conjugated to another therapeutic moiety, which may be conjugated to antibodies described herein using methods available in the art. The terms "humanized antibody," "-.humanized antibodies," and "humanized" are intended to refer to antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences Additional framework region modifications can be made within the human framework sequences Humanized forms of non-human (eg, marine) antibodies are chimeric antibodies that contain minimal sequence derived from non-human immunoglobulin. For the most part, humanized antibodies are human immunoglobulins (recipient antibody) in which residues of a hypervariable region of the recipient are replaced by residues of a hypervariable region of a non-human species (donor antibody) such as mouse, rat, rabbit or nonhuman primate that has the desired specificity, affinity, and capacity In some cases, residues of the Fv framework region (FR) of the human immunoglobulin are replaced by corresponding non-human residues. In addition, humanized antibodies may comprise residues that are not found in the recipient antibody or the donor antibody. These modifications are made to further refine the performance of the antibody. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin sequence. The humanized antibody will optionally also comprise at least a portion of a human immunoglobulin (Fe) constant region, typically that of a human immunoglobulin. For additional details, see Jones, et al., Nature 1986, 321, 522-525; Riechmann, et al., Matare 1988, 332, 32.3-329; and Presta, Curr. Op. Struct. Biol 1992, 2, 593-596. The antibodies described herein may also be "modified to employ" any Fe variant which is known to impart an enhancement (eg, reduction) in FcR effector function, effector, and / or binding. Fe variants may include, for example, any of the amino acid substitutions described: in International Patent Application Publication Nos. WO 1988 / 07089 Al, WO 1996 / 14339 Al, WO 1998 / 05787 Al, WO 1998 / 23239 Al, WO 1999 / 51642 Al, WO 99 / 58572 Al, WO 2000 / 09560 A2, WO 2000 / 32767 Al, WO 2000 / 42072 A2, WO 2002 / 44215 A2, WO 2002 / 060919 A2, WO 2003 / 074569 A2, WO 2004 / 016750 A2, WO 2004 / 029207 A2, WO 2004 / 035752 A2, WO 2004 / 0633 51 A2, WO 2004 / 074455 A2, WO 2004 / 099249 A2, WO 2005 / 040217 A2, WO 2005 / 070963 Al,WO 2005 / 077981 A.2, WO 2005 / 092925 A2, WO 2005 / 123780 A2, WO 2006 / 01944'7 Al, WO 2006 / 047350 A2, and WO 2006 / 085967 A2; and Patents. US Nos, 5,648,260; 5,739,277; 5,834,250; 5,869,046; 6,096,871; 6 / 121,022; 6, 194,551; 6,242, 195; 6,277,375; 6,528,624; 6,538, 124; 6,737,056; 6,821,505; 6,998,253; and 7,083,784; the disclosures of which are incorporated by reference herein. The term "chimeric antibody" is intended to refer to antibodies in which the variable region sequences are derived from one species and the constant region sequences are derived from another species, such as an antibody in which the variable region sequences are derived from an antibody and the constant region sequences are derived from a human antibody. A "diabody" is a small antibody fragment with two antigen-binding sites. The fragments comprise a heavy chain variable domain (Vh) connected to a light chain variable domain (Vi.) on the same polypeptide chain (Vh-Vj, or Vl-%). Using a linker that is also short to allow pairing between the two domains on the same chain, the domains are spawned to pair with the complementary domains of another chain and create two antigen-binding sites. Diabodies are more fully described in, for example, European Patent No. EP 404,097, International Patent Application No. WO 93 / 11161; and Bolliger, et al., Proa. Nati. Acad. Sci. USA 1993, 90, 6444-6448. The term "glycosylation" refers to a modified derivative of an antibody. An aglycosylated antibody lacks glycosylation. Glycosylation can be altered to, for example, increase the affinity of the antibody for the antigen. Such carbohydrate modifications can be made by, for example, altering one or more glycosylation sites within the antibody sequence. For example, one or more amino acid substitutions can be made that result in the removal of one or more variable region framework glycosylation sites to thereby eliminate glycosylation at that site. Aglycosylation can increase the affinity of the antibody for the antigen, as described in US Patent Nos. 5,714,350 and 6,350,861. Additionally or alternatively, an antibody can be made that has an altered type of glycosylation, such as a hypofucosylated antibody that has reduced amounts of fucosyl residues or an antibody that has increased bisecting GlcNác structures. Such altered glycosylation patterns have been shown to increase the capacity of antibodies. Such carbohydrate modifications can be made by, for example, expressing the antibody in a host cell with. altered glycosylation machinery. Cells with altered glycosylation machinery have been described in the art and can be used as host cells in which to express recombinant antibodies of the invention to thereby produce an antibody with altered glycosylation. For example, cell lines Ms704, Ms705, and Ms709 lack the fucosyltransferase gene, FOTS (alpha (1,6) fucosyltransferase), so antibodies expressed in cell lines Ms704, Ms705, and Ms709 lack fucose in your carbohydrates. The Ms704, Ms705, and Ms709 FOTS- / - cell lines were created by targeted disruption of the FOT8 gene in CH0 / DG44 cells using two replacement vectors (see, for example, US Patent Publication No. 2004 / 0110704 or Yamane- Ohnuki, et al., Siotechnol.Eioeng., 2004, 87, 614-622). As another example, European Patent No·. EP 1, 176, 195 describes a cell line with a functionally altered FOT8 gene. which encodes a fucosyl transferase, so that the antibodies expressed in such a cell line present hypofucosylation reducing or eliminating the enzyme related to the alpha 1,6 bond, and also describe cell lines which have a low enzymatic activity to add fucose to the N -acetylglucosamine that binds to the Fc region of the antibody or does not have the enzymatic activity, for example, the rat myeloma cell line. YB2 / 0 (ATCC CRL 1662). International Patent Publication WO 03 / 035835 describes a CHO cell line variant, Lee 13 cells, with reduced ability to bind fucose to Asn(.297)-linked carbohydrates, also resulting in hypofucosylation of antibodies expressed on such host cell ( see also Shields, et al., J. Biol. Chem. (e.g., beta(1,4)-N-acetylglucosatninyltransferase III (GnTIII)) such that antibodies expressed in the engineered cell lines exhibit increased bisenting GlcNac structures resulting in increased ADCC activity of the antibodies ( see also Umana, et al., Nat < Biotech. 1999, 77, 176-180). Alternatively, the fucose residues of the antibody can be cleaved using a fucosidase enzyme. For example, l a Fucosidase alpha-L~ fucos idas-a removes fucosyl residues from antibodies as described in Tarentino, et al., Biochem. 1975, 14, 5516-5523. "Pegylation" refers to a modified antibody, or a fragment thereof, that is typically reacted with polyethylene glycol (PEG), such as a reactive ester or aldehyde derivative of PEG, under conditions in which one or more PEG groups become attached to the antibody or antibody fragment. The pegylation. it can, for example, increase the biological (eg, serum) half-life of the antibody. Preferably, the pegylation is carried out by an acylation reaction.or an alkylation reaction with a reactive PEG molecule (or analogous reactive water-soluble polymer). As 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 monoalkyl(Ci-Cid- or ar.yloxy-poly ethylene glycol or polyethylene glycol-maleimide The antibody to be pegylated may be an aglycosylated antibody Methods for pegylation are known in the art and can be applied to the antibodies of the invention, as described, for example, in the European Patent Nos. EP 0154316 and EP 0401384 and US Patent No. 5,824,778, the disclosures of each of which are incorporated by reference herein The terms "fusion protein" or "fusion polypeptide" refer to proteins that combine the properties of two or more individual proteins Such proteins have at least two heterologous polypeptides covalently linked either directly or via an amino acid linker The polypeptides that make up the protein fusion are typically C-terminal or N-terminal ligated, although they may also be C-terminal to C-terminal ligated, N-terminal to N-terminal, or N-terminal to C-terminal. The polypeptides of the fusion protein may be in any order and may include more than one of either or both of the constituent polypeptides. The term encompasses conservatively modified variants, polymorphic variants, . alleles, mutants, subsequences, interspecies homologues, and immunogenic fragments of the antigens that constitute the fusion protein. The fusion proteins of the disclosure may also comprise additional copies of a component antigen or immunogenic fragment thereof. The fusion protein may contain one or more binding domains linked together and further linked to an Fc domain, such as an Fc domain of IgG. Fusion proteins can further be ligated together to mimic a monoclonal antibody and provide six or more binding domains. Fusion proteins can be produced by recombinant methods as is known in the art. The preparation of fusion proteins is known in the art and is described, for example, in International Patent Application Publication Nos. WO 1995 / 0277.35 Al, WO 2005 / 103077 Al, WO 2-008 / 025516 Al, WO 2009 / 007120 Al, WO 2010 / 00'3766 Al, WO 2010 / 010051 Al, WO 2010 / 078966 Al, US Patent Application Publication Nos. US 2015 / 0125419 Al and US 2016 / 0272695 Al, and US Patent No. 8,921,519 , the descriptions of each of which are incorporated by reference herein. The term "heterologous" when used with reference to portions of a nucleic acid or protein indicates that the nucleic acid or protein comprises two or more subsequences that are not found in the same relationship to each other in nature. For example, nucleic acid is typically recombinantly produced, having two or more sequences from unrelated genes arranged to constitute a new functional nucleic acid, for example, a promoter from one source and a coding region from another source, or coding regions from different sources. Similarly, one. "heterologous protein" means that the protein comprises two or more subsequences that are not found in the same relationship to each other in nature. Similarly, a heterologous protein indicates that the protein comprises two or more subsequences that are not found in the same relationship to one another in nature (eg, a fusion protein). The term "conservative amino acid substitutions" means amino acid sequence modifications which do not abrogate binding of an antibody or fusion protein to antigen. Conservative amino acid substitutions include the substitution of an amino acid in a class for an amino acid from the same class, where a class is defined by common physicochemical amino acid side-chain properties and high substitution frequencies in homologous proteins found in nature, as shown. determined, for example, by a standard Dayhoff frequency ambience swap matrix or BLOSU14 matrix. Six general classes of amino acid side chains have been categorized and include: Class I (Cys), Class II (Ser, Thr, Pro,.Wing, Qly) ; Class III (Asn, Asp, Gln, Glu) ; Class IV (His, Arg, Lys) ; Class V (.He, Leu, Val, Met) ; and Class VI (Phe, Tyr, Tip). For example, substitution of an Asp for another class III residue such as Asn, Gln, or Glu, is a conservative substitution. Thus, a predicted nonessential amino acid residue in an antibody is preferably replaced with another amino acid residue of the same kind. Methods for identifying conservative amino acid substitutions which do not eliminate antigen binding are well known in the art (see, for example, Brummell, et al., Biochemistry 1993, 32, 1180-1187; Kobayashi, et al., Protein Eng 1999, 12, 879-884 (1999) and Burks, et al., Proa Nati Acad, Sci USA 1997, 94, 412-417 The terms "'sequence identity", "percent identity " and "percent sequence identity" (or synonyms thereof, eg, "99% identical") in the context of two or more nucleic acids or polypeptides, refers to two or more sequences or subsequences that are the same or that have a specified percentage of nucleotide or amino acid residues that are the same, when compared and aligned (introducing gaps, if necessary) for maximum correspondence, not considering any conservative amino acid substitutions as part of sequence identity Percent identity can be measured using do sequence comparison software or algorithms or by visual inspection. Various algorithms and software are known in the art that can be used to obtain nucleotide or amino acid sequence alignments. Suitable programs for determining percent sequence identity include, for example, the BLAST suite of programs available from the US Government National Center for Biotechnology Information BLAST website. Comparisons between two sequences can be carried out using either the BLASTN or BLASTP algorithm. The BLASTN is used to compare nucleic acid sequences, while the BLASTP is used to compare amino acid sequences. ALIGN, ALIGN-2 (Genentech, South San Francisco, California) or MegAlign, -available from DNASTAR, are additional publicly available software programs that can be used to align sequences. One of skill in the art can determine appropriate parameters for maximum alignment by particular alignment software. In certain embodiments, the fault parameters of the alignment software are used. As used herein, the term "variant" encompasses but is not limited to antibodies or fusion proteins which comprise an amino acid sequence which differs from the amino acid sequence of a reference antibody or by one or more substitutions, deletions and / or additions at certain positions within or adjacent to the amino acid sequence of the reference antibody. The variant may comprise one or more conservative substitutions in its amino acid sequence compared to the amino acid sequence of a reference antibody. Conservative substitutions may involve, for example, the substitution of similarly charged or uncharged amino acids. The variant retains the ability to specifically bind to the antigen of the reference antibody. The term "variant" also includes antibodies or pegylated proteins. Nucleic acid sequences implicitly encompass conservatively modified variants thereof (eg, degenerate codon substitutions) and complementary sequences, as well as the explicitly indicated sequence. Specifically, degenerate codon substitutions can be achieved by generating sequences in which the third position of -one or more selected (or all) codons is replaced with deoxyinosine and / or mixed base residues. Batzer, et al., Nucleia Ac.id.Res. 1991, '19, 5081; Ohtsuka, et al., J. Biol. Chem. 1985, 2é'Q, 2605"2$08; Rossolini, et al., Mol. Cell. Probes 1994, 8, 91--98. The term nucleic acid is used interchangeably with cDNA, mRNA, oligonucleotide, and polynucleotide. The term "bio.similar" means a biological product, including a monoclonal antibody or protein, that is highly similar to a reference biological product authorized by the United States despite minor differences in clinically inactive components, and for which no clinically significant differences exist. significant differences between the biological product and the reference product in terms of the safety, purity, and potency of the product In addition, a similar biological or "biosimilar" medicine is a biological medicine that is similar to another biological medicine that has already been authorized for use by the European Medicines Agency. The term "tolos imi 1-ar" is also used synonymously by other regional and national regulatory agencies. Biological products or biological medicines are medicines that are manufactured by, or derived from, a biological source , such as a bacterium or yeast.They may consist of relatively small molecules such as human insulin or erythroppyetin, or complex molecules such as thionoclonal antibodies. For example, if the IL-2 reference protein is aldesleukin (PROLEUCIN), a protein approved by drug regulatory authorities with reference to aldesleukin is a "biosimilar to", aldesleukin or is a "biosimilar thereof to aldesleukin. In Europe , a similar biological or "biosimilar" medicine is a biological medicine that is similar to another biological medicine that has already been authorized for use by the European Medicines Agency (EMA).The relevant legal basis for similar biological applications in Europe is the Article 6 of Regulation (EC) No 726 / 2004 and Article 10(4) of Directive 2001 / 83 / EC, as amended, and therefore in Europe, the biosimilar may be authorized, approved for authorization or subject to an application for authorization under Article 6 of Regulation (EC) No 726 / 2004 and Article 10(4) of Directive 2001 / 83 / EC The original biological medicinal product already authorized may be referred to as a ''medicinal product of reference" and n Europe. Some of the requirements for a product to be considered a biosimilar are outlined in the CUMP Guidelines on Similar Biological Medicinal Products. In addition, product-specific guidelines, including guidelines that relate to monoclonal antibody biosimilars, are provided on a product-by-product basis by the EMA and posted on its website. A biosimilar as described herein may be similar to the reference medicinal product through quality characteristics, biological activity, mechanism of action, safety and / or efficacy profiles. In addition, the biosimilar may be used or proposed for use to treat the same conditions as the reference medicinal product. In this way, a biosimilar - as described in 1.a herein - can be considered to have similar or highly similar quality characteristics to a reference medicinal product. Alternatively, or in addition to, a biosimilar as described herein may be considered to have similar or highly similar biological activity to a reference medicinal product. Alternatively, or in addition to, a biosimilar as described herein may be considered to have a similar or highly similar safety profile to a reference medicinal product. As described herein, a biosimilar in Europe is compared to a reference medicinal product which has been authorized by the EMA. However, in some cases, the biosimilar may be compared to a biological medicinal product which has been authorized outside the European Economic Area (a "comparator" not authorized by the EEA) in certain studies. Such studies include, for example, certain clinical and non-clinical in vivo studies. As used herein, the term "biosimilar" also refers to a biological medicinal product which has been or may be compared to a comparator not authorized by the EEA. Certain biosimilars are proteins such as antibodies, antibody fragments (eg, antigen-binding moieties), and fusion proteins.A protein biosimilar may have an amino acid sequence that has minor modifications in amino acid structure (including, for example, amino acid deletions, additions, and / or substitutions), which do not significantly affect the function of the polypeptide. The biosimilar may comprise an amino acid sequence that has 97% or greater sequence identity to the amino acid sequence of its reference medicinal product, eg, 97%, 98%, 99%, or 100%. The biosimilar may comprise one or more post-translational modifications i onal is, for example, but not limited to, glycosylation, oxidation, deamidation, and / or truncation which is / are different from the post-translational modifications of the medicinal product provided that the differences do not result in a change in the safety and / or efficacy of the medicinal product. The biosimilar may have a different or identical glycosylation pattern to the reference medicinal product. Particularly, though not exclusively, the biosimilar may have a different glycosylation pattern if the differences address or are intended to address safety concerns associated with the reference medicinal product. Additionally, the biosimilar may deviate from the reference medicinal product in, for example, its strength, pharmaceutical form, formulation, excipients and / or presentation, provided that the safety and efficacy of the. medicinal product is not compromised, The biosimilar may comprise differences in e.g. pharmacokinetic (PK) and / or pharmacodynamic (PD) profiles compared to the reference medicinal product but is still considered sufficiently similar to the reference medicinal product to be authorized or considered suitable for authorization. In certain circumstances, the biosimilar presents different binding characteristics compared to the reference medicinal product, where the different binding characteristics are considered by a Regulatory Authority such as the EMA not to be a barrier for authorization as a Similar biological product. The term "biosimilar" is also used synonymously by other national and regional regulatory agencies. The term "hematologic malignancy" refers to mammalian cancers and tumors of the hematopoietic and lymphatic tissues, including, but not limited to, tissues of the blood, bone marrow, lymph nodes, and lymphatic system. Hematological neoplasms can result in the formation of a '"liquid tumor". Hematologic malignancies include, but are not limited to, acute lymphoblastic leukemia (ALL), chronic lymphocytic lymphoma (CLL), small lymphocytic lymphoma (SLL), acute myeloid leukemia (AML), acute myelogenous leukemia (CML) , acute monocytic leukemia (AMoL), Hodgkin's lymphoma, and non-Hodgkin's lymphomas. The term "B-cell hematologic neoplasm" refers to hematologic neoplasms that affect B cells. The term "liquid tumor" refers to an abnormal mass of cells that is fluid in nature. Liquid tumor cancers include, but are not limited to, leukemias, myelomas, and lymphomas, as well as other hematologic malignancies. TILs obtained from liquid tumors, which include bone marrow-resident liquid tumors, may also be referred to herein as marrow infiltrating lymphocytes (MILs). TILs obtained from liquid tumors, which include liquid tumors circulating in peripheral blood, may also be referred to herein as PBLs. The terms MIL, TIL, and PBL are used interchangeably herein and differ only based on. the type of tissue from which the cells are derived. The term "biopsy" refers to any medical procedure to obtain cancer cells, including bone marrow biopsy. The terms "acute myeloid leukemia" or "AML" refer to cancers of the myeloid blood cell lines, which are also known in the art as myelogenous leukemia and acute non-lymphocytic leukemia. Although AML is a liquid tumor, some manifestations of AML, including extramedullary manifestations such as chloroma, exhibit properties of a solid tumor, but are classified herein as a liquid tumor.The term "microenvironment", as used herein, may refer to the hematologic or solid tumor microenvironment as a whole or to an individual subset of cells within the microenvironment. The tumor microenvironment, as used herein, refers to a complex mixture of "cells, soluble factors, signaling molecules, extracellular matrices, and mechanistic signals that promote neoplastic transformation, support tumor growth, and invasion, they protect the tumor from host immunity, foster therapeutic resistance, and provide niches for dominant metastases to thrive", as described in Swartz, et al. Cancer Res., 2012, 72, 2473. Although tumors express antigens that must be recognized by T cells, clearance of the tumor by the e-1 immune system is rare due to immune suppression by the microenvironment. The term "effective amount" or "therapeutically effective amount" refers to such an amount of a compound or combination of compounds as described herein that is sufficient to effect the proposed application which includes, but is not limited to, treatment of illness. A therapeutically effective amount may vary depending on the intended application (in vitro or in vivo), or the subject and disease condition to be treated (eg, the weight, age, and gender of the subject), the severity of the condition of the disease, or the manner of administration. The term also applies to a dose that will induce a particular response in target cells (eg, reduction of platelet adhesion and / or cell migration). The specific dose will vary depending on the particular compounds chosen, the dosage regimen to be followed, whether the compound is administered in combination with other compounds, timing of administration, the tissue to which it is administered, and the. physical delivery system in which the compound is carried. A "therapeutic effect" as such term is used herein, encompasses a therapeutic benefit and / or a prophylactic benefit. A prophylactic effect includes delaying or eliminating the onset of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, reducing, hindering, or reversing the progress of a disease or condition, or any combination thereof. The terms "treatment", "treating", "treating", and the like, refer to obtaining a desired pharmacological and / or physiological effect. The effect may be prophylactic in terms of completely or partially preventing a disease or symptom thereof and / or it may be therapeutic in terms of a partial or complete cure for a disease and / or adverse effect attributable to the disease. "Treatment" as used herein, covers any treatment, of a disease- in a mammal, particularly: in a human, and includes: (a) preventing the disease from occurring in a subject which may be predisposed to the disease but has not yet been diagnosed as having it; (b) inhibit the disease, ie stop its development or progress; and (c) alleviating the disease, ie, causing regression of the disease and / or alleviating one or more symptoms of the disease. "Treatment" too. means encompass supplying an agent for the purpose. to provide a pharmacological effect, even in the absence of a disease or condition. For example, "treatment" encompasses provision of a composition that can elicit an immune response or confer immunity in the absence of a disease condition, eg, in. the case of a vaccine. The terms "QD," "qd," or- "q.d." means every day, once a day, or once a day. The terms "BID," "bid," or "b.i.d." .mean two a day, twice a day, or twice a day . The terms "TID.," "tid," or-"t.i.d." they mean three a day, three times a day, or three times daily. The terms "QID," "qid,·" or "q.i.d." they mean four a day, four times a day, or four times daily. By "tumor infiltrating lymphocytes" or "TILs" herein is meant a population of cells originally obtained as white blood cells that have left a subject's bloodstream and migrated into a tumor. TILs include, but are not limited to, CD8 + cytotoxic T cells (lymphocytes), CD4 + Thl and Thl 7 T cells, natural killer cells, dendritic cells and MI macrophages.TILs include both primary and secondary TILs. "Primary TILs" are those that are obtained from patient tissue samples as outlined herein (sometimes referred to as "freshly harvested"), and "secondary TILs" are any of the TIL cell populations that have been been expanded or proliferated as discussed herein, including, but not limited to volume TILs, expanded TILs ("REP TILs"), as well as reREP" TILs as discussed herein. TILs may in Generally, be defined either biochemically, using cell surface markers, or functionally, by their ability to infiltrate tumors and effect treatment.TILs can be broadly categorized as expressing one or more of the following biomarkers: CD4 , CD8, TCR αβ, CD27, CD28, CD56, CCR7, CD45Ra, CD95, PD-1, and CD2S Additionally and alternatively, TILs can be functionally defined by their ability to infiltrate solid tumors after reintroduction into a patient. TILs can further be categorized by potency—for example, TILS can be considered potent if, for example, interferon (IFN) release is greater than about 50 pg / mL, greater than about 100 pg / mL, greater than about 150 pg / mL, or greater than about 200 pg / mL. By "cryopreserved TILs" (or cryopreserved MILs or PBLs) as used herein, it is meant that the TILs, whether primary, bulk, or expanded (REP TILs), are treated and stored in the range of about -150°C to -gO°C. General methods for cryopreservation are also described elsewhere herein, including in the Examples. For clarity, "cryopreserved TILs" indistinguishable from frozen tissue samples which can be used as a source of Primary TILS By "thawed cryopreserved TILs" (or thawed MILs or PBLs), as used herein means a population of TILs that was previously cryopreserved and then treated to return to room temperature or higher, including but not limited to temperatures of cell culture or temperatures at which TILs can be administered to a patient By "cell population" (which includes TILs) as used herein, it means a number of cells that share common traits. In general, populations generally range from 1 X 105 to 1 X 1Q:IO in number, with different populations of TILs comprising different numbers. For example, initial growth of primary TILs in the presence of IL-2 results in a population of TILs of approximately 1x volume. 108 cells. REP expansion is generally done to provide stocks of. 1.5 x 103 up to 1.5 x LO10 cells for infusion. In general, TILs are initially obtained from a sample. of the patient's tumor ("primary TILs") and then expanded to a larger population for further manipulation as described herein, optionally cryopreserved, restimulated as outlined herein, and optionally evaluated for phenotype and metabolic parameters such as a TIL health indication. In general, the harvested cell suspension is called a "primary cell population" or a "freshly harvested" cell population. In general, as discussed herein, TILs are initially prepared by obtaining a primary population of TILs from a patient's resected tumor as discussed herein (the "primary cell population" or "first cell population"). ). This is followed with an initial volume expansion using a culture of the cells with I.L-2, - forming a second population of cells (sometimes referred to herein as "volume TIL population" or "second population"). The term "cytotoxic lymphocyte" includes cytotoxic T cells (CTL) (including CD8* cytotoxic T lymphocytes and CD4* T-helper cells), natural killer T cells (NKT), and natural killer (NK) cells. Cytotoxic lymphocytes may include, for example, peripheral blood-derived TCR γδ-positive or TCR αβ-positive T cells activated by tumor-associated antigens and / or transduced with tumor-specific chimeric antigen receptors- or T-cell receptors, and tumor infiltrating lymphocytes (TILs).The term "central memory T cells" refers to a subset of T cells that, in humans, are CD45.RO+ and constitutively express CCR.7 (CCR7h i) and CD62L (CD62 hi). The central memory T cell surface phenotype also includes TCR, CD3, CD 127 (IL-7R), and IL-15R. Transcription factors for central memory T cells include BCL-6, BCL-6B, MBD.2, and ΒΜΙΣ. Central memory T cells mainly secrete IL-2 and CD40.L as effector molecules after TCR activation. Central memory T cells are predominant in the CD4 compartment. blood, and in humans they are proportionally enriched in lymph nodes and tonsils. The term "effector memory T cells" refers to a subset of mammalian or human T cells that, like those. Central memory T cells are CD45R0+, but have lost constitutive expression of CCR7 (CCR71o) and are heterogeneous or low for expression of CD62L (CD62Llo). The central memory T cell surface phenotype also includes TCR, CD.3, CD 127 (IL-7R), and IL-15R. Transcription factors for central memory T cells include BLI.MP1. Effector memory T cells rapidly secrete high levels of inflammatory cytokines after antigenic stimulation, including interferon-γ, IL-4, and IL-5. Effector memory T cells are predominantly in the CD8 compartment in the blood, and in humans they are proportionally enriched in the lung, liver, and intestine. effector memory T cells. CD8+ cells carry large amounts of perforin. The term "closed system" refers to a system which is closed in the external environment. Any closed system suitable for cell culture methods can be employed with the methods of the present invention. Closed systems include, for example, but are not limited to closed G containers. Once a tumor segment is added to the closed system, the system is not opened to the outside environment until the TILs are ready to be administered to the patient. In some embodiments, the methods of the present disclosure further include, a "pre-REP*" step in which tumor tissue or cells from tumor tissue are grown in standard laboratory medium (including without limitation RPMI) and are treated with reagents such as irradiated feeder cells and anti-CD3 antibodies to achieve a desired effect, such as an increase in the number of TILs and / or an enrichment of the population for cells containing desired cell surface markers or other functional or biochemical, structural characteristics The pre-REP stage can use laboratory-grade reagents (under the assumption that laboratory-grade reagents are diluted during or after a REP stage.), making it easier to incorporate alternative strategies to improve production of TIL Therefore, in some embodiments, the described TLR agonist and / or peptide or peptidomimetics may be included in the cultured during the pre-REP stage, If cultured pre-REP may, in some embodiments, include IL-2. The present invention is directed in preferred aspects to new methods for augmenting REPs with one or more additional restimulation protocols, also referred to herein as a "rapid expansion restimulation protocol" or "reREP", which surprisingly leads to subsets of T cells from. expanded memory, including the effector memory T-cell subset, and / or enhancement of glidolytic respiration signatures—compared with freshly harvested TILs or thawed cryopreserved TILs to restimulated TILs (sometimes referred to herein as "reTILs"). "). That is, by using a reREP procedure on cryopreserved TILs, patients can receive healthy, highly metabolically active TILs, leading to more favorable outcomes. When "an anti-tumor effective amount", "a tumor-inhibiting effective amount", or "therapeutic amount" is indicated, the precise amount of the compositions of the present invention to be administered can be determined by a specialist with consideration. of individual differences, in age, weight, size of the tumor, extension of the infection or metastasis, and condition of the patient (subject).It can be stated in general, that a pharmaceutical composition comprising the genetically modified cytotoxic lymphocytes described herein, can be administered at a dosage of LO4 up to 10'-; cells / kg body weight (eg, 10" to ΙΟ6, 105 to 1Q10·, 10s to 1011, 106 to 1.01G, 106 to 10"·, 1.07 to 10n, 107 to 1Ώ10, 10® to 10::; , 10® up to 10ls, 10" up to 1021, or 10® up to 10i0 cells / kg body weight)', which includes all integer values ​​within these ranges. Genetically modified toxic cyto-lymphocyte compositions may also be administered multiple times at these dosages.The genetically modified cytotoxic lymphocytes can be administered using infusion techniques that are commonly known in immunotherapy (see, eg, Rosenberg et al., New Eng. J. of Mea. 319:1676, 1988). The optimal dosage and dosage regimen for a particular patient can be readily determined by one skilled in the art of medicine by monitoring the patient for signs of disease and adjusting treatment accordingly For the avoidance of doubt, it is intended herein that character particular characteristics- (for example, integers, characteristics, values, uses, diseases, formulas, compounds or groups) described in conjunction with a particular aspect, modality or example of the invention, are understood to be applicable to any other aspect, modality or example described herein, unless inconsistent therewith. Thus, such features may be used where appropriate, in conjunction with any of the definitions, claims, or embodiments defined herein. All features described in this description (including any of the claims, abstract, and accompanying drawings), and / or all steps of any method or process so described, may be combined in any combination, except combinations where at least some of the characteristics and / or stages are mutually exclusive. The invention is not restricted to certain details of any of the described embodiments. The invention extends to any new or novel combination of the features described in this description (including any of the claims, abstract and accompanying drawings), or to any new or novel combination of the steps of any method or process so described. The terms "about" and "approximately" mean within a statistically significant range of a value. Such a range may be within any order of magnitude, preferably within 50%, more preferably within 20%, still more preferably within 10%, and even more preferably within 5% of a given value or range. The allowable variation encompassed by the terms "about" or "approximately" depends on the particular system under study, and can be readily appreciated by one of ordinary skill in the art. However, as used herein, the terms "about" and "approximately" mean that dimensions, sizes, formulations, parameters, shapes, and other quantities and characteristics are not and need not be exact, but may be approximate. - and / or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding, measurement error and the like, and other factors known to those of skill in the art. In general, a dimension, size, formulation, parameter, shape, or other quantity or characteristic is "about" or "approximate" whether or not it is expressly stated to be such. It is indicated that modalities of very different sizes, shapes and dimensions can employ the described arrangements. The transitional terms "comprising", "consisting essentially of", and "consisting of", when used in the appended claims, in original and amended form, define the scope of the claim with respect to that unmentioned additional-claimed elements or steps, if any, are excluded from the scope of the claim(s). The term "comprising" is intended to be inclusive or open-ended and does not exclude any additional, unmentioned items, methods, steps or materials.The term "consisting of" excludes any element, step or material other than those specified in the claim and, in the. latter case, ordinary impurities associated with the specified material(s). The term "consisting essentially of" limits the scope of a claim to the elements, steps, or material(s) specified, and those that do not materially affect the basic and novel feature(s) of the claimed invention. All compositions, methods, and kits described herein employing the present invention may, in altered embodiments, be more specifically defined by any of the transition terms "comprising", "consisting essentially of", and "consisting of". 'Modalities- of Methods to Expand Therapeutic T Cells Including Peripheral Blood (PBLs) and / or Bone Marrow (MILs) PBL Method 1, In one embodiment of the invention, PBLs are expanded using the processes described herein. In one embodiment of the invention, the method comprises obtaining a PBMC sample from whole blood. In one embodiment, the method comprises enriching for T cells by isolating pure T cells from PBMCs using negative selection of a non-CD19+ fraction. On day 0, pure T cells were cultured with anti-CD3 / 'anti-CD28 antibodies (DynaBeads®) in a 1:1 ratio (beads:cells) and IL-2 at 3000 IU / ml. On day 4, additional IL-2 is added to the culture at 3000 IU / ml. On day 7, the culture is again stimulated with anti-CD3 / anti-CD28 antibodies (DynaBeads®) in a 1:1 ratio (beads:cells), and additional IL-2 at 3000 IU / ml is added to it. culture.. The PBLs are harvested on day 14, the beads are removed, and the PBLs are sung and phenotyped. In one embodiment, the method comprises enriching T cells by isolating pure T cells from PBMCs using magnetic bead-based negative selection of a non-CD19+ stock. In one embodiment of the invention, PBL Method 1 is performed as follows: On day 0, a crypreserved PBMC sample is thawed and PBMCs are counted. T cells are isolated using Pan Human T Cell Isolation Kit and LS columns (Miltenyi Biotec'). Isolated T cells are counted and plated at 5x10® cells per well of a 24-well GRex plate and co-cultured with DynaBeads® (anti-CD3 / anti-CD28) at a 1:1 ratio with IL-2 at 3000 lU / ml in a total of 8ml of CM2 medium per well. On day 4, the medium in each well is exchanged from CM2 to AIM-V with fresh IL-2 at 3000 IU / ml. On day 7, expanded cells are harvested, counted > then grown at 15x10® cells per flask in GRex I0M flasks with IL-2 at 3000 IU / ml and DynaBeads"1, at a 1:1 ratio (beads:cells). ) in a total of 100 ml of AIM-V medium. On day 11, the medium is exchanged to CM-4 medium supplemented with fresh IL-2 at 3000 IU / ml. On day 14, the DynaBeads® are removed using a DynaMag Magnet (DynaMag"i,-1.5) and the cells are counted. In one embodiment of the invention, PBL Method 1 is performed as follows: On day 0, a cryopreserved PBMC sample is thawed and the PBMCs are sung. T cells are isolated using Pan Human T Cell Isolation Kit and LS columns (Milt.en.yi Biotec). Isolated T cells are counted and seeded into a 5x10-cell per well 24-well GRex plate and co-cultured with DynaBeads' (anti-CD3 / 'anti-CD28) at a ratio. 1:1 with IL-2 at 3000 IU / mL in a total of 8 mL of CM2 Raedlo. per cavity. On day 4, the medium in each well is exchanged from CM2 to AIM-V with fresh IL-2 at 3000 LU / ml. On day 7, PBLs are harvested, counted, then reseeded at 1xIQs cells per well of a new GRex-24 well plate with IL-2 at 3000 IU / ml and DynaBeads® at a 1:1 ratio (beads:cells). in a total of 8ml of AIM-V medium. In the. day 11, the medium is exchanged to CM-4 medium supplemented with fresh IL-2 at 3000 IU / ml. On day 1.4, the DynaBeads® are removed using a DynaMag Magnet (DynaMag^-lS) and the cells are counted. PBL Method 2. In one embodiment of the invention, PBLs are expanded using PBL Method 2, which comprises obtaining a PBMC sample from whole blood. T cells from PBMCs are enriched by incubating the PBMCs for at least three hours at 37°C and then isolating non-adherent cells·. Non-adherent cells are those expanded similarly with PBL Method 1, ie, on day 0, non-adherent cells are cultured with anti-CD3 / anti-CD28 antibodies (DynaBeads®) in one. 1:1 ratio (beads-.cells) and IL-2 at 3000 IU / ml. On day 4, additional IL-2 is added to the culture at 3000 IU / mL. On day 7, the culture is again stimulated with anti-CD3 / anti-CD28 antibodies (DynaBeads'®} in a 1:1 ratio (beads to cells), and additional IL-2 at 3000 IU / ml is added to the culture. PBLs are harvested in on day 14, the beads are removed, and the PBLs are counted and phenotyped In one embodiment of the invention, PBL Method 2 is performed as follows: On day 0, the cryopreserved PBMC sample is thawed and the PBMC cells are seeded at 5 million cells per well in a 6-well plate in CM--2 medium and incubated for 3 hours at 3 7 degrees Celsius After 3 hours, the non-adherent cells, which are the PBLs, are removed and PBLs are cultured with anti-CD3 / anti-CD28 DynaBeads"·'' at a 1:1 bead:cell ratio, at IxlO6 cells per well and IL-2 at 3000 IU / ml in a total of 7ml in CM-2 medium In each well FROM a 24-well GRex plate On day 4, the medium in each well is exchanged with AI'M-'V and I medium fresh L-2 at 3000 IU / ml. On day 7, expanded cells are harvested, counted, then cultured at 15x106 cells per flask in GRex ION flasks with IL-2 at 3Ό0Ό lU / ml and DynaBeads*' at a 1:1 ratio. pearls) in a total of 100 ml of AIM-V medium. On day 11, the medium is changed to CM-4 medium and supplemented with fresh IL-2 (3000 IU / ml). On day 14, the DynaBeads are removed using a DynaMag™ Magnet (DynaMag™-15) and the cells are counted. In one embodiment of the 1st invention, PBL Method 2 is performed as follows: On day 0, the cryopreserved PBMC sample is thawed and PBMC cells are seeded at 6 million cells per well in. a 6-well plate in CM-2 medium and incubated for 3 hours at 37 degrees Celsius. After 3 hours, the non-adherent cells, which are the PBLs, are removed and counted. PBLs are cultured with anti-CD3 / anti-CD28 DynaBeads* in a 1:..1 bead:-cell ratio, at .1x106 cells per well and IL-2 at 3000 IU / mL in a total of 7 mL. in CM-2 medium in each well of a 24-well GRex plate. On day 4, the medium in each well is exchanged with AIM-V medium and fresh IL-2 at 3000 IU / ml. On day 7, the expanded cells are harvested, counted, then cultured at 1x10® cells per well in a new 24-well GRex plate with IL-2 at 3000 Ιϋ / ml and DynaBeads® at a 1:1 ratio (T- cells:pearls)- in a total of 8ml of AIM-V medium. On day 1.1, the medium is changed to CM-4 medium and supplemented with fresh IL-2 (3000 lü / ml). On day 14, the DynaBeads are removed using a DynaMag™ Magnet (DynaMagn'~15) and the cells are counted. PBL Method 3.In one embodiment of the invention, PBLs are expanded using PBL Method 3, which comprises obtaining a sample of PBMC from peripheral blood. B-cells are isolated using CD19+ selection and T-cells are selected using negative selection of the non-CD19+ fraction. the PBMC sample. On day 0, T-cells and B-cells are co-cultured with anti-iCD3 / anti-CD28 antibodies (DynaBeads®) in a 1:1 ratio (beads:cells) and IL-2 at 3000 IU / ml. On day 4, additional IL-2 is added to the culture at 3000 rU / ml. On day 7, the culture is further stimulated with anti-CD3: / 'ant'iCD.2-8 antibodies (DynaBeads®) in a 1:1 ratio (beads:cells), and additional IL-2 at 30Q0 IU / ml is administered. add to the crop. PBLs are harvested on day 14, beads are removed, and PBLs are counted and phenotyped. In one embodiment of the invention, PBL Method 3 is performed as follows: On day Q, cryopreserved PBMCs derived from peripheral blood are thawed and counted. CD19+- B cells are sorted using a CD19 Multisorting Kit, Human (Miltenyi Biotec). From the non-CD19+ cell fraction, T cells are purified using Pan Human T-Cell Isolation Kit and LS columns (Miltenyi Biotec). T-cells (PBLs) and B-cells are co-cultured at different ratios in a 24-well GRex plate in approximately 8 ml of CM2 medium in the presence of IL-2. at approximately 3000IU / 'ml. The B-cell:T-cell ratios are 0.1:1,- 1:1, and 10:1. The T-cell / B-cell co-culture is stimulated with anti-CD3 / anti-CD28 antibodies (DynaBeads®) in a 1:1 ratio (beads; cells). On day 4, the medium is exchanged from CM2 to . AI.M.-V medium and additional IL-2 is added to the culture at 3000 IU / ml. On day 7, cells are harvested and counted and re-plated in a new 24-well Grex plate in AIM-V medium. at a cell range from approximately 1.ExlO5 to approximately 4xl0s cells per well and stimulated with anti-CD3 / anti-CD2-8 antibodies (.DynaBeads®) in a 1:1 ratio (beads:cells), with additional IL-2 at 3000 IU / ml. On day 14, the DynaBeads are removed using a DynaMag'* Magnet (DynaMag™-1.5) and the cells are counted. In a. In this embodiment, PBMCs are isolated from a whole blood sample. In one embodiment, the PBMC sample is used as the starting material to expand the PBLs. In one embodiment, the sample is cryopreserved prior to the expansion process. In another embodiment, a fresh sample is used as the starting material to expand the PBLs. In one embodiment of the invention, T cells are isolated from PBMCs using methods known in the art. In. In one embodiment, T cells are isolated, using a Pan Human T Cell Isolation Kit and LS columns. In one embodiment of the invention, T cells are isolated from PBMCs using art-known antibody selection methods, eg, CD19 negative selection. In one embodiment of the invention, the. process is carried out for about 7 days, about 8 days, about 9 days, about 10 days, about 11 days, about 12 days, about 13 days, or about 14 days. In another embodiment, the process is carried out for approximately 7 days. In another embodiment, the process is carried out for approximately 14 days. In one embodiment of the invention, PBMCs are cultured with anti-CD3 / anti-CD28 antibodies. In. one embodiment, any available anti-CD3 / anti-CD28 product is useful in. the present invention. In one embodiment of the invention, the commercially available products are. .DynaBeads*. In one embodiment, the DynaBeads® are cultured with the PBMCs in a 1:1 ratio (beads:cells). In another embodiment, the antibodies are DynaBeads® cultured with the PBMCs in a ratio of 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, or 5:1. (beads: cells), In one embodiment of the invention, the steps of culturing the antibody and / or the step of restimulating cells with antibody is performed for a period of from about 2 to about 6 days, from about 3 to about 5 days, or for about 4 days. In one embodiment of the invention, the step of culturing the antibody is performed for a period of about 2 days, 3 days, 4 days, 5 days, or 6 days.In one embodiment, the PBMC sample is cultured with 'IL-2·. In a. embodiment of the invention., the cell culture medium used for expansion of PBLs from PBMCs comprises IL-2' at a concentration selected from the group consisting of approximately 100 ITJ / mL, approximately 200 ID' / mL , approximately 300 IU / mL, approximately 400 IU / mL, approximately 100 IU / mL, approximately 100 IU / mL, approximately 100 IU / mL, approximately 100 TV / mL, approximately 100 IU / mL, approximately 500 IU / mL, approximately 600 IU / mL, approximately 700 IU / mL, approximately 800 IU / mL, approximately 900 IU / mL, approximately 1,000 IU / mL, approximately 1,100 IU / mL, approximately 1,200 IU / mL, approximately 1,300 IU / mL, approximately 1,400 IU / mL, approximately 1,500 IU / mL, approximately 1,600 IU / mL, approximately 1,700 IU / mL, approximately 1,800 IU / mL, approximately 1,900 IU / mL, approximately 2,000 IU / mL, approximately 2,100 Γϋ / mL, .approximately 2,200 IU / mL, approximately 2,300 IU / mL, appro Approximately 2,400 IU / mL, approximately 2.5-00 IU / mL, approximately 2,600 IU / mL, approximately 2,700 IU / mL, approximately 2,800 IU / mL, approximately 2,900 IU / mL, approximately 3,00.0 IU / mL, approximately 3,100 IU / mL, approximately 3,20.0 IU / mL, approximately 3,300 IU / mL, approximately 3.4-00 IU / mL, approximately 3,500 IU / mL, approximately 3,600 IU / mL, approximately 3,700 IU / mL , about 3,800 IU / mL, about 3,900 IU / mL, about 4,000 IU / mL, about 4,100 IU / mL, about 4.2-00 IU / mL, about 4,300 IU / mL, about 4,400 IU / mL, about 4,500 IU / mL, approximately 4,600 IU / mL, approximately 4,700 IU / mL, approximately 4,800 IU / mL, approximately 4,900 IU / mL, approximately 5,000 IU / mL, approximately 5-,-100 IU / mL, approximately 5,200 IU / mL, approximately 5,300 IU / mL, approximately 5,400 IU / mL, approximately 5,500 IU / mL, approximately 5,600 IU / mL, approximately 5,700 IU / mL, approximate approximately 5,800 IU / mL, approximately 5,900 IU / mL, approximately 6,000 IU / mL, approximately 6,500 IU / mL, approximately 7.0:00 IU / mL, approximately 7,500 IU / mL, approximately 8,0.00 IU / mL, approximately 8,500 IU / mL, approximately 9,000 IU / mL, approximately 9,500 IU / mL, and approximately 10,000 IU / mL. In one embodiment of the invention, the number of starting cells of PBMCs for the expansion process is from about 25,000 to about 1,000,000, from about 3-0,000 to about 900,000, from about 3-5,000 to about 850,000, from about 40,000 to about 800,000, from about 45,000 to about 800,000, from about 50,000 to about 750,000, from about 5.5,000 to about 700,000, from about 60,000 to about 650,000, from about 65,000 to about 600,000, from about 70,000 to about ,550,000, preferably from about 75,000 to about 500,000, from about 80,000 to about 450,000, from about 85,000 to about 400,000, from about 90,000 to about 350,000, from about 95.0 00 to about 300,000, from about 100,000 to about 250,000, from about 105,000 to about 200,000, or from about 110,000 to about 150,000. :In one embodiment of the invention, the starting cell number of PBMCs is about 138,000, 140,000, 145,000, or more. In another embodiment, the starting cell number of PBMCs is approximately 28,000. In another embodiment, the starting cell number of PBMCs is approximately 62,000. In another embodiment, the starting cell number of PBMCs is approximately 338,000. In another embodiment, the starting cell number of PBMCs is approximately 336,000. In one embodiment of the invention, cells are grown in a 24-well GRex plate. In one embodiment of the invention, a comparable cavity plate is used. In one embodiment, the starting material for the expansion is approximately 5x10? T-cells per cavity. In one embodiment of the invention, there are IxlO6 cells per well. In one embodiment of the invention, the number of cells per well is sufficient to seed the well and expand the T cells. In one embodiment of the invention, the fold expansion of PBLs is from about 0% to about 100%, 25% to about 95%, 30% to about 90%, 35% to about 85%, 40% to about 80%. %, 45% to about 75%, 50% to about 100%, or 25% to about 75%. In one embodiment of the invention, the expansion times is about 25%. In another embodiment of the invention, the expansion times is about 50%. In another embodiment, the expansion times is about 75%. In one embodiment of the invention, additional IL-2 can be added to the culture one or more days through the process. In one embodiment of the invention, additional IL-2 is added on day 4. In one embodiment of the invention, additional IL-2 is added on day 7. In one embodiment of the invention, additional IL-2 is added on day 11. In another embodiment, additional IL-2 is added on day 4, day 7, and / or day 11. In one embodiment of the invention, the cell culture medium may be changed on one or more days to through the cell culture process. In one embodiment, the cell culture medium is changed on day 4, day 7, and / or day 11 of the run. In one embodiment of the invention, PBLs are cultured with additional IL-2 for a period of 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, or 14 days. In one embodiment of the invention, the PBLs are cultured for a period of 3 days after each addition of IL-2. In one embodiment, the cell culture medium is exchanged at least once during the method. In one embodiment, the cell culture medium is exchanged at the same time that additional IL-2 is added. In another embodiment, the cell culture medium is exchanged on at least one of day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 8, day 9, day 10, day 11, day 12 , day 13, or day 14. In one embodiment of the invention, the cell culture medium used throughout the method may be the same or different. In one embodiment of the invention, the cell culture medium is CM-2, CM-4, or AIM-V. In one embodiment of the invention, the T-cells can be restimulated with anti-CD3 / anti-CD28 antibodies on one or more days through the 14-day expansion process. In one embodiment, the T cells are restimulated on day 7. In one embodiment, 10M GR-ex flasks are used for the restimulation step. In one embodiment of the invention, comparable flasks are used. In one embodiment of the invention, the DynaBeads® are removed using a DynaMag'* Magnet, the cells are counted, and the cells are analyzed using phenotypic and functional analysis as further described in the Examples below. In one embodiment of the invention, the antibodies are separated from the PBLs or MILs using methods known in the art. In any of the above embodiments, magnetic bead-based selection of TILs, PBLs, or MILs is used. In one embodiment of the invention, the PBMC sample is incubated for a period of time at a desired effective temperature to identify non-adherent cells·. In one embodiment of the invention, the incubation time is approximately 3 hours. In one embodiment of the invention, the temperature is about 37° Celsius. The non-adherent cells are then expanded using the process described above. In one embodiment of the invention, the PBMCs are obtained from a patient who has been treated with ibrutinib or another ITK or kinase inhibitor, such ITK and kinase inhibitors are as described elsewhere herein. In one embodiment of the invention, the ITK inhibitor is a covalent ITK inhibitor that covalently and irreversibly binds ITK. In one embodiment of the invention, the ITK inhibitor is an ITK-binding allosteric ITK inhibitor. In one embodiment of the invention, PBMCs are obtained from a patient who has been treated with ibrutinib or another ITK inhibitor, including ITK inhibitors that are as described elsewhere in present 1.a, prior to obtaining a PBMC sample for use with any of the above methods, including PBL Method 1, PBL Method 2, or PBL Method 3. In one embodiment of the invention, the ITK inhibitor treatment has been administered at least 1 time, at least 2 times, or at least 3 times or more. In one embodiment of the invention, PBLs that are expanded from patients pretreated with ibrutinib or another ITK inhibitor comprise fewer LAG3+, PD-1+ cells than those expanded from patients not. pretreated with ibrutinib or another ITK inhibitor. In one embodiment of the invention PBLs that are expanded from patients pretreated with ibrutinib or another ITK inhibitor comprise increased levels of IFNγ production than those expanded from patients not pretreated with ibrutinib or another ITK inhibitor. In one embodiment of the invention, PBLs that are expanded from patients pretreated with ibrutinib or another ITK inhibitor comprise increased lytic activity at lower target-protector cell ratios than those expanded from patients not pretreated with ibrutinib or another ITK inhibitor. In one embodiment of the invention, patients pretreated with ibrutinib or another ITK inhibitor have higher expansion times compared to untreated patients. In one embodiment of the invention, the method includes a step of adding an ITK inhibitor to the cell culture. In one embodiment, the ITK inhibitor is added in. one or more of day 0, day. 1, day 2, day 3, day 4, day 5, day 6, day 7, day 8, day 9, day 10,. day 11, day 1.2, day 13, or day 14 of the process. In one embodiment, the ITK inhibitor is added on days during the method when the cell culture medium is exchanged. In one embodiment, the ITK inhibitor is added on day 0 and when the cell culture medium is exchanged. In one embodiment, the ITK inhibitor is added during the method when IL-2 is added. In one embodiment, the ITK inhibitor is added on day 0, day 4, day 7, and optionally day 1.1 of the method. In one embodiment of the invention, the ITK inhibitor is added on day 0 and day 7 of the method. In one embodiment of the invention, the ITK inhibitor is one known in. The technique. In one embodiment of the invention, the ITK inhibitor is one described elsewhere herein. In one embodiment of the invention, the ITK inhibitor is used in the method at a concentration of from about 0. In M to about 5 u M. In one embodiment, the ITK inhibitor is used in the method at a concentration of about 0.1 µM. nM, 0.5nM, 1nM, 5nM, 10nM, 20nM, 30nM, 40nM, 50nM, 60nM, 70nM, 80nM, 90nM, 100nM, 150nM, 200nM, 250nM, 300 nM, 350 nM > 400 nM, 450 nM, 500 nM, 550 nM, 600 nM, 650 nM, 700 nM, 750 nM, 800 nW, 850 nM, 900 nM, 950 nM, 1 uM, 2 uM, 3 uM , 4 uM, or 5 uM. In one embodiment of the invention, the method includes a step of adding an ITK inhibitor when the PBMCs are derived from a patient who has no prior exposure to an ITK inhibitor treatment, such as ibrutinib. In some embodiments, the PBMC sample is from a subject or patient who has been optionally pre-treated with a regimen comprising a kinase inhibitor or an ITK inhibitor. In some embodiments, the tumor sample is from a subject or patient who has been pre-treated with a regimen comprising a kinase inhibitor or an ITK inhibitor. In some embodiments, the PBMC sample is from a subject or patient who has been pre-treated with a regimen comprising a kinase inhibitor or an ITK inhibitor, has undergone treatment for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or 1 year or more. In another embodiment, the PBMCs are derived from a patient who is currently on an ITK inhibitor regimen, such as ibrutinib. In some embodiments, the PBMC sample is from a subject or patient who has been pre-treated with a regimen comprising a kinase inhibitor or an ITK inhibitor and is refractory to treatment with a kinase inhibitor or an ITK inhibitor, such as ibrutinib. In some embodiments, the PBMC sample is from a subject or patient who has been pre-treated with a regimen comprising a kinase inhibitor or an ITK inhibitor but is no longer undergoing treatment with a kinase inhibitor or a TKI inhibitor. ITK. In some embodiments, the PBMC sample is from a subject or patient who has been pre-treated with a regimen, comprising a kinase inhibitor or uh TKI inhibitor, but is no longer undergoing treatment with a kinase inhibitor or an inhibitor. of ITK and has not been subjected to. treatment for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 1 year or more. In another embodiment, PBMCs are derived from a patient who has previously been exposed to an ITK inhibitor, but has not been treated for at least 3 months, at least 6 months, at least 9 months, or at least 1 year. . In one embodiment of the invention, on day 0, cells are selected for CD19+ and sorted accordingly. In one embodiment of the invention, selection is made using antibody binding beads. In one embodiment of the invention, pure T cells are isolated at day 0 from the PBMCs. In one embodiment of the invention, on day G, 'CD19+ B cells and pure T cells are co-cultured with anti-CD3 / anti-CD28 antibodies for a minimum of 4 days. In one embodiment of the invention, on day 4, IL-2 is added to the culture. In one embodiment of the invention, on day 7, the culture is restimulated with additional anti-cn3 / anti-CD28 and IL-2 antibodies. In one embodiment of the invention, on day 14, the PBLs are harvested. In one embodiment of the invention, for patients who are not pre-treated with ibrutinib or another TKI inhibitor, 10-15-ml of buffy coat will provide approximately S.xl 0s of PBMC, which, in turn, will provide approximately 5.5 x107 of. starting cell material, and approximately 11x109 PBLs at the end of the expansion process. ® MIL· (approximately 205-fold expansion). In one embodiment of the -invention, for patients who are pre-treated with ibrutinib or another TKI inhibitor, the expansion process will provide approximately 20x10* PBLs. In one embodiment of the invention, 40.3 x 10 μS PBMCs will provide approximately 4.7 x 10 5 starting cell material, and approximately 1.6 x 10 ® PBLs - (approximately 1 / 338-fold expansion). In one embodiment of the invention, the clinical dose of PBLs useful in the present invention for patients with chronic lymphocytic leukemia (CLL) is from about 0.1x10* to about 15x1O9 PBLs, from about 0.lxlO5 to -about iSxlO5 PBLs, from about 0.12x109 to about 12x109 PBLs, from about 0.1Sx103 to about 11x10* PBLs, from about 0.2x10* to about 10x10* PBLs, from about 0.3x10* to about 9x109 PBLs, from about 0.4x10a to about 8x109 PBLs, from about 0.5x10a to about 7xlOs PBLs, from about 0.6x1 O 9 to about 6 x10a PBLs, from about 0.7x10® to about 5x10a PBLs, from about 0.8-xlQ9 to about 4x10a PBLs, from about 0.9x10a to about 3x103 PBLs , or from about lxlOs to about 2x1O3 PBLs. In any of the above embodiments, the PBMCs can be derived from a whole blood sample, by apheresis, from the buffy coat, or from another method known in the art to obtain PBMCs. Methods for Expanding Marrow Infiltrating Lymphocytes (MTLs).....from Bone Marrow Derived PBMCs MIL Method 1. In an embodiment of the invention, a method for expanding MILs from bone marrow derived PBMCs is described. bone marrow. In one embodiment of the invention, the method is carried out for 14 days. In one embodiment, the method comprises obtaining PBMCs from bone marrow and cryopreservating the PBMCs. On day 0, PBMCs are cultured with anti-CD3 / anti-CD28 antibodies (DynaBeads®) in a 1:1 ratio (beads:cells) and IL-2 at 3000 IU / ml. On day 4, additional IL-2 is added to the culture at 3000 IU / mL. On day 7, the culture is again stimulated with anti-CD3 / anti-CD28 antibodies (DynaBeads®) in a 1:1 ratio (beads / cells), and additional IL-2 at 3000 IU / ml is added to the culture. MILS are harvested on day 14, beads are removed, and MILs are optionally counted and phenotyped. In one embodiment of the invention, MIL Method 1 is performed as follows: On day 0, a sample of cryopreserved PBMC derived from bone marrow is thawed and PBMCs are counted. PBMCs are co-cultured on a 24-well GRex plate at 5x10 cells per well with anti~CD3 / anti-CD28 antibodies (DynaBeads®) at a 1:1 ratio in approximately 8ml per well of CM-2 cell culture medium (included of R'PMI-1640, human AB serum, 1-glutamine, 2-mercaptaethanol, gentamicin sulfate, AIM-V medium) in the presence of IL-2 at 300.0IU / ml. On day 4, the cell culture medium is exchanged with AIM-V supplemented with additional IL-2 at 30.0.0 IU / ml. On day 7, the expanded MILs are counted. IxlO6 cells per well are transferred to a new 24-well GRex plate and cultured with anti-CD3 / anti-CD28 antibodies (DynaBeads®) at a 1:1 ratio. in approximately 8ml per well of AIM-V medium in the presence of IL-2 at 3G00IU / ml. In the. day 11, cell culture medium is exchanged from AIM-V to CM-4 (comprised of AIM-V medium, 2mM Gluamax, and 3000IU / ml IL2). On day 1.4, the DynaBeads® are. removed using a DynaMag Magnet (DynaMag™!5) and the MILs are counted, MIL Method 2. In one. embodiment of the invention, the method is carried out for 7 days. In one embodiment, the method comprises obtaining bone marrow-derived PBMCs and cryopreserving the PBMCs. On day 0, the PBMCs are cultured with. anti-CD3 / anti-CD28 antibodies (DynaBeads®') in a 3:1 ratio (beads: cells) and IL-2 at 3000 iu / ml. MILs are collected on day 7, the beads are removed, and the MILs are optionally counted and phenotyped. In one embodiment of the invention, MIL Method 2 is performed as follows; In. On day Q, a cryopreserved PBMC sample is thawed and the PBMCs are counted. PBMCs are co-cultured on a GRex plate. 24 wells at 5x105 cells: per well with anti-CD3 / anti-CD2 8 antibodies (DynaBeads") at a 1:1 ratio in approx. 8ml per well of CM-2 cell culture medium (comprised of RPMI -1640, human AB serum, 1-glutamine, 2-me.rcaptoeth.anol, gentamicin sulfate, AIM-V medium) in the presence of IL-2 at 3'OOOIU / ml On day 7, the DynaBeads® are removed using a DynaMag Magnet (pynaMág?*15) and the MILs are counted MIL Method 3. In one embodiment of the invention, the method comprises obtaining PBMCs from bone marrow On day 0, the PBMCs are selected for 'CD3 + / CD33+ / CD20-+ / CD14+ and sorted, and read non-CD3 + / CD33 + . / CD2a+ / CD14+ cell fraction is sonicated and a portion of the sonicated cell fraction is added again to the selected cell fraction IL-2 is added to the cell culture at 3000 lü / ml On day 3, PBMCs are cultured with anti-CD3 / anti-CD28 antibodies (DynaBeads®) in a 1:1 ratio (beads:cells). ) and IL-2 to 3 000 IU / ml. On day 4, additional IL-2 is added to the culture at 3000 IU / ml. On day 7, the culture is again stimulated with anti-CD3 / anti-CD28 antibodies (DynaBeads®) in a 1:1 ratio (beads : cells), and additional IL-2, at 3000 IU / ml, is added to the culture. On day 11, IL-2 is added to the culture at 3000 IU / ml. MI.Ls are harvested on day 14, the beads are removed, and the MILs are optionally counted and phenotyped. In one embodiment of the invention, MIL Method 3 is performed as follows: On day 0, a cryopreserved sample of PBMCs is thawed and the PBMCs are counted. Cells are stained with CD3, CD33, CD20, and CD14 antibodies and sorted using an S3e cell sorter (Bio-Rad). The cells are classified into two fr-actions - an immune cell fraction (or the MIL fraction) (CD3+CD33+CD20eCD144·) and a blaS-to AML cell fraction (non-CD3+CD33+CD.2- 0+CD14+). A number of cells from the AML blast cell fraction that is approximately equal to the number of cells from the immune cell fraction (or MIL fraction) that will be plated on a 24-well GRex plate is suspended in 100U1 medium and sonicated. In this example, about 2.8x104 to about 3.38x105 cells from the blast cell fraction. AML samples are taken and suspended in ICOul of CM2 medium and then sonicated for 30 seconds. The 100 μl of sonicated AML blast cell fraction is added to the immune cell fraction in a 24-well GRex plate. Immune cells are present in an amount of about 2.8x1O4 to about 3.3 8x105 cells per well in about 8ml per well of CM-2 cell culture medium in the presence of IL-2 at -SOOOIU / ml and are cultured with the portion of AML blast cell fraction for approximately 3 days. On day 3, anti-CDS / anti-CD2 8 antibodies (DynaBeads®') at a 1:1 ratio are added to each well and cultured for approximately 1 day. On day 4, the cell culture medium is exchanged with AIM-V supplemented with additional IL-2 at 3000IU / ml. On day 7, the expanded MILs are counted. Approximately 1.SxlO5 up to 4x10"' cells per well are transferred to a new 24-well GRex plate and cultured with anti-CDB / ant1-CD28 antibodies (DynaBeads®) at a 1:1 ratio in approximately 8ml per well of AIM medium. -V in the presence of IL-2 at 3000IU / ml On day 11, the cell culture medium is switched from AIM-V to CM-4 (supplemented with IL-2 at 3000IU / ml) On day 14 , the DynaBeads® are removed using a DynaMag Magnet (DynaMag^lS) and the MILs are optionally counted. In one embodiment of the invention, the PBMCs are obtained from bone marrow. In one embodiment, PBMCs are obtained from bone marrow through apheresis, aspiration, needle biopsy, or other similar means known in the art. In one embodiment, the PBMCs are fresh. In another embodiment, PBMCs are. cryopreserved. In one embodiment of the invention, the method is performed for about 7 days, about 8 days, about 9 days, about 10 days, about 11 days, about 12 days, about 1.3 days, or about 14 days. In another embodiment, the method is performed for about 7 days. In another embodiment, the method is carried out for approximately 14 days, In one embodiment of the invention, PBMCs are cultured with anti-UD3 / anti-CD28 antibodies. In one embodiment, any available .antiCD3. / antiCD28 product is useful in the present invention. In one embodiment of the invention, the commercially available products are 'DynaBeads'. In one embodiment, the DynaBeads® are cultured with the PBMCs on. a ratio of 1:1 (beads:cells). In another embodiment, the antibodies are DynaBeads® cultured with the PBMCs in a ratio of 1.5:1, 2:1, 2..5:1, 3:1, 3.5:1, 4:1, 4.5:1, or 5 :1 (knobs: cells) . In either of the above embodiments, magnetic bead-based selection of an immune cell fraction (or MIL fraction) {CD3+CD33eCD20+CD14+} or an AML blast cell fraction (not CJD3+CD33+CD2) is used. 0+CD14 + ) . In one embodiment of the invention, the steps of culturing the antibody and / or the step of restimulating cells with antibody is performed for a period of from about 2 to about 6 days, from about 3 to about 5 days, or for about 4 days. . In one embodiment of the invention, the step of culturing the antibody is performed for a period of about 2 days, 3 days, 4 days, 5 days, or 6 days. In one embodiment of the invention, the ratio of the. cell number from AML blast cell fraction to cell number from immune cell fraction (or MIL fraction) is about 0.1; 1 to about 10:1. In another embodiment, the ratio is about 0.1:1 to about 5:1, about 0.1:1 to about 2:1, or about 1:1. In one embodiment of the invention, the AML blast cell fraction is optionally altered to disrupt cell aggregation. In one embodiment, the AML blast cell fraction is disrupted using sonication, homogenization, cell lysis, vortexing, or vibration. In another embodiment, the AML blast cell fraction is disrupted using sonication. In one embodiment of the invention, the non-CD3+, non-CD33+, non-CD20+, non-CD14+ cell fraction (AML blast fraction) is lysed using a suitable lysis method, including high temperature lysis, chemical lysis (such as organic alcohols.), enzymatic lysis, and other cell lysis methods known: in the art. In one embodiment of the invention, cells of the AML blast cell fraction are suspended at a concentration of from about 0...2X105 to about 2x10 cells per 100uL and added to cell culture with the immune cell fraction. In another embodiment, the concentration is from about 0.5x105 to about 2x10:s cells per 100uL, from about 0.7x105 to about 2x105 cells per 100uL, from about 1x10s to about 2x105 cells per 100uL, or from about 1.5x105 up to about .2x10- cells per lOOuL. In one embodiment, the PBMC sample is cultured with IL-2. In one embodiment of the invention, the cell culture medium used for expansion of the MILs comprises IL-2 at a concentration selected from the group consisting of about 100 IU / mL, about 200 IU / mb, about 300 IU / mL , about 400 XU / mL, about 100 XU / mL, about 100 XU / mL, about 100 lU / mL, about 100 I.U / mL, about 100 XU / mL, about 500 XU / mL, about 600 Γϋ / mL, approximately 700 XU / mL, approximately 800 XU / mL, approximately 900 XU / mL, approximately 1,000 XU / mL, approximately 1,100 XU / mL, approximately 1,200 IU / mL, approximately 1,300 IU / mL, approximately- 1,400 IU / mL, approximately 1,500 IU / mL, approximately 1,600 IU / mL, approximately 1,700 IU / mL, approximately 1,80.0 IU / mL, approximately 1,900 TU / mL, approximately 2,000 IU / mL, approximately 2,100 lu / mL, approx. 2,200 IU / mL, approximately 2,300 IU / mL, approximately 2,400 IU / mL, approximately 2,500 lu / mL, approximately 2,600 IU / mL, approximately .2,700 IU / mL, approximately 2,800 IU / mL, approximately 2,900 IIJ / mL, approximately 3,000 IU / mL, approximately 3,100 IU / mL, approximately 3,200 IU / mL, approximately 3,300 IU / mL, approximately 3,400 IU / mL, approximately 3,500 IU / mL, approximately 3,600 IU / mL, approximately 3,700 IU / mL, approximately 3,800 TU / mL, .approximately 3,900 IU / mL, approximately 4,000 IU / mL, approximately- 4,100 IU / mL, approximately 4,200 IU / mL, .approximately 4,300 IU / mL approximately 4,400 IU / mL, approximately 4,500 IU / mL, approximately 4,600 IU / mL, approximately 4,700 IU / mL, approximately 4,800 IU / mL, approximately 4,900 IU / mL, approximately 5,000 IU / mL, about 5,100 IU / ml, about 5,200 IU / ml, about 5,.300 IU / ml, about 5,40.0 IU / ml, about 5,500 IU / ml, about nte 5,600 IU / mL, approximately 5,700 IU / mL, approximately 5,800 IU / mL, approximately 5,900 IU / mL, approximately 6.00-0 IU / mL, approximately 6,500 IU / mL, approximately 7.00-0 IU / mL, approximately -7,500 IU / mL, approximately -8,000 IU / mL, approximately 8,500 IU / mL, approximately 9,000 IU / mL, approximately 9,500 IU / mL, and approximately 10.0-00 IU / mL. In one embodiment of the invention, additional IL-2 can be added to the culture in one or more days through the Method. In one embodiment of the invention, additional IL-2 is added on day 4. In one embodiment of the invention, additional IL-2 is added on day 7. In one embodiment of the invention, additional IL-2 is added on on day 11. In another embodiment, additional IL-2 is added on day 4, day 7, and / or day II. In one embodiment of the invention, the MILs are cultured with additional IL-2 for a period of 1 day, 2 days, 3 days, 4 days, 5 days, S days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, or 14 days. In one embodiment of the invention, the MILs are cultured for a period of 3 days after each addition of IL-2. In one embodiment, the cell culture medium is exchanged at least once during the method. In one embodiment, the cell culture medium is exchanged at the same time additional IL-2 is added. In another embodiment, the cell culture medium is exchanged with at least one of day .1, day 2, day 3, day 4, day 5, day δ, day 7, day 8, day 9-, day .10, day 11 , day 12, day 13, or day 14. In one embodiment of the invention, the cell culture medium used throughout the method may be the same or different. In one embodiment of the invention, the cell culture medium is CM-2, CM-4, or AIM-V. In one embodiment of the invention, the cell culture medium exchange step on day 11 is optional. In one embodiment of the invention, the number of starting cells of PBMCs for the expansion process is from about 25,000 to about 1,000,000, from about 30,000 to about 900,000, from about 35,000 to about 850,000, from about 40,000 to about 800,000, from from about 45,000 to about 800,000, from about 50,000 to about 750,000, from about 55,000 to about 700,000, from about 60,000 to about 650,000, from about 6,5,000 to about 600,000, from about 70,00.0 to about 550,000, preferably from about 75,000 to about 500,000, from about 80,000 to about 450,000, from about 85,000 to about 400,000, from about 90,000 to about 350,000, from about 95,000 has t to about 300,000, from about 100,000 to about 250,000, from about 105,000 to about 200,000, or from about 110,000 to about 150,000. In one embodiment of the invention, the starting cell number of PBMCs is about 138,000, 140,000, 145,000, or more. In another embodiment, the starting cell number of PBMCs is approximately 28,000. In another embodiment, the starting cell number of PBMCs is approximately 62,000. In another embodiment, the starting cell number of PBMCs is approximately 338,000. In another embodiment, the starting cell number of PBMCs is approximately 336,000. In one embodiment of the invention, the fold expansion of MILs is from about 20% to about 100%, 25% to about 95%, 30% to about 90%, 35% to about 85%, 40% to about 80%, 45% to about 75%, 50% to about 100%, or 25% to about 75%. In one embodiment of the invention, the expansion times is about 25%. In another embodiment of the invention, the expansion times is about 50%. In another embodiment, the expansion times is about 75%. In one embodiment of the invention, MILs are expanded from 10-0.50 ml of bone marrow aspirate. In one embodiment of the invention, 10 ml of bone marrow aspirate are obtained from the patient. In another embodiment, 20ml of aspirated bone marrow is obtained from the patient. In another embodiment, 30ml of aspirated bone marrow is obtained from the patient. In another embodiment, 40ml of aspirated bone marrow is obtained from the patient. In another embodiment, 50 ml of aspirated bone marrow is obtained from the patient. In one embodiment of the invention, the number of PBMCs provided from about 10-5-Oml of bone marrow aspirate is about 5x107 to about IQxlO7 PBMCs. In another embodiment, the number of PMBCs provided is about 7xl07 PBMCs. In one embodiment of the invention, about 5x107 to about 10x107 of PBMCs provides about 0.5x1.0® to about 1.5x10® expansion of starting cell material. In one embodiment of the invention, approximately 1x10® expansion of starting cell material is provided. In one embodiment of the invention, the total number of MILs collected at the end of the expansion period is from about 0.01x10* to about IxlO9, from about 0.OSxlO3 to about 0.9x10®, from about 0.1x10* to about 0 ..-85x10*, from about .0.15x10"®- to about 0.7x10®, from about 0.2x10* to about 0.65x10*, from about. 0 ..25X10®' to about 0.6x10*, from about -0.3 x10* to about 0.55x10®> from about 0..35x10* to about 0.5x10*, or from about 0.4X10® to about 0.45x1O9. In one embodiment of the invention, 12x10* PBMC derived from bone marrow aspirate provides approximately 1.4xlGs of starting cell material, which provides approximately 1..1x107 MILs at the end of the expansion process. In one embodiment of the invention, MILs expanded from bone marrow PBMCs using MIL Method 3 described above comprise a higher proportion of CD84- cells and lower numbers of LAG3 + and PD1 + cells compared to MILs expanded using MIL Method 1. or MIL Method 2. In one embodiment of the invention, PBLs expanded from PBMC Blood using MIL Method 3 described above comprise a higher proportion of CD8+ cells and increased levels of ΙΡΝγ production compared to PBLs expanded using MIL Method 1 or MIL Method 2. In one embodiment of the invention, the clinical dose of MILs useful for patients with acute myeloid leukemia (AML) ranges from about 4x108 to about 2.5x109 MI Le. In another embodiment, the number of MI.Ls provided in the pharmaceutical compositions of the invention is 9.5 x 108 MILs. In another embodiment, the number of MILs provided in the pharmaceutical compositions of the invention is 4. .IxlO8. In another embodiment, the number of MILs provided in the pharmaceutical compositions of the invention is 2.2x10®, In any of the above modalities, the PBMCs can be derived from a whole blood sample, from bone marrow, by apheresis, from buffy coat, or from another method known in the art for obtaining PBMCs. Methods for expanding TILs Using the "Process *k ¡t -Í-y In one embodiment of the present invention, the invention provides devices and methods for expanding T cells derived from bone marrow and / or peripheral blood. In one embodiment of the invention, the T cells have a higher tumor specificity of the bone marrow microenvironment in a polyclonal antibody but of a highly tumor specific mater. In one embodiment, the bone marrow microenvironment is used to support and expand T cells. In one embodiment of the invention, there is approximately a 25- to 100-fold expansion of TILs in a 7-day or 14-day expansion process. . In one embodiment, the expansion times of TILs is from about 30-92-fold. In one embodiment, the expansion times is from about 35-85-fold. In one embodiment, the expansion times is from about 40-80-fold. In one embodiment, the expansion times is from about 45-75-fold. In another embodiment, the fold expansion is from about 40-7.0-fold. In another embodiment, the expansion times is from about 45-65-fold. In another embodiment, the expansion times is about 25-fold, about 30-fold, about 3-5-fold, about 40-fold, about 45-fold, and 50-fold, about 55-fold, about 60-fold, about 65-fold, about 70-fold, about 75-fold, about 80-fold, about 8 5-fold, about 90-fold, about 95-fold, or about 100-fold expansion. In one embodiment of the invention, the T cell manufacturing process does not require any intervention to select for tumor specificity. In one embodiment of the invention, the T cell manufacturing process does not require the presence of tumor in the marrow and / or peripheral blood at the time of T cell expansion. In one embodiment, the cells. T are expanded in the presence of nearly complete bone marrow. In one embodiment, the invention provides a method for extracting T-cells from bone marrow and / or peripheral blood as described in the Examples, and in particular, Example 21, set forth in WO2010 / 062742, which incorporates herein by reference. In one embodiment, the invention provides a method of extracting T-cells from bone marrow and / or peripheral blood as described in, for example, Noonan, et al., 2005, Cancer Res. 65:2026-2034, the which is incorporated herein by reference. In. a modality. Methods for obtaining bone marrow and / or peripheral blood that are known to those of skill in the art are useful in the present invention. In one embodiment of the invention, bone marrow and / or peripheral blood are obtained using needle aspiration. In one embodiment of the invention, bone marrow from a patient is aspirated into syringes, containing heparin, and stored overnight at room temperature. In one embodiment of the invention, after storage, the contents of the syringes are combined together in a sterile container and tested for quality. Bone marrow is enriched for mononuclear cells (MNCs) using lymphocyte separation medium (LSM) and centrifugation with a COBE Spectra. The cells on the gradient are harvested to red blood cells and washed using HBSS. The MNCs are cryopreserved using a heta-starch cryoprotectant supplemented with 2% HSA and 5% DMSO, reserving some of the MNCs for quality control. The QC vial is thawed to determine the CD34' and CD38* / 138* cell count of the MNC product. It is important to note that bone marrow harvest is not a limitation to the present invention. In one embodiment of the invention, bone marrow is aspirated and fractionated in a density gradient lymphocytic separation medium and cells are harvested near the level of the red cell pellet. In one embodiment, this fractionation method substantially removes red blood cells and neutrophils, providing nearly complete bone marrow. In one embodiment, the resulting fractionated material is T-cells and tumor cells. In one embodiment of the invention, the methods can be practiced without a T cell-specific separation step, and without a tumor cell separation step, such as, for example, without labeling T cells with antibodies or other detectable labels. cell-type specific, and without sorting using fluorescence-activated cell sorting (FACSJ. In one embodiment of the invention, the bone marrow obtained is Ficolled or peripheral blood is suspended under serum-free conditions at 1 x 10 ® cells / ml in AFM-V medium at .2 0 OuL· / well. In one embodiment of the invention, bone marrow is harvested from a subject who is not in complete remission. In one embodiment of the invention, bone marrow is harvested from a subject who is in complete remission. In one embodiment of the invention, bone marrow may be obtained and frozen. In one embodiment, bone marrow can be obtained and immediately used to extract T cells. In further embodiments and in accordance with any of the foregoing, the invention provides a method of expanding TILs, the method comprising contacting a population of TILs comprising at least one TIL derived from a liquid tumor. All discussion of expanding TILs herein is applicable to the expansion of TILs obtained from bone marrow, peripheral blood, and / or a. hematological neoplasm, which includes a liquid tumor. In one embodiment, the invention provides a process for the preparation of. a population of tumor infiltrating lymphocytes (TILs) from a tumor, the process comprises the steps of: (a) contacting a fragmented tumor with a first cell culture medium; (b) performing an initial expansion (pre -REP) of the first population of TILs in the first cell culture medium to obtain a second population of TILs, wherein the second population of TILs is at least 5-fold greater in number than the first population of TILs, wherein the first cell culture medium comprises IL-2,-(c) performing a second expansion of the second population of TILs in a second cell culture medium to obtain a third population of TILs, where the third population of TILs is al less than 50-fold greater in number than the second population of TILs after 7 days from the start of the second expansion; wherein the second cell culture medium comprises IL-2, OKT-3 (anti-CD3 antibody), irradiated allogeneic peripheral blood mononuclear cells (PBMCs); and wherein the second expansion is performed over a period of 14 days or less, · (d) collecting the third population of TILs; and wherein the tumor is a liquid tumor, and wherein the cancer is a hematologic malignancy. In one embodiment, the invention provides a process for expanding a population of TILs that includes a first fast pre-expansion process (pre-REP) and then a second process (which may be a fast expansion ~REP process), wherein the cell culture medium used for expansion comprises IL-2 at a concentration selected from the group consisting of between 100 TU / mL and 10,000 IU / mL, between 200 IU / mL and 5,000 IU / mL,. between 300 Iü / mL and 4,800 TU / mL, between 400 IU / mL and 4,600 TU / mL, between 500 Iü / mL and 4,400 Iü / mL, between 600 Iü / mL and 4,200 TU / mL, between 700 XU / mL and 4.0-00 Iü / mL, between 800 Iü / mL and 3,800 Iü / mL, between 900 Iü / mL and 3,600 Iü / mL, between 1,000 Iü / mL and 3,400 Iü / mL, between 1,100 Iü / mL and 3,200 Iü / mL, between 1,200 IU / mL and 3,000 XU / mL, between 1,300 IU / raL and 2,800 IU / mL, between 1,400 IU / ml and 2,600 IU / ml, between 1,500 IU / ml and 2.40 0: IU / ml, between 1.6 00 IU / ml and 2.2 00 TU / mL, between 1,700 IU / ml and 2,000 IU / ml, between 5,500 IU / mL and 9,500 IU / ml, between 6,000 IU / mL and 9,000 IU / mL, between 6.500 IU / mL and 8,500 IU / mL, between 7,000 IU / mL and §,000 IU / mL, and between 7,500 IU / mL and 8,000 IU / mL. In one embodiment, the invention provides a process for expanding a population of TILs that includes a rapid pre-expansion process (.pre-REP) and a . rapid expansion process (REP), wherein the cell culture medium used for expansion comprises IL-2a. a selected concentration. from the group consisting of about 100 IU / mL, about 200 IU / mL, about 300 IU / mL, about 400 IU / mL, about LOO IU / mL, about 100 IU / mL, about 100 IU / mL, about 100 IU / mL, approximately 100 IU / mL, approximately 500 IU / mL, approximately 600 IU / mL, approximately 700 IU / mL, approximately 800 IU / mL, approximately 900 IU / mL, approximately 1,000 IU / mL, approximately 1,100 IU / mL, approximately 1,200 IU / mL, approximately 1,300 IU / mL, approximately 1,400 IU / mL, approximately 1,500 IU / mL, approximately 1,600 IU / mL, approximately 1,700 IU / mL, approximately 1,800 IU / mL mL, approximately 1,900 IU / mL, approximately 2,000 IU / mL, approximately 2,100 IU / mL, approximately 2,200 IU / mL, approximately 2,300 IU / mL, approximately 2,400 IU / mL, approximately 2,500 IU / mL, approximately 2,600 IU / mL, approximately 2,700 IU / mL, approximately 2,800 IU / mL, approximately 2,900 IU / mL, to approximately 3,000 IU / mL, approximately 3,100 IU / mL, approximately 3,200 IU / mL, approximately 3,300 IU / mL, approximately 3,400 IU / mL, approximately 3,500 IU / mL, approximately 3,600 IU / mL, approximately 3,700 IU / mL, approximately 3,800 IU / mL, approximately 3,900 IU / mL, approximately 4,000 IU / mL, approximately 4,100 IU / mL, approximately 4,200 IU / mL, approximately 4,300 IU / mL, approximately 4,400 IU / mL, approximately 4,500 IU / mL, approximately 4,600 IU / mL mL, approximately 4,700 IU / mL, approximately 4,800 IU / mL, approximately 4,900 IU / mL, approximately 5,000 IU / mL, approximately 5,100 IU / mL, approximately 5,200 IU / mL, approximately 5,300 IU / mL, approximately 5,400 IU / mL, approximately 5,500 IU / mL, approximately 5,600 IU / mL, approximately 5,700 IU / mL, approximately 5,800 IU / mL, approximately 5,900 IU / mL, approximately 6,000 IU / mL, approximately 6,500 IU / mL, approximately 7,000-IU / mL, about 7,500 IU / mL, approx. te 8,000 IU / mL, approximately 8,500 IU / mL, approximately 9,000 IU / mL, approximately 9,500 IU / mL, and approximately 10,000 IU / mL. In one embodiment, the invention provides a process for expanding a population of TILs that includes a rapid pre-expansion (pre-REP) process. In one embodiment, the invention provides a pre-RSP process for expanding a population of TILs, the pre-REP process comprising the steps of contacting the population of TILs obtained from a liquid tumor with a cell culture medium, wherein the cell culture medium further comprises IL-2 at an initial concentration of between 1000 IU / mL· and 6000 Iü / mL. In one embodiment, the invention provides a pre-REP process for expanding a population of TILs, the process comprising the steps of contacting the population of TILs obtained from a liquid tumor with a cell culture medium, wherein the cell culture medium further comprises IL-2 at an initial concentration of approximately: 6000 Iu / mL. In one embodiment: REP can be performed in a permeable container. gas using the TILs obtained from a liquid turn in accordance with the present description by any suitable method. For example, TILs can be rapidly expanded using non-specific T cell receptor stimulation on the. presence of inter.r'leukin-2 (IL-2) or interl encin--15 (IL-15). Non-specific T cell receptor stimuli can include, for example, approximately 30 ng / mL of OKT-3, an anti~CD3 monoclonal antibody (commercially available from Ortho-McNeil, Raritan, NJ or Miltenyi Biotech, Achuru, CA). TILs can be rapidly expanded by further stimulating the TILs in vitro with one or more antigens, including antigenic portions thereof, such as epitopes), from cancer, which may optionally be expressed from such a vector. as a human leukocyte antigen A2 (HLA-A2) binding peptide, eg, 0.3 µM MART-1:26-35 (27 L) or gpl 00:209-217 (210.M), optionally in the presence of a T-cell growth factor, such as 30G IU / mL of IL-2 or IL-15. Other suitable antigens may include, eg, NY-ESQ-1, TRP-1, TRP-2, tyrokinase cancer antigen, MAGE-A3, SSX-2, and VEG.FR2, or antigenic portions thereof. The TIL can also be rapidly expanded by restimulating the same pulsed cancer antigen(s) in HLA-A2 expressing antigen presenting cells. Alternatively, the TILs can be further restimulated with. for example, autologous, irradiated lymphocytes, or with irradiated allogeneic HLA-A2+ lymphocytes and IL-2. In one embodiment, a method of expanding TILs may include using about 5,000 mL to about 250-00 mL of cell culture medium, about 5,000 mL to about 10,000 mL of cell culture medium, or about 5,800 mL to about 8,700 mL of. cell culture medium. In one embodiment, a method of expanding TILs may include using about 1,000 mL to about 2,000 mL of cell media, about 2,000 mL to about 3,000 mL of cell culture media, about 3,000 mL to about 4,000 mL of cell culture media. , about 4,000 mL to about 5,000 mL of cell culture medium, about 5,000 mL to about 6,000 mL of cell culture medium, about 6,000 mL to about 7,000 mL of cell culture medium, about 7,000 mL to about 8,000 mL of medium cell culture medium, approximately 8,000 mL to approximately 9,000 mL cell culture medium, approximately 3,000 mL to approximately 10,000 mL cell culture medium, approximately 1000 mL to approximately 15,000 mL cell culture medium, approximately 15,000 mL to approximately 20,000 mL of cell culture medium, or approximately 2000 0 mL to approximately 25,000 mL of cell culture medium. In one embodiment, expanding the number of TILs uses no more than one type of cell culture medium. Any suitable cell culture medium can be used, for example, AIM-V cell culture medium (L-glutamine, 50 uM streptomycin sulfate, and 10 uM gentamicin sulfate) (Invitrogen, C&rlsbad CA). In this sense, the inventive methods advantageously reduce the amount of medium and the number of types of medium required to expand the number of TIL·. In one embodiment, expanding the number of TILs may comprise feeding the cells no more frequently - than every third or fourth day. Expanding the number of cells in a gas-permeable container simplifies the procedures needed to expand the number of cells by reducing the frequency of feeding needed to expand the cells. In one embodiment, a second expansion is performed using a gas permeable container. Such modalities allow cell populations to expand from approximately 5 x Ί05 cells / cm2 to between ID x 1:06 and 30 x 10* cells / cm2. In one embodiment, this expansion occurs without power. In one embodiment, this expansion occurs without feeding to the extent that the medium resides at a height of about 10 cm in a gas-permeable flask. In one embodiment this is without feeding but with the addition of one or more cytokines. In one embodiment, the cytokine. it can be added as a bolus without any need to mix the cytokine with the medium. Such containers, devices, and methods are known in the. and have been used to expand TILs, and include those described in US Patent Application Publication No. US 2014 / 0377739 Al, International Patent Application Publication No. WO 2014 / 210036 Al, US Patent Application Publication No. US 2,013 / 0115617 Al, International Publication No. WO 2013 / 18-8427 Al, US Patent Application Publication No. US 2011 / 0136228. Al, US Patent No. 8,809,050, International Patent Application Publication No. WO 2011 / 072088 A2, Patent Application Publication. US Patent Application Publication No. US 2016 / 0208216 Al, US Patent Application Publication No. US 2012 / 0244133 Al, International Patent Application Publication No. WO 2012 / 129201 Al, US Patent Application Publication No. US 2013 / 0102075 Al , US Patent No. 8,956,860, International Patent Application Publication No. WO 2013 / 173835 Al, and US Patent Application Publication No. ÜS 2015 / 0175966 Al, the disclosures of which are incorporated herein by reference. Such processes are also described in Ji-n, et al,. J.Immunatherapy 2012,. 35, 283-292, the disclosure of which is incorporated by reference herein. In one embodiment, the gas permeable container is a G-Rex 10 flask (Wilson Wolf Manufacturing Corporation, New Brighton, MN, USA). · In one embodiment, the gas-permeable container includes a gas-permeable culture surface of 10 cm2. In one embodiment, the gas-permeable container includes a capacity of. 40 mL cell culture medium. In one embodiment, the gas-permeable container provides 100 to 300 million TILs after 2 medium exchanges. In one embodiment, the gas permeable container is a G-Rex 100 flask (Wilson Wolf Manufacturing Corporation, New Brighton, MN, USA). In one embodiment, the gas-permeable container includes a gas-permeable culture surface of 100 c.m2. In one embodiment, the gas permeable container includes a cell culture medium capacity of 4-50 mL. In one embodiment, the gas permeable container provides 1 to 3 billion TILs after 2 media exchanges. In one embodiment, the gas permeable container is a G-Rex 1GQM flask (Wilson Wolf Manufacturing Corporation, New Brighton, MN, USA). In one embodiment, the gas-permeable container includes a gas-permeable culture surface of 100 cm2. In one embodiment, the gas permeable container includes a cell culture medium capacity of 1000 mL. In one embodiment, the gas permeable container provides 1 to 3 billion TILs without medium exchange. In one embodiment, the gas permeable container is a G-Rex 100L flask (Wilson Wolf Manufacturing Corporation, New Brighton, MN, USA). In one embodiment, the gas-permeable container includes a gas-permeable culture surface of 108 cm2. In one embodiment, the gas permeable container includes a cell culture medium capacity of 2,000 mL. In one embodiment, the gas permeable container provides 1 up to. 3 billion TILs without medium exchange. In one embodiment, the gas-permeable container is a 24-well G-Rex plate (Wilson Wolf Manufacturing Corporation, New Brighton, MN, USA). In one embodiment, the gas-permeable container includes a plate with cavities, each cavity including a gas-permeable culture surface of 2 cm 2 . In one embodiment, the gas permeable container includes a plate with wells, where each well includes a cell culture medium capacity of 8 mL. In one embodiment, the gas permeable container provides 20 to 60 million cells per well after 2 medium exchanges. In one embodiment, the gas permeable container is a 6-cavity G-Rex plate (Wilson Wolf Manufacturing Corporation, New Brighton, MN, USA) In one embodiment, the gas permeable container includes a plate with cavities, where each cavity includes a gas-permeable culture surface of 10 cm2. In one embodiment, the gas permeable container includes a plate with wells, where each well includes a cell culture medium capacity of 40 mL. In one mode, the Gas-permeable container provides 100 to 300 million cells per well after 2 medium exchanges. In one embodiment, the cell medium in the first and / or second gas-permeable containers is unfiltered. The use of unfiltered cell medium can simplify the procedures necessary to expand the number of cells. In a. embodiment, the cell medium in the first and / or second permeable container. gas lacks beta-mercaptoethanol (EME). In one embodiment, the duration of the method comprises obtaining a sample of tumor tissue from the mammal; culturing the tumor tissue sample in a first gas-permeable container containing the cell medium therein; obtain TILs from the tumor tissue sample; expand the. number of TILs in a second gas-permeable container containing the cell medium therein for a duration of from about 14 to about 42 days, eg, about 28 days. In one embodiment, the cell culture medium comprises IL-2. In a preferred embodiment, the cell culture medium comprises about 3000 IU / mL of IL-2. In one embodiment, the cell culture medium comprises about 1,000 IU / mL, about 1,500 IU / mL, about 2,000 IU / mL, about 2,500 IU / mL, about 3,000 IU / mL, about 3,500 IU / mL, about 4,000 IU / mL, mL, approximately 4,500 IU / mL, approximately 5,000 IU / mL, approximately 5,500 IU / mL, approximately 6,000 IU / mL, approximately 6,500 TU / mL, approximately 7,000 IU / mL, approximately 7,500 IU / mL, or approximately 8,000 IU / mL of IL-2. In one embodiment, the cell culture medium comprises between 1000 and 2000 TU / mL, between 2000 and 3000 TU / mL, between 3000 and 4000 Iu / mL, between 4000 and 5000 Iu / mL, between 5000 and 6000 Iu / mL, between 6Q00 and 7000 Iü / mL, between 7000 and 8000 Iü / mL, or between 8000 Iü / mL of IL-2. In one embodiment, the cell culture medium comprises OKT-3 antibody. In a preferred embodiment, the cell culture medium comprises approx. 30 ng / mL of OKT-3 antibody. In one embodiment, the cell culture medium comprises about 0.1 ng / mL, about 0.5 ng / mL, about 1 ng / mL, about 2.5 ng / mL, about 5 ng / mL, about 7.5 ng / mL, about 10 ng / mL, mL, approximately 15 ng / mL, approximately 20 ng / mL, approximately 25 ng / mL, approximately 30 ng / mL, approximately 35 ng / mL, approximately 40 ng / mL, approximately 50 ng / mL, approximately 60 ng / mL , about 70 ng / mL, about 80 ng / mL, about 90 ng / mL, about 100' ng / mL, about 200 ng / mL, about 500 ng / mL, and about 1 pg / mL of OKT-3 antibody . In one embodiment, the cell culture medium comprises between 0.1 ng / mL and 1 ng / mL, between 1 ng / mL and 5 ng / mL, between 5 ng / mL and 10 ng / mL, between 10 ng / mL and 20 ng / mL, between 20 ng / mL and 30 ng / mL, between 30 ng / mL and 40 ng / mL, between 40 ng / mL and 5.0 ng / mL, and between 50 ng / mL and 100 ng / mL of OKT-3 antibody. In one embodiment, the TILs are expanded in gas-permeable containers. Gas-permeable containers have been used to expand TILs using PBMCs, using methods, compositions, and devices known in the art, including those described in US Patent Application Publication No. US Patent Application Publication No. 2005 / 0106'717 Al, the disclosures of which are incorporated herein by reference. In one embodiment, the TILs are expanded in gas-permeable bags. In one embodiment, the TILs are expanded using a cell expansion system that expands TILs in gas-permeable bags, such as the Xuri Cell Expansion System W5 (GE Healthcare). In one embodiment, the TILs are expanded using a cell expansion system that expands TILs in gas-permeable bags, such as the NAVE Bioreactor System, also known as the Xuri Cell Expansion System W5 (GE. Healthcare). In one embodiment, the cell expansion system includes a gas-permeable cell bag with a volume selected from the group consisting of about .109 mL, about 200 mL, about 300 mL, about 400 mL, about 500 mL, about 6 00 mL, approximately 700 mL, approximately 800 mL, approximately 900 mL, approximately 1 L, approximately 2 L, approximately 3 L, approximately 4 L, approximately 5 L, approximately 6 L, approximately 7 L, approximately 8 L, about 9L about 10L about 11L about 12L about 13L about 14L about 15L about 16L about 17L about 18L about 19L about 20L about 25 L, and about 3 0 L. In one embodiment, the cell expansion system includes a gas-permeable cell bag with a -volume range selected from d the group consisting of between 50 and 150 mL, between 150 and 250 mL, between 250 and 350 mL, between 350 and 450 mL, between 450 and 550 mL, between 550 and 650 mL, between 650 and 750 mL, between 750 and 850 mL, between 850 and 950 mL, and between 950 and 1050 mL. In one embodiment, the cell expansion system includes a gas-permeable cell bag with a volume range selected from the group consisting of between 1 L and 2 L, between 2 L and 3 L, between 3 L and 4 L, between 4 L and 5 L, between 5 L and 6 L, between 6 L and 7 L, between 7 L and 8 I>, between 8 L and 9 L, between 9 L and 10 L, between 10 L and 11 L, between 11 L and 12 L, between 12 L and 13 L, between .13 L and 14 L, between 14 L and 15 L, between 15 L and 16 L, between 16 L and 17 L, between 17 L and 18 L, between 18 L and 19 L, and between 19 L and 20 L. In one embodiment, the cell expansion system includes a gas permeable cell bag with a volume range selected from the group consisting of between 0.5 L and 5 L, between 5 L and 10 L, between 10 L and 15 L, between 15 L and 20 L, between 2.0 L and 25 L, and between 25 L and 30 L. In one embodiment, the cell expansion system uses a time of oscillation of about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 1.1 hours, about 12 hours, about 24 hours, about 2 days, about 3 days, about 4 days about 5 days about 6 days about 7 days about 8 days about 9 days about 10 days about 11 days about 12 days about 13 days about 14 days about 15 days about 16 days, about 17 days, about 18 days, about 19 days, about 20 days, about 21 days, about 22 days, about 23 days, about .24 days, about 25 days, about 26 days, about 27 days, and approximately 28 days. In one embodiment, the cell expansion system uses an oscillation time of between .30 minutes and 1 hour, between 1 hour and 12 hours, between 12 hours and 1 day, between 1 day and 7 days, between 7 days and 14 days. , between 14 days and 21 days, and between 21 days and 2:8 days.In one embodiment, the cell expansion system uses an oscillation rate of approximately 2 oscillations / minute, approximately S oscillations / minute, approximately 10 oscillations / minute, approximately 20 oscillations / minute, approximately 30 oscillations / minute, and approximately 40 oscillations. / minute. Without a mode, the cell expansion system uses one. oscillation speed between 2 oscillations / minute and 5 oscillations / minute, S oscillations / minute and 10 oscillations / minute, 10 oscillations / minute and 20 oscillations / minute, 20 oscillations / minute and 30 oscillations / minute, and 30 oscillations / minute and 40 oscillations / minute. In one embodiment, the cell expansion system uses an angle of oscillation of about 2°, about 3°, about 4°, about 5°, about 6°, about 7°, about 86, about 9°, about . 10°, approximately 11°, and approximately 1.2°. In one embodiment, the cell expansion system uses an oscillation angle of between -2® and 3°, between: 3° and 4°, between 4° and 5°, between 5° and 6°, between 6S and 7°, between 7th and 8th, between 8th and 9th, between 9th and 10th, between 10th and 11th, and between 11th and 12th. In one embodiment, a method of expanding TILs obtained from a liquid tumor further comprises a step wherein the TILs are selected for superior tumor reactivity. Any selection method known in the art may be used, for example, the methods described in US Patent Application Publication No. 2Ό16 / 0.010Ό58 Al, the disclosures of which are incorporated herein by reference, may be used. for selection of TILs for superior tumor reactivity, In one embodiment, the invention provides a method of expanding a population of TILs from a fluid tumor, the method comprising the steps as described in Jin, et al., J. Immunotherapy 2012, 35, 283-292, the description of which is incorporated by reference herein. For example, the tumor or portion thereof can be replaced in enzymatic medium and mechanically dissociated for approximately 1 minute. The mixture can then be incubated for 30 minutes at 37°C in 5% C02 and then mechanically disturbed again for approximately 1 minute. After incubation for 30 minutes at 37°C in 5% CCh, the tumor or portion thereof can be mechanically disturbed a third time for approximately 1 minute. If after the third mechanical disruption, large pieces of tissue are present, 1 or 2 additional mechanical dissociations can be applied to the sample, with or without an additional 30 min incubation at 37 eC in 5% CO2 - At the end of the incubation Ultimately, if the cell suspension contains a large number of red blood cells or dead cells, a density gradient separation using Ficoll can be performed to remove these cells. TIL cultures were started on plates. 24-well (Costar 24-well cell culture group, flat bottom; Corning Incorporated, Corning, NY), each well can be seeded with 1 x 10® tumor-digesting cells or a tumor fragment -approximately 1 to 8 mm3 in size in 2 mL of complete medium (CM) with IL-2 (6000 IU / mL; Chiron Corp., Emeryville, CA). CM comprises Roswell Park Memorial Institute Buffer 1640 (RPMIj with GlutaMAX, supplemented with 10% human AB serum, 25 mM Hepes, and 10 mg / mL gentamicin. Cultures can be started in gas-permeable flasks with a 40 mL capacity and a 10 cm2 gas permeable silicon bottom (G-Rex 10; Wilson Wolf Manufacturing, New Brighton, each flask can be loaded with 10-40 x 10® viable tumor digestion cells or 5- 30 tumor fragments in 10-40 mL of CM with TL-2.G-Rex 10 and 24-well plates can be incubated in a humidified incubator at 37 CC in 5% CO2 and 5 days after culture initiation. half of the medium can be removed and replaced, with fresh CM and IL-2 and after day 5, half of the medium can be changed every 2-3 days A second expansion protocol (REP) of TILs can be performed using T-175 flasks and gas permeable bags or G-Rex gas permeable flasks, as described elsewhere in the present, using TILs obtained from the liquid tumors of the present description. For REP in T-175 flasks, 1 x 10* TILs can be suspended in 150 mL of medium in each flask. TILs can be cultured in a 1 to 1 mixture of CM medium and AIM-V (50 / 50 medium), supplemented with 3000 I'U / mL of IL-2 and 30 ng / mL of anti-CD3 antibody ( OKT-3). T-175 flasks can be incubated at 37°C in 5% CQz. Half of. medium can be changed on day 5 using 50 / 50 medium with 3000 IU / mL IL-2. On day 7, cells from 2 T-175 flasks can be combined in a 3-L bag and 300 mL of AIM-V with 5% human AB serum and 3000 IU / mL of IL-2 can be combined. be added to 300 mL of TIL suspension. The number of cells in each bag can be counted every day or two, and fresh medium can be added to keep the cell count between 0.5 and 2. Οχ 106 cells / mL. For REP in 500 mL capacity flasks with 100 cm2 gas permeable silicon bottoms (eg, G-Rex 100, Wilson Wolf Manufacturing, are as described elsewhere herein), 5 x 10d or 10 x 106 TILs can be cultured in 400 mL of 50 / 50 medium, supplemented with 3000 IU / mL of IL-2 and 30 ng / mL of anti-CD3 antibody (OKT-3.). G-RexlOO flasks can be incubated at 3-7°C in 5% CO2. On day five, 250 mL of supernatant can be removed and placed in centrifuge bottles and centrifuged at 1500 rpm (491 g) for 10 minutes. The TIL pellets obtained can be resuspended with 150 mL of 5-0 / 50 fresh medium containing 3000 μl / mL of IL-2 and added back to the G-Rex 100 flasks.When TILs are serially expanded in G-Rex 100 flasks, on day seven, the TILs in each G-RexlOO are suspended in 300 mL of media present in each flask, and the cell suspension can be divided into three 100-mL aliquots. can be used to seed 3 G-RexlOQ flasks. Approximately 150 mL of AIM-V with 5% human AB serum and 3000 IU / mL of IL-2 can then be added to each flask. G-Rex 100 flasks can then be incubated at 37 °C in 5% CO, and after four days, 150 mL of AIM-V with 3000 TU / mL IL-2 can be added to each G-Rex flask. 100. Following this, the REP can be completed by harvesting cells on day 14 of culture. In one embodiment, a method of expanding or treating a cancer includes a step wherein TILs are obtained from a patient's tumor sample. A tumor sample from the patient can be obtained using methods known in the art. For example, TILs can be cultured from enzymatic tumor digests and sharply dissected tumor fragments (about 1 to about 8 mm 3 in size). Such tumor digestions can be produced by incubation in 1640 buffer of enzymatic medium (for example, Roswell Park Memorial Institute (RPMI), 2 mM glutamate, 10 mcg / mL gentamicin, 30 units / mL DNase, and 1.0 mg / mL collagenase) followed by mechanical dissociation (eg, using a tissue dissociator). Tumor digestions can be produced by placing the tumor in enzymatic medium and mechanically dissociating the tumor for approximately 1 minute, followed by incubation for 3 0 minutes at 3 7 ®C in 5% CO.2, followed by repeated cycles of dissociation and dissociation. mechanical incubation under the above conditions until only small pieces of tissue are present. At the end of this process, if the cell suspension contains a large number of red blood cells or dead cells, a density gradient separation using FICOLL hydrophilic branched polysaccharide can be performed to remove these cells. Alternative methods known in the art may be used, such as those described in US Patent Application Publication No. 2012 / 0244133 Al, the disclosure of which is . incorporated by reference herein. Any of the above methods can be used in any of the modalities described herein for methods of expanding TILs or methods of treating a cancer. In one embodiment, the second / REP expansion process for TILs can be performed using T-175 flasks and gas permeable bags as previously described (Tran, et al., J. Immunother. 2008, 31, 742-51; Dudley , et al., J. Imunother. 2003, 26, 332-42 or gas-permeable culture articles (G-Rex flasks, commercially available from Wilson Wolf Manufacturing Corporation, New Brighton, MN, USA). TIL in T-175 flasks, 1 x 10® TILs suspended in 150 raL of medium can be added to each T-175 flask TILs can be grown in a 1:1 mixture of CM medium and AIM-V, supplemented with 3 000 IU (international units) per mL of IL-2 and 30 ng per mL of anti-CD.3 antibody (eg, OKT-3)....T-175 flasks can be incubated at 37°C in 5% of C02 Half of the medium can be exchanged on day Susandci 50 / 50 medium with 3000 IU per mL IL-2 On day 7 cells from two T-175 flasks can be combined into one 3 L bag and 3 80m μL of AIM-V with 5% human AB serum and 3000 IU per mL of IL-2 was added to 300 mL of TIL suspension. The number of cells in each bag is counted every day or two and fresh medium was added to keep the cell count between 0.5 and 2. Q x 106 cells / mL. In one embodiment, for second / expansion of TIL REP in 500 mL capacity gas permeable flasks with 100 cm 2 gas permeable silicon bottoms (G-Rex 100, commercially available from Wilson Wolf Manufacturing Corporation, New Brighton, MN, USA), 5 x 10® or 10 x 10® TILs can be cultured in 400 mL of 50 / 50 medium, supplemented with 5% human .AB serum, 300Q TU per mL of IL-2 and 30 ng per mL of anti-CD3 (OKT-3), G-Rex 100 flasks can be incubated at 37°C in 5% C02. On day 5, 250 mL of supernatant can be removed and placed in centrifuge bottles and centrifuged at 1500 rpm (revolutions per minute; 491 x g) for 10 minutes. TIL pellets can be re-suspended with 150 mL fresh medium containing 5% human AB serum, 3000 IU per mL IL-2, and added back to the original G-Rex 100 flasks. When TILs are serially expanded in G-Rex 100 flasks, on day 7 the TILs in each G-Rex 100 flask can be suspended in the 300 mL of medium present in each flask and the cell suspension divided into 3 aliquots. of 100 inL that can be used to seed 3 G-Rex 100 flasks. Then, 150 mL of AFM-V with 5% human AB serum and 3000 IU per mL of IL-2 can be added to each flask. G-Rex 100 flasks can be incubated at 37°C in 5% CO2 and after 4 days 150 mL of AIM-V with 3000 IU per mL of IL-2 can be added to each G-Rex 100 flask. Cells can be harvested on day 14 of culture. In one embodiment, TILs can be prepared as follows. 2 mm3 of tumor fragments are cultured in complete medium (CM) comprised of AIM-V medium (Invitrogen Life Technologies, Carlsbad, CA) supplemented with 2 mM glutamine (Mediateoh, Inc. Manassas, VA), 100 U / mL penicillin (Invitrogen Life Technologies), 100 ug / mL streptomycin (Invitrogen Life Technologies), 5% heat-inactivated human AB serum (Valley Biomedical, Inc. Winchester, VA), and 600 IU / mL rhIL- 2 (Ohiron, Emeryville, CA). For enzymatic digestion of liquid tumors, tumor specimens are sliced ​​in RPMI-1640, washed and centrifuged at 800 rpm for 5 minutes at 15-22 °C, and resuspended in enzymatic digestion buffer (0.2 mg / raL Collagenase and 3Q units / mi e DNase in RPMI-1640) followed by rotation overnight at room temperature. TILs established from fragments can be grown for 3-4 weeks in CM and expanded fresh or cryopreserved in heat-inactivated HAB serum with 10% dimethyl sulfoxide (DMSO) and stored at -18O°C until study time. . Tumor-associated lymphocytes (TAL) obtained from ascites harvests were plated at 3 x 10 6 cells / well of a 24-well plate in CM. TIL growth was inspected around every third day using a low power inverted microscope. A____Modality___Exemplar____of the____Process____of Manuf actuarac_idn de TIL £el__"^proceso_2A") An exemplary TIL manufacturing / expansion process known as process 2A is eg schematically illustrated in Figure 22. In certain aspects, the present methods produce TILs, which are capable of increasing replication cycles after administration to a subject / patient and as such, it may provide additional therapeutic benefits over: older TILs (ie, TILs which have further undergone further replication prior to administration to a subject / patient). The 'characteristics of younger TILs have been described in the literature, for example Ponia, at al-, Scandinavian J'ournal of Immunology, 75:157--167 (2012); Dudley et al., Clin Cancer Res, 16:6122-6131 (2010); Huang et al., J Immunother, 28(3):258-267 (2005); Be.ss.er et al., Clin Cancer Res, 19(17); OF1-OF9 (2013); Besser et al., J Immunother 32:415-423 (2009); Robbins, et al., J Iminunol 2004; 173:7125-7130; Shen et al., J Inwunother, 30:123-129 (2907), Zhou, et al., J Immunother,. 28:53-62 (2005); and Tran, et al., J Immunother, 31:742-751 (2008), all of which are incorporated herein by reference in their entireties. As discussed herein, the present invention may include a step relating to restimulation of cryopreserved TILs to increase their metabolic activity and thus relative salt prior to transplantation into a patient, and methods for testing such metabolic health. . As generally summarized herein, TILs are generally taken from a patient sample and manipulated to expand their number prior to transplantation into a patient. In some embodiments, the TILs may optionally be genetically engineered as discussed below. In some embodiments, TILs can be cryopreserved. Once thawed, they can also be restimulated to increase their metabolism prior to infusion into a patient. In some embodiments, the first expansion (which includes processes referred to as preREP) is shortened compared to conventional expansion methods to 7-14 days and the second expansion (which includes processes referred to as REP) is shortened to 7 days. -14 days, as discussed in detail below, as well as in the examples and figures. Figure 23 illustrates an exemplary 2Ά Process. As illustrated in Figure 23 and further explained in detail below, in some embodiments, the first expansion (Stage B) is shortened to 11 days and the second expansion (Stage D) is shortened to 11 days. In some embodiments, the combination of the first and second expansions (Stage δ and Stage D) is shortened to 22 days, as discussed in detail herein. As will be appreciated, the process illustrated in Figure 23 and described below is exemplary, and the methods described herein encompass alterations and additions to the described steps, as well as any combinations. An exemplary embodiment of this process is described in PCT Application No. PCT / US20X8 / 012633, which is incorporated herein by reference in its entirety. A._STAGE A; Obtain a _tumor_sample from_the_patient In general, TILs are initially obtained from a patient tumor sample ("primary TILs") and then expanded into a larger population for further manipulation as described herein, optionally cryopreserved, restimulated as outlined herein and optionally evaluated for phenotype and metabolic parameters as an indication of Tr liS health. A tumor sample from the patient can be obtained using methods known in the art, generally by surgical resection, needle biopsy, apheresis, or other means to obtain a sample containing a tumor sample and TIL cells. In general, the tumor sample may be from any solid tumor, including primary tumors, invasive tumors, or metastatic tumors. The tumor sample may also be a liquid tumor, such as a tumor obtained from. from a hematologic malignancy. The solid tumor can be of any type, including, but not limited to, breast, pancreatic, prostate, colorectal, lung, brain, kidney, stomach, and skin (including, but not limited to, squamous cell carcinoma, basal, and melanoma)- In some modalities, useful TILs are obtained from malignant melanoma tumors, as these have been reported to have particularly high levels of TILs. In some modalities, the tumor is larger than about 1.5 cm but less than about 4 cm. In some modalities, the tumor is less than 4 cm. Once obtained, the tumor sample is generally fragmented using sharp dissection into small pieces between 1 to about 8 mm3, with about 2-3 mm3 being particularly useful. TILs are grown from these fragments using enzymatic tumor digestion. Such tumor digestions can be produced by incubation in enzyme media (eg, Roswell Park Memorial Institute (RP.MI) 1640 buffer), 2 mM glutamate, 10 mcg / mL gentamicin, 30 units / mL DNase, and 1.0 mg / mL collagenase) followed by mechanical dissociation (eg, using a tissue dissociator). Tumor digestions can be produced by placing the tumor on. enzymatic medium and mechanically dissociating the tumor for approximately 1 minute, followed by incubation for 30 minutes at 37°C in 5% CO followed by repeated cycles of mechanical dissociation and incubation under the above conditions until only small pieces of tissue are present. . At the end of this process, if the cell suspension contains a large number of red blood cells or dead cells, a density-gradient separation using FICOLL hydrophilic branched polysaccharide can be performed to remove these cells. Alternative methods known in the art may be used, such as those described in US Patent Application Publication No. 2012 / 0244133 Al, the disclosure of which is incorporated by reference herein. Any of the above methods may be used. in any of the embodiments described herein for methods of expanding TILs or methods of treating a cancer. In general, the harvested cell suspension is called a "primary cell population" or a "freshly harvested" cell population. In one embodiment, TILs may be initially cultured from enzymatic tumor digests and tumor fragments obtained from patients. In some embodiments, TILs are obtained from tumor fragments. In some modalities, the tumor fragment is obtained by sharp dissection. In some embodiments, the tumor fragment is between approximately 1 mm3 and 10 mm3. In some modalities:, the tumor fragment is between approximately 1 mm3 and 8 mm3. In some embodiments, the tumor fragment is approximately 1 mm3. In some embodiments, the tumor fragment is approximately 2 mm3. In some embodiments, the tumor fragment is approximately 3 mm3. In some embodiments, the tumor fragment is approximately 4 m3. In some embodiments, the tumor fragment is approximately 5 mm3. In some modes, the tumor fragment is approximately 6 mm3. In some embodiments, the tumor fragment is approximately 7 mm3. In some embodiments, the tumor fragment is approximately 8 mm3. In some embodiments, the tumor fragment is approximately 9 mm3'. In some embodiments, the tumor fragment is approximately 10 mm3. In some embodiments, the tumor fragment is approximately 8-27 mm3. In some modalities, approximately the fragment of the tumor is approximately. 10-25mm3. In some -modalities, the tumor fragment is approximately 15-25 mm3. In some embodiments, the tumor fragment is approximately .8-20 na3. In some embodiments, the tumor fragment is approximately 15-20 mm3. In some embodiments, the tumor fragment is approximately 8-15 mm3. In some embodiments, the fragment of the . tumor is approximately 8-10 mm3. In some embodiments, the number of tumor fragments is about 40 to about 50 tumor fragments. .In some embodiments, the number of tumor fragments is about 40 tumor fragments. In some embodiments, the number of tumor fragments is approximately 50 tumor fragments. In some embodiments, the tumor fragment size is about 8-27 mm3 and there are less than about 50 tumor fragments. In some embodiments, TTLs are obtained from tumor digests. In some embodiments, tumor digests were generated by incubation in enzyme media, eg, but not limited to RPMI 1640, 0.2mM Gluamax,. Gentamicin 10 mg / mL, DNase 30 U / mL, and collagenase 1.0 rag / mL, followed by mechanical cleavage (GentleMACS, Miltenyi Biotec, Auburn, CA). After placing the tumor in enzyme medium, the tumor can be mechanically dissociated for approximately 1 minute. The solution can then be incubated for 30 minutes at 37 °C in 5% -CO2 and then mechanically disturbed again for approximately 1 minute. After being incubated again for 30 minutes at 37 °C in 5% CO, the tumor can be mechanically disturbed a third time for approximately 1 minute. In some embodiments, after the third mechanical disruption, if large pieces of tissue are present, 1 or 2 additional mechanical disruptions are applied to the sample, with or without an additional 30 min incubation at 37°C in S% C02- In In some embodiments, at the end of the final incubation, if the cell suspension contains a large number of red blood cells or dead cells, a density gradient separation using Ficoll can be performed to remove these cells. S.. STAGE. B : First._Sxpansion After dissection or digestion of tumor fragments in stage A, the resulting cells are cultured in serum containing T.L-2 under conditions that favor the growth of TILs on tumor and other cells. In some embodiments, tumor digests are incubated in. 2 mL wells in medium comprising 6000 IU / mL inactivated human AB serum. IL-2. This population of primary cells is cultured, for a period of days, generally from 3 to 14 days, resulting in a population of TIL by volume, generally approximately 1 x 108 TIL cells by volume. In some embodiments, this The primary cell population is cultured for a period of 7 to 14 days, resulting in a TIL volume population, generally approximately 1 x 1.0a TIL volume cells. In. In some embodiments, this population of primary cells is cultured for a period of 10 to 14 days, resulting in a population of TIL volumes, generally approximately 1 x 108 TIL cells volume. In some embodiments, this primary cell population is cultured for a period of about 11 days, resulting in a TIL population by volume, generally about 1 x 10 8 TIL cells by volume. In some embodiments, this population of primary cells is cultured for a period of about 11 days, resulting in a population of TIL volumes, generally less than or equal to up to about 200x10 ® TIL cells volume. In a preferred embodiment, expansion of TILs can be performed using an initial volume TIL expansion stage (Stage B as depicted in Figure .23, which may include processes referred to as pre-REP) as described below and herein, followed by a second expansion (Stage D, which includes processes referred to as rapid expansion protocol (REP) stages) as set forth below under Stage D and herein, followed by optional cryopreservation, and followed by a second Stage D (which includes processes referred to as REP stages of restimulation) as described below and here. The TILs obtained from this process can be optionally characterized by phenotypic characteristics and metabolic parameters - as described herein. In modalities where TIL cultures are started in 24-well plates, for example, using flat-bottomed Costar 2:4-well cell culture pool (Corning Incorporated, Corning, NY, each well can be seeded with 1 x 10 ® tumor-digested cells or a 2mL tumor fragment of complete medium (CM) with IL-2 (600Q IU / mL; Chiron Corp., Emeryville, CA).In some embodiments, the tumor fragment is between about 1 mm3 and 10 mm3. In some embodiments, the CM for Step B consists of RPMI 1640 with GlutaMAX, supplemented with 10% human AS serum, 25mM PEPES, and 10mg / mL gentamicin. In modalities where cultures are started in gas-permeable flasks with a capacity of 40 mL and a gas-permeable silica bottom of 10 cm2 (for example, G-RexlO; Wilson Wolf Manufacturing, New Brighton, MN) (Fig. 1) Each flask was loaded with 10-40 x 10 tumor-digested viable cells or 5"30 tumor fragments in 10-40 mL of IL-2 CM. Both G-RexlO and 24-well plates were incubated in a humidified incubator at 37 °C in 5% CQs and 5 days after the start of culture, half of the medium was removed and replaced with fresh CM and IL-2 and after day 5, half of the medium it was changed every 2-3 days. In one embodiment, the cell culture medium further comprises IL-2. In a preferred embodiment, the cell culture medium comprises about 3000 IU / mL of IL-2. In one embodiment, the cell culture medium comprises about 1000 ΧΠ / mL, about 1500 XU / mL, about 2000 IU / mL, approximately 2,500 XU / mL, approximately 3,000 XU / mL, approximately: 3,500 XU / mL, approximately 4,000 XU / mL, approximately 4,500 XU / mL, approximately 5,000 XU / mL, approximately 5,500 XU / mL, approximately 6,000 Iü / mL, approximately 6500 Iü / mL, approximately 7000 Iü / mL, approximately 7500 Iü / mL, or approximately 8000 XU / mL of IL-2. In one embodiment, the cell culture medium comprises between 1000 and 2000 XU / mL, between 2000 and 3000 XU / mL, between .3000 and 4000 XU / mL, between 4000 and 5000 Iü / mL, between 5000 and 6000 XU / mL , between 6000 and 7000 XU / mL, between 7000 and 8000 IU. / mL, or between 8000 Iü / mL of IL-,2. In some embodiments, the first expansion process (which includes processes referred to as the pre-REP; Stage B) is shortened to 3-14 days, as discussed in the examples and figures. In some embodiments, the first Stage B expansion is shortened to 7-14 days, as discussed in the Examples and shown in Figures 4 and 5. In some embodiments, the first Stage B expansion is shortened. up to 10-14 days, as discussed in the Examples. In some embodiments, the first expansion of Stage B is shortened to 1.1 days, as discussed in the Examples. In some embodiments, IL-2, IL-7, IL-15, and IL-21 as well as combinations thereof may be included during the Step B processes as described herein. In some embodiments, Step B is performed in a closed system bioreactor. In some embodiments, a closed system is employed for TIL -expansion, as described herein. In some embodiments, a single bioreactor is used. In some embodiments, the single bioreactor used is, for example, a GREX-10 or a GREX·-100. C. STAGE C:__Transition from First Expansion to Second Expansion In some embodiments, the volume TIL population of . the. Step B can be cryopreserved immediately, using methods known in the art and described herein. Alternatively, the bulk TIL population can be subjected to a second expansion (REP) and cryopreserved. as discussed below. In some embodiments, the Stage B TILs are not shortened and the Stage B TILs proceed directly to Stage D. In some embodiments, the transition occurs in a closed system, as further described herein. D. STAGE D¿ Second Expansion In some embodiments, the TIL cell population is expanded in number after the harvest and initial bulking process (ie, after Stage A and Stage B). This is referred to herein as the second expansion, which may include expansion processes generally referred to in the art as a rapid expansion process (REP). The second expansion is generally performed using culture medium comprising a number of components, including feeder cells, a cytokine source, and an anti-CD3 antibody, in a gas-permeable container. In some embodiments, the second expansion may include scaling in order to increase the number of TILs obtained in the second expansion. In one embodiment, REP and / or second expansion can be performed in a gas-permeable container using the methods of the present disclosure. For example, TILs can be rapidly expanded using stimulation. de.l nonspecific T-cell receptor in the presence of interleukin-2 (IL-2) or interleukin-15 (IL-15). Nonspecific T-cell receptor stimulation can include, for example, about 30 ng / mL of OKT3, a mouse anti-CD3 monoclonal antibody (commercially available from Ortho-McNeil, Raritan, NJ or Miltenyi Biotech, Auburn, CA). . TILs can be rapidly expanded by further stimulation of TILs in vitro with one or more antigens, including non-antigenic portions thereof, such as cancer epitope(s), which may optionally be expressed from a vector, such as as a human leukocyte antigen Ά2 (HLA-A2) binding peptide, for example, 0.3 μM of MART-1:26-35 (27 L) or gpl 00:209-217 (2ION), optionally in the presence of a T-cell growth factor, such as 30.0 IXJ / mL IL-2 or IL-15, Other suitable antigens may include, for example, NY-ESO-1, TRP-1, TRP-2, antigen tyrckinase carcinogen, MAGE-A3, SSX-2, and VEGFR2, or antigenic portions thereof. TILs can also be rapidly expanded by restimulation with the same pulsed cancer antigen(s) in HLA-A2 expressing antigen presenting cells. Alternatively, TILs can be further restimulated with, for example, irradiated autologous lymphocytes, or irradiated allogeneic HLA-A2+ and IL-2 lymphocytes. In one embodiment, the cell culture medium further comprises IL-2. In a preferred embodiment, the cell culture medium comprises about 3000 IU / mL of IL-2. In one embodiment, the cell culture medium comprises about 1000 IU / mL, about 1500 XU / mL, about 2000 TU / mL, about 2500 IU / mL, about 3000 XU / mL, about 3500 IU / mL, about 4000 XU / mL, approximately 4500 IU / mL·, approximately 5000 IU / mL, approximately. 5500 IU / mL, approximately 6000 IU / mL, approximately 6500 IU / mL, approximately 7000 IU / mL, approximately 7500 IU / mL, or approximately. 8000 TU / 'mL of IL-2. In one embodiment, the cell culture medium comprises - between 1000 and 2000 ip / mL, between 2000 and 3000 Iü / mL, between 3000 and 4000 Iü / mL, between 4000 and 5000 XU / mL, between .5000 and 600.0 Iü / mL, between 60.00 and 7000 Iü / mL, between 7000 and 8000 Iü / mL, or between 80-00 Iü / mL of IL-2. In one mode, the cell culture medium comprises OKT3 antibody. In a preferred embodiment, the cell culture medium comprises approximately 30 ng / mL of QKT'3 antibody. In one embodiment, the cell culture medium comprises about 0.1 ng / mL, about 0.5 ng / mL, about 1 ng / mL, about 2.5 ng / mL, about 5 ng / mL, about 7.5 ng / mL, about 10ng / mL,. approximately 15 ng / mL, approximately 20 ng / mL, approximately 25 ng / mL, approximately 30 ng / mL, approximately 35 ng / mL, approximately 40 ng / mL, approximately .50 ng / mL, approximately 60 .ng / mL, about 70 ng / mL, about 80 ng / mL, about 90 ng / mL, about 100 ng / mL, about 2.00 ng / mL, about 500 ng / mL, and about 1 pg / mL of OK.T3 antibody. In one embodiment, the cell culture medium comprises between 0.1 ng / mL and 1 ng / .mL, between 1 ng / mL and 5 ng / mL, between 5 ng / mL and .10 ng / mL, between 10 ng / mL and 20 ng / mL, between 20 ng / mL and 30 ng / mL, between 30 ng / mL and 40 ng / mL, between 40 ng / mL and 50 ng / mL, and between 50 ng / mL and 100ng / mL. of OKT.3 antibody. In some embodiments, IL-2, IL-7, IL-15, and IL-21 as well as combinations thereof may be included during the second expansion in step D processes as described herein. In some embodiments, the second expansion can be conducted, in a supplemented cell culture medium comprising IL-2, OKT-3, and antigen presenting feeder cells. In some embodiments the antigen presenting feeder cells (APCs) are PBMCs. In one embodiment, the ratio of TILs to PBMCs and / or antigen presenting cells in the rapid expansion and / or the second expansion is about 1 to 25, about 1 to 5-0, about 1 to 100, about 1 to 125, about 1 to 150, about 1 to 175, about 1 to 200, about 1 to 225, about 1 to about 250. 1 to 275, about 1 to 300, about 1 to 325, about 1 to 3.50, about 1 to 375, about 1 to 400, or about 1 to 500. In one embodiment, the ratio of TILs to. PBMCs in rapid expansion and / or second expansion is between 1 to 50 and 1 to 300. In one embodiment, the ratio of TILs to PBMCs in rapid expansion and / or second expansion is between 1 to 100 and 1 to 200. . In one embodiment, REP and / or the second expansion is performed in flasks with the volume TILs being mixed with a 100- or 200-fold excess of inactivated feeder cells, 30 mg / m.L of anti- CD3 OKT3 and 3000 XU / mL of IL-2 in 15 0 ml of media. Medium replacement (generally 2 / 3 medium replacement by breathing with fresh medium) is done until the cells are transferred to an alternate growth chamber. Alternative growth chambers include GRex flasks and gas permeable containers as discussed fully below. In some embodiments, the second expansion (also referred to as the REP process) is shortened to 7-14 days, as discussed in the examples and figures. In some modes, the second expansion is shortened to 11 days. In one embodiment, REP and / or the second expansion can be performed using T-175 flasks and gas permeable bags as previously described (Tran, et al., J. Immunother. 2008, 3.1, 742-51; Dudley, . et al., J. Immunother. 2003, 26, 332-4.2) or gas-permeable culture article (G-Re-x flasks). For rapid expansion and / or second expansion TILs in T-175 flasks, 1 x 10s TILs suspended in 150 mL of medium can be added to each T-175 flask. TILs can be cultured in a 1:1 mixture of CM medium and AIM-V, supplemented with 3000 R7 per mL of IL-2 and 30 ng per mL of anti-CD3. T-175 flasks can be incubated at 37°C in 5% CO2·. Half of the medium can be exchanged on day 5 using 5.0 / 5.0 medium with 3000 IU per mL of IL-2. On day 7 cells from the two T-175 flasks can be combined in a 3 L bag and 300 mL AIMV with 5% human AB serum and 3000 R7 per mL IL-2 added to 300 mL. of TIL suspension. The number of cells in each bag was counted every third day or two and fresh medium was added to maintain the cell content between 0.5 and 2.0 x LO6 cells / mL. In a. modality,. REP and / or the second expansion can be performed in 500 mL capacity gas permeable flasks with 100 cm gas permeable silicon bottoms (G-Rex 100, commercially available from Wilson Wolf Manufacturing Corporation, Kew Brighton, MR, USA). ), 5 x 10® or 10 x 10® TIL-can be grown with PBMCs in 400 mL of 50 / 50 medium, supplemented with 5% human AB serum, .3000 IU per mL IL-2 and 30 ng per mL of anti-CD3 (O'KT3). G-Rex 100 flasks can be incubated at 37°C in 5% C02 -On day 5, 250 mL of supernatant can be removed and placed in centrifuge bottles and centrifuged at 1500 rpm (491 x g) for 10 minutes. TIL pellets can be resuspended with 150 mL of fresh medium containing 5% human AB serum, 3000 IU per mL IL-2, and added back to the original 1.00 G-Rex flasks. When TILs are serially expanded in G-Rex 100 flasks, on day 7 the TIL in each G-Rex 100 can be suspended in the 300 mL medium present in each flask and the cell suspension can be divided into 3 aliquots. of 100 t which can be used to seed 3 G-Rex 100 flasks. Then 150 mL of AIM-V with 5% human AB serum and 3000 IU per mL of IL-2 can be added to each flask. G-Rex 100 flasks can be incubated at 37°C in 5% CO2 and after 4 days 150 mL of ADVI-V with 3000 IU per mL of IL-2 can be added to each G-RexlQO flask. Cells can be harvested on day 14 of culture. In one embodiment, REP and / or the second expansion is performed in flasks with the volume TILs being mixed with a 100- or 200-fold excess of inactivated feeder cells, 30 mg / mL anti-CD3 OKT3 antibody, and 3000 IU / mL. mL of IL-2 in 150 ml of medium. Replacement medium is made (generally 2 / 3 replacement medium by breathing with fresh medium) until the cells are transferred to an alternative growth chamber. Alternative growth chambers include GRex flasks and gas permeable containers as discussed more fully below. In one embodiment, REP and / or the second expansion is performed and further comprises a step where TILs are selected for tumor reactivity. higher. Any selection method known in the art can be used, for example, the methods described in Publication of US Patent Application No. 2016 / 0010058 Al, the disclosures of which are incorporated herein by reference, can be used to screen TILs for superior tumor reactivity. The REP and / or second TIL expansion can be performed using T-175 flasks and gas permeable bags as previously described (Tran KQ, Zhou J, Durflinger KH, et al., 2008, J Immunother., 31:742 -751, and Dudley ME, Wunderlich JR, Shelton TE, et al, 2003, J Immunother., 26:332-342) or gas permeable G-Rex flasks. In some modalities, REP and / or la is performed. second expansion using flasks. In some embodiments, REP is performed using gas permeable G-Rex flasks. For REP TIL and / or the second expansion in T-175 flasks, approximately 1 x .106 TIL is suspended in approximately 150 mL of medium and this is added to each T-175 flask. TILs are cultured with irradiated allogeneic PBMC (50 Gy) as "feeder" cells at a ratio of 1 to 100 and the cells are cultured in a 1:1 mixture of -CM medium and AIM-V (50 / 50 ratio). medium), supplemented with 3000 XU / mL of IL-2 and 30 ng / mL of anti-CD3. T-175 flasks are incubated at 37°C in 5% CO2. In some modes, the half of the medium is changed on day 5 using 50 / 50 medium with 3000 IU / mL IL-2. In some embodiments, on day 7, cells from 2 T-175 flasks are combined in a 3 L bag and AIM-V with 5% human AB serum and 3000 I'U / mL IL-2 are added. at 300 mL of TIL suspension. The number of cells in each bag can be counted every day or two and fresh medium can be added to keep the cell count between about 0.5 and about 2.0 x 10® cells / mL. For REP of TIL and / or the second expansion in 500 mL capacity flasks with 100 cm 2 gas-permeable silicon bottoms (G-RexlOO, Wilson Wolf), approximately 5 x 10® or 10 x 10® TIL are cultured with allogeneic PBMC irradiated at a ratio of 1 to 100 in 400 mL of 50 / 50 medium, supplemented with 3000 IU / mL IL-2 and 30 ng / mL anti-CD3. G-Rex 100 flasks are incubated at 37"C in 5% CO. In some embodiments, on day 5, 250mL of supernatant is removed and placed in centrifuge bottles and centrifuged at 1500rpm (491g) for 10 minutes. TIL pellets can then be resuspended with 150 mL of 50 / 50 fresh medium containing 3000 IU / mL IL-2 and added back to the original G-RexlOO flasks In modalities where TILs are serially expanded in G-Rex 100 flasks, on day 7 the TILs in each G-RexlOO are suspended in 300mL of medium present in each flask and the cell suspension is divided into three 100mL aliquots that are used to seed 3 G-Rex100 flasks.Then, 15Ό mL of AIM-V with 5% human AB serum and 3000 μL / mL of IL-2 is added to each flask.The G-Rex 100 flasks are incubated at 37°C for 5 % C02 and after 4 days 150 μL of AI.M-V with 3000 IU / mL of IL-2 is added to a given flask G-Re.xl00 Cells are harvested on day 14 of culture 1. Cells Al Carriers and Antigen-Presenting Cells In one embodiment, the second expansion procedures described herein (Stage D, including REP) require excess feeder cells during REP TIL expansion and / or during second expansion. In many embodiments, the feeder cells are peripheral blood mononuclear cells (PBMCs) obtained from standard whole blood units from healthy blood donors. PBMCs are obtained using standard methods such as Ficoll-Paque gradient separation. In general, allogeneic PBMCs are inactivated, either by irradiation or heat treatment, and used in REP procedures, as described in the Examples, in particular Example 14, which provides an exemplary protocol for evaluating 'Replication incompetence of irradiated allogeneic PBMCs. In some embodiments, PBMCs are considered replication-incompetent and accepted for use in the TIL expansion procedures described herein if the total number of viable cells at day 14 is less than the number of initial, viable cells in culture in on day 0 of the REP and / or day 0 of the second expansion (i.e. the start day of the second expansion). In some embodiments, PBMCs are considered replication-incompetent and accepted for use in the TIL expansion methods described herein if the total number of viable cells, cultured in the presence of OKT3. and IL-2, at day 7 and day 14 has not increased from the number of initial viable cells placed in culture at day 0 of the EPR and / or day 0 of the second expansion (i.e., the day of start of the second expansion). In some embodiments, PBMCs are cultured in the presence of 3-Ong / ml 0KT3 antibody and 3000 IU / ml IL-2. In some embodiments, PBMCs are considered replication incompetent and accepted for use in the TIL expansion procedures described herein if the total number of viable cells, cultured in the presence of OKT3 and IL-2, on day 7 and day 14 has not increased from the initial viable cell number put in. culture on day 0 of the REP and / or day 0 of the second expansion (ie, the start day of the second expansion). In some embodiments, PBMCs are cultured in the presence of 5-60 ng / ml. of OKT3 antibody and 1000-6'000 IU / ml IL-2. In some embodiments, PBMCs are cultured in the presence of 10-50 ng / ml OKT3 antibody and 0.200-5000 IU / ml IL-2. In some embodiments, PBMCs are cultured in the presence of 20-40 ng / ml OKT3 antibody and 2000-4000 IU / ml IL-2. In some embodiments, PBMCs are cultured in the presence of 25-35 ng / ml. ml of 0KT3 antibody and 2500-3500 lü / ml IL-2, In one embodiment, the artificial antigen presenting cells are used in the REP step as a replacement for, or in combination with, PBMCs. 2, Cytoin The expansion methods described herein generally use culture medium with high doses of a cytokine, in particular IL-2, as is known in the art. Alternatively, using combinations of cytokines for rapid expansion and / or second expansion of TILs is additionally possible, with combinations of two or more of IB-2, IL-15 and IL-21 as generally summarized in the 'Publication US Patent Application No. US 2017 / 0107490 Al, International Publication No. WO 2015 / 18935-6, US Patent Application Publication No. US 2017 / 0107490 .Al, and International Publication No. WO 2015 / 1893 57, each of which is hereby expressly incorporated by reference in its entirety. Thus, possible combinations include IL-2 and IL-15, IL-2 and IL-21, IL-15 and IL-2'Ι and IL-2, IL-15 and .IL-21, with the latter finding particular use in many modalities. The use of combinations of cytokines specifically promotes the generation of lymphocytes, and in particular T-cells can not be described herein. 3. Anti-CP 3 antibodies In some embodiments, the culture medium used in expansion methods described herein (including REP) also includes an anti-CD3 antibody. An anti-CD3 antibody in combination with IL-2 induces T cell activation and cell division in the TIL population. This effect can be seen with full-length antibodies as well as Fab and F1'ab' fragments, with the former being generally preferred; see, eg, Tsoukas et al., J. Immunal. 1985, 135, 1719, hereby incorporated by reference in its entirety. As will be appreciated by those in the art, there are a number of suitable anti-human CD3 antibodies that find use in the invention, including monoclonal and polyclonal anti-human CD3 antibodies from various mammals, including, but not limited to, marine, human, primate, rat, and canine antibodies. In particular embodiments, the anti-CD3 antibody O.KT3 (commercially available from Ortho~McNe.il, Raritan, NJ or Miltenyi Biotech, Auburn, CA) is used. E. STAGE E: Collection of TILs After the second expansion stage, the cells can be harvested. In some embodiments the TILs are collected after one, two, three, four or more second stage expansion. The TILs can be collected in any appropriate sterile container, including, for example, by centrifugation. Methods for collecting TILs are well known in the art. technique and any such known methods may be employed with the present process. In some embodiments, TILs are collected using an automated system. In some embodiments, TILs are collected using a semi-automated system. In some embodiments, TILs are collected using a semi-automated system. In some embodiments, the TILs of the second expansion are collected using a semi-automated machine. In some embodiments, the LOVO system is employed (commercially available from Benchmark Electronics, for example). In some embodiments, the harvesting step includes washing the TILs, formulating the TILs, and / or aliquoting the TILs. In some embodiments, the cells are optionally frozen after harvest or as part of the harvest. F. STAGE F: Final Formulation / Transfer to Infusion Bag After Steps A through E are complete, the cells are transferred to. a container for use in administration to a patient. In one embodiment, the TILs expanded using APCs of the present disclosure are administered to a patient as a pharmaceutical composition. In one embodiment, the pharmaceutical composition is a suspension of TILs in sterile buffer. TILs expanded using PBMCs of the present disclosure may be administered by any suitable route as is known in the art. In some embodiments, the T cells are administered as a single intravenous or intra-arterial infusion, which preferably lasts about 30 to 60 minutes. Other suitable routes of administration include intraperitoneal, intrathecal, and intralymphatic. G, Expansion stages, additional As will be appreciated, any of the steps A through F described above may be repeated any number of times and may, furthermore, be conducted in different orders than those described above. In some embodiments, one or more of the expansion steps may be repeated prior to Final Formulation Stage F. Such additional expansion steps may include the first- and / or second-stage expansion elements described above (for example, include the components described in cell culture medium). Additional expansion steps may further include additional elements: including additional components in the cell culture medium that are supplemented into the cell culture medium before and / or during the addition of additional expansion steps. In additional embodiments, any of the expansion steps described in Figure 23. and in the preceding paragraphs may be preceded or followed by a cryopreservation step in which the steps produced during an expansion step are preserved using methods known in the art. technique for storage until needed for the remaining stages of the manuf'ac turation / expansion processes. Pharmaceutical Compositions, Dosages, and Dosing Regimens for TILs, MILs, and PBLs In one embodiment, the TILs expanded using methods of the present disclosure are administered to a patient as a pharmaceutical composition. In one embodiment, the pharmaceutical composition is a suspension of TILs in sterile buffer. TILs expanded using methods of the present disclosure can be administered by any suitable route known in the art. Preferably, the TILs are administered as a single intravenous or intra-arterial infusion, which preferably lasts from about 30 to 60 minutes. Other suitable routes of administration include intraperitoneal, intrathecal, and intralymphatic administration. Any suitable dose of TILs can be administered. Preferably, from about 2.3 x 1010 to about 13.7 x 1Q10 TILs are administered, with an average of about 7.8 x 1010 TILs, particularly if the cancer is a hematologic malignancy. In one embodiment, about 1.2x10° to about 4.3x1010 TILs are administered. In some embodiments, the number of TILs provided in the pharmaceutical compositions of the invention is -approximately 1x10®, 2x10", 3x10", 4x1.0", 5x10", 6X10", 7x10", 8X10", 9*10 ® , IxlO7, 2x107, 3x10 7, 4xl07, 5xl07, 6x10·, 7x107, SxlO7, 9x10 7, IxlO8, 2xl08, 3x10*, 4x10«, 5X10 8, 6xl08, 7x10«, 8x10®, .9x10®, .9x10® , 2x10®, 3x10®, 4xl0 3, 5x10®, 6x108 , 7x103, 8x10®, .9x1'0®, lxl0ls, 2X.1O10, 3xlO1&, 4x1010, SxlO10, 6x10ie, 7x10 1&', 8x1.010ia, 8x1.010 IxlO 11, 2X1011, 3xl021, 4Χ1011, 5X1011, 6'xl.O11, 7x10 11, 8x1011, 9X1011., 1X1.0 12, 2xlQ12, 3X1 O 12, 4xl012, 5X1012,1,2x101, 6x1 Q102 9X10 12, 1x1013, 2xl013, 3xlQ12, 4x1013, SxlO13, 6x10-, 7x1023, SxlO13, and 9x1013. In one embodiment, the number of TILs provided in the pharmaceutical compositions of the invention is in the range of 1x10« to SxlO6, 5x10« to IxlO7, 1x107 to 5x107, SxlO'7 to IxlO8, IxlO8 to 5X10®, 5x108 to 1x10 ®, 1x10® to 5x10®, 5x10® to IxlO10, IxlO10 to SxlO10, SxlO10 to IxlO11, 5x1011 to IxlO13, IxlO12 to 5X1012, and SxlO12 to 1x1013. In a. embodiment of the invention, the number of TILs provided in the pharmaceutical compositions of the invention is in the. range from about 4x10® to about 2.5x10®. In another embodiment, the number of TILs provided in the pharmaceutical compositions of the invention is. 9.5x10®. In another embodiment, the number of TILs provided in the pharmaceutical compositions of the invention is 4.1x10®. In another embodiment, the number of TILs provided in the pharmaceutical compositions of the invention is 2.2x1-O9. In one embodiment of the invention, the number of TILs provided in the pharmaceutical compositions of the invention ranges from about 0.1x109 to about 15-x109 TILs, from about 0.1x109 to about 1.5x109 TILs, from about 0.12x1 O 9 to about 12xl-09 TILs, from about 0.15x109 to about 11x1.09 TILs, from about 0.2x10® to about 10X103 TILs, from about 0.3x109 to about 9x109 TILs, from about 0.4x109 to about 8x109 TIL”, from about 0.5x10a to about 7x10® TILs, from about 0.6x109 to about 6x10® TILs, from about 0.7x10® to about 5x109 TILs, from about 0.8x10® to about 4x10 9 TILs, from about 0.9x1O9 to about 3x105 TILs, or from about 1x109 to about 2x109 TILs. In some embodiments, the concentration of the TILs provided in the pharmaceutical compositions of the invention is less than, for example, 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%. , 19%, 1.8%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 1.0%, 9%, 8%, 7%, 6%, 5%, 4%, 3 %, 2%, 1%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.09%, 0.08%, 0.07%, 0.06%, 0.05%, 0.04%, 0.03%, 0.02%, 0.01%, 0.009%, 0.008%, 0.007%, 0.006%, 0.005%, 0.004%, 0.003%', 0.00.2%, 0.001%, 0.0009%, 0.0008%, 0.0007%, 0.0006%, 0.0005%, 0.0004%, 0.0004% , 0.0002% or 0.0001% in p / p, p / v or v / v of the pharmaceutical composition. In some embodiments, the concentration of the TILs provided in the pharmaceutical compositions of the invention is greater than 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 19.75%, 19.50% , 19.25% 1.9%, 18.75%, 18.50%, 18.25% 18%, 17.75%, 17.50%, 17.25% 17%, 16.75%, 16.50%, 16.25% 16%, 15.7.5%, 15.50% , ,15.25% 15%, 14.75%, 14.50%, 14.25% 14%, 13.75%, 13.50%, 13.25% 13%, 12.75%, 12.50%, 1.2.25% 12%, 11.7.5%, 1.1 .50%, 11.25% 11%, 10.75%, 10.50%, 10.25% 10%, 9.75%, 9.50%, 9.25% 9%, 8.7.5%, 8.50%, 8.25% 8%, 7.75%, 7.5.0 %, 7.25% 7%, 6.75%, 6.50%, 6.25% 6%, 5.75%, 5.50%, 5.25% 5%, 4.75%, 4.50%, 4.25%, 4%, 3.75%, 3.50%, 3.25 %, 3%, 2.75%, 2.50%', 2.25%, 2%, 1.75%, 1.50%, 125%, 1%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.09%, 0.08 %, 0.07%, 0.06%, 0.05%, 0.04%, 0.03%, ϋ.02%, 0.01%, 0.009%, 0.008%, 0.007%, 0.00.6%, 0.005%, 0.004%, 0.003% w / w, w / 'v, or v / v of the composition . pharmaceutical. In some embodiments, the concentration of the TILs provided in the pharmaceutical compositions of the invention ranges from about 0.0001% to about 50%, about 0.001% to about 40%, about 0.01% to about 30% , about 0.02% to about 29%, about 0.03% to about 28%, about 0.04% to about 27%, about 0.05% to about 26%, about-0.06% to about 25%, about 0.07% to about 24%, about- 0 - 08% up to about 2.3%, about 0.09% up to about 22%, about 0.1-% up to about 21%, about 0.2% up to about 20%, about 0.3% up to about 19%, about .0.4 % to about 18%, about 0.5% to about 17%, about 0.6% to about 16%, about and 0.7% to about 15%, about 0.8% to about 14%, about 0.9% to about 12% or about 1% to about 10% by w / w, w / v or v / v of the pharmaceutical composition. In some embodiments, the concentration of the TILs provided in the pharmaceutical compositions of the invention ranges from about 0.001% to about 10%, about 0.01% to about 5%, about 0.02% to about 4.5%, about 0.03% up to about 4%, about 0.04% to about 3.5%, about 0.0.5% to about 3%, about 0.06% to about 2.5%, about 0.0.7% to about 2%, about. 0.08% to about 1.5%, about 0.09% to about 1%, about 0.1% to about 0.9% w / w, w / v or v / v of the pharmaceutical composition. In some embodiments, the amount of the TILs provided in the pharmaceutical compositions of the invention is equal to or less than 1.0 g, 9.5 g, 9.0 g, 8.5 g, 8.0 g, 7.5 g, 7.0 g, 6.5 g, 6.0g, 5.5g, 5.0g, 4.5g, 4.0g, 3.5g, 3.0g, 2.5g, 2.0g, 1.5g, 1.0g, 0.95g, 0.9g, 0.85g, 0.8g, 0.75g, 0.7g, 0.65g, 0.6g, 0.55g, 0.5g, 0.45g, 0.4g, 0.35g, 0.3g, 0.25g, 0.2g, 0.1.5g, 0.1g, 0.0.9 g, 0.08' g, 0.07 g, 0.06 g, 0.05 g, 0.04 g, 0.03 g, 0.02 g, 0.01 g, 0.009 g, 0.008 g, 0.007 g, 0.006 g, 0.005 g, 0.004 g, 0.003 g, 0.002 g , 0.001 g, 0.0009 g, 0.0008 g, 0.0007 g, 0.0006 g, 0.00Ό5 g, 0.0004 g, 0.0003 g, 0.0002 g, or 0.0001 g. In some embodiments, the amount of the TILs provided in the pharmaceutical compositions of the invention is more than 0.0001 g, 0.0002 g, 0.0003 g, 0.0004 g, 0.0005 g, 0.0006 g, 0.0007 g, 0.0008 g, 0.0009 g, 0.001 g, 0.0015 g, 0.0.02 g, 0.0025 g> 0-003 g, 0.0035 g, 0.004 g, 0.0045 g, 0.005 g, 0.0'055 g, 0.006 g, 0.0065 g, 0.007 g> 0.0075 g, 0.008 g, 0.0085g, 0.009g, 0.0095g, 0.01g, 0.015g, 0.02g, 0.025g, 0.03g, 0.035g, 0.04g, 0.045g, 0.05g, 0.055g, 0.06g, 0.065g, 0.07g, 5g , 0.08g, 0.085g, 0.09g, 0.095g, 0.1g, 0.15g, 0.2g, 0.25g, 0.3g, 0.35g, 0.4g, 0.45g, 0.5g, 0.55g, 0..6g, 0.65 g, 0.7 g, 0.75 g,. 0.8g, 0>85g, 0.9g, 0.95g. 1g, 1.5g, 2g, 2.5, 3g, 3.5, 4g, 4.5g, sg, 5.5g, 6g, 6.5g, 7g, 7.5g, 8g, 8.5g , 9g, 9.5g, or 10g. The TILs provided in the pharmaceutical compositions of the invention are effective over a wide dosage range. The exact dosage will depend on the route of administration, the form in which the compound is administered, the gender and age of the subject to be treated, the body weight of the subject to be treated, and the preference and experience of the attending specialist. Clinically established dosages of TILs may also be used if appropriate. Amounts of pharmaceutical compositions administered using the methods herein, such as dosages of TILs, will be dependent on the human or mammal to be treated, the severity of the disorder or condition, the rate of administration, the arrangement of ingredients pharmacists' assets and the discretion of the prescribing specialist. In some embodiments, the TILs can be administered in a single dose. Such administration may be by injection, for example intravenous injection. In some embodiments, TILs can be administered in multiple doses. The dosage can be once, twice, three times, four times, five times, six times, or more than six times per year. Dosing can be once a month, once every two weeks, once a week, or once every other day. TIL management can continue at 1.as needed. In some modalities, an effective dosage of TILs is approximately 1x106, 2x10®, 3x105, 4x10", 5x1.0", 6x106, 7x10", 8x10", 9x10", 1x10'7, 2x10", 3x10 7, 4X107, 5X10?, 6xl07, 7X107', 8xl07, 9X107., 1x10«, 2xlO8, 3x10®, 4X1Q ®, 4x109., 5x10®, 6X1 O®, 7x109, 8x109, 9x10®, .1x1010, 2x10", 3x10"., 4x10"', 5x10", 6x10", 7x1010,. 8X10", 9x10", 1x10", .2x10" > 3x10", 4x10", 5x10", 6x10", 7X1.0", 8x10", 9x10", 1X10", 2x10", 3xl012, 4x1012, SxlO12, 6x10 ", 7x10", 8x10", '9x10", 1x10", 2x10", 3x10", 4x10", 5x10", 6x10", 7x10", 8x10", and 9x10'". In some embodiments, an effective dosage of TILs is in the range of 1x106' to 5x10s, 5x10® to 1x107, 1X107 to SxlO7, SxlO7 to lxlOs, 1X10® to 5x10®, 5x10® to IxlO9, 1x109 to SxlO9, 5x10® up to 1x1010., 1x10" up to SxlO88, 5x10" up to .1x10", SxlO81 up to 1x10", 1x10" up to 5x10", and SxlO12 up to 1x1013. In one embodiment of the invention, the clinical dose of MILs useful for patients with acute myeloid leukemia (AML) ranges from about 4x10® to about 2.5x10® MILs. In another embodiment, the number of MILS provided in the pharmaceutical compositions of the invention is 9.5x10® MILs. In another embodiment, the number of MILs provided in the pharmaceutical compositions of the invention is 4.1x10®. In another embodiment, the number of MILs provided in the pharmaceutical compositions of the invention is 2.2x10®. In some embodiments, an effective dosage of TILs is in the range of about 0.01 mg / kg to about 4.3 mg / kg, about 0.15 mg / kg to about 3.6 mg / kg, about 0.3 mg / kg to about 3.2 mg / kg. kg, about 0.35 mg / kg to about 2.85 mg / kg, about 0.15 mg / kg to about 2.85 mg / kg, about 0.3 mg to about: 2.15 mg / kg, about 0.45 mg / kg to about 1.7 mg / kg, about 0.15 mg / kg to about 1.3 mg / kg, about. 0.3 mg / kg to about 1.15 mg / kg, about 0.45 -mg / kg to about. 1 mg / kg, about 0.55 mg / kg to about 0.85 mg / kg, about 0.65 mg / kg to about 0.8 mg / kg, about 0.7 mg / kg to about 0.75 mg / kg, about 0.7 mg / kg to about 2.15 mg / kg, about 0.85 mg / kg to about- .2 mg / kg, about 1 mg / kg to about 1.85 mg / kg, about 1.15 mg / kg to about 1.7 mg / kg, about 1.3 mg / kg mg to about 1.6 mg / kg, about 1.35 mg / kg to about 1.5 mg / kg, about 2.15 mg / kg to about 3.6 mg / kg, about 2.3 mg / kg to about 3.4 mg / kg, about 2.4 mg / kg to approx. 3.3 mg / kg,- about 2.-6 mg / kg up to about 3.15 mg / kg, about 2.7 mg / kg up to about 3 mg / kg-, about 2.8 mg / kg up to about 3 mg / kg, or about 2.85 mg / kg to about 2.95 mg / kg. In some embodiments, my effective dosage of TILs is in the range of about 1 mg to about 500 mg, about 10 mg to about 300 mg, about 20 mg to about 250 mg, about 25 mg to about 200 mg, about 1 mg. mg to about 50 mg, about 5 mg to about 45 mg, about 10 mg to about 4 0 mg, about 15 mg to about 35 mg, about 20 mg to about 3 0 mg, about 23 mg to about 28 mg, about 5 0 mg to about 150 mg, about 60 mg to about 140 mg, about 70 mg to about 130 mg, about 80 mg to about 120 mg, about 90 mg to about 110 mg, or about 95 mg to about 105 mg, about 98' mg to about 102 mg, about 150 mg to about approximately 250 mg, about .160 mg to about 240 mg, about 170 mg to about 230 mg, about 180 mg to about 220 mg, about 190 mg to about 210 mg, about .195 mg to about 205 mg, or about 198 to about 207 mg. An effective amount of the TILs can be administered in either single or multiple doses by any of the accepted modes of administration of agents that have similar utilities, including intranasal and transdermal routes, by intra-arterial injection, intravenously, intraperipherally. tonally, parenterally, intramuscularly, subcutaneously, topically, by transplantation or direct injection into the tumor, or by inhalation. Methods to Treat Cancer The compositions and combinations of TILs, PBLs, and / or MILs (and populations thereof) described above can be used in a method of treating hyperproliferative disorders. In a preferred embodiment, they are for use in the treatment of cancers. In a preferred embodiment, the invention provides a method of treating a cancer, wherein the cancer is a hematologic malignancy, such as a liquid tumor. In a preferred embodiment, the invention provides a method of treating a cancer, wherein the cancer is a hematologic neoplasm selected from the group consisting of acute myeloid leukemia (AML), mantle cell lymphoma (MCL), follicular lymphoma (EL), Diffuse Large B-Cell Lymphoma (DLBCL), Activated B-Cell DLBCL (ABC), Germinal Central B-Cell (GCB) DLBCL, Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Leukemia (SIL), Non-Hodgkin's Lymphoma (NHL), Hodgkin's lymphoma, relapsed and / or refractory Hodgkin's lymphoma, acute B-cell lymphoblastic lymphoma (B-ALL), mature B--ALL, Burkitt's lymphoma, Waldenstrom's macroglobulinemia (W), multiple myeloma, myelodysplastic syndromes, myelofibrosis, chronic myelocytic leukemia, follicular center lymphoma, indolent NHL, human immunodeficiency virus-associated B-cell lymphoma. (HIV), and Epstein-Barr virus (EBV)-associated B-cell lymphoma. In. In one embodiment, the invention provides a method of treating a cancer, wherein the cancer is a hematologic malignancy responsive to PD-1 and / or PD-L1 inhibitor therapy including pembrolisumab, nivolumab, durvalumab, avelumab, or ate -zolizumab. In one embodiment, the 1st invention provides a method of treating a cancer with a population of tumor-infiltrating lymphocytes (TILs) comprising the steps of; (a) obtaining a tumor from a patient by resection, biopsy, needle aspiration, or apheresis, the tumor comprising a first population of TILs; (b) optionally fragmenting or dissociating the tumor to obtain tumor fragments and contacting tumor fragments with a first cell culture medium; (c) performing an initial expansion of the first population of TILs in the first cell culture medium to obtain a second population of TILs, wherein the second population of TILs is at least 5-fold greater in number than the first population of. TILs, wherein the first cell culture medium comprises IL-2; (d) performing a second expansion of the second population of TILs in a second cell culture medium to obtain a third population of TILs, wherein the third population of TILs is at least 50-fold greater in number than the second population of TILs after 7 days from the start of the second expansion; wherein the second cell culture medium comprises IL-2-, OKT-3 (anti--CD3 antibody), and irradiated allogeneic peripheral blood mononuclear cells (PBMCs); and wherein the second expansion is carried out over a period of 14 days or less; (e) harvesting the. third population of TILs; and (f) administering a therapeutically-effective portion of the third population of TILs to a patient with the cancer; wherein the tumor is a liquid tumor, and wherein the cancer is a hematologic malignancy. In one embodiment, the invention provides a method of treating a cancer with a population of tumor infiltrating lymphocytes (TILs) comprising the steps of: (a) obtaining a tumor from a patient by resection, biopsy, needle aspiration needle, or apheresis, the tumor comprising a first population of TILs; (b) optionally fragmenting or dissociating the tumor to obtain tumor fragments and contacting the tumor fragments with a first cell culture medium; (c) performing a initial expansion of the first population of TILs in the first cell culture medium to obtain a second population of TILs, wherein the second population of TILs is at least 5-fold greater in number than the first population of TILs, wherein the first cell culture medium comprises IL-2; (d) performing a second expansion of the second population of TILs in a second cell culture medium to obtain a third population of TILs, wherein the third population of TILs is at least 50 -times greater in number than the second population of TILs after 7 days from the start of the. second expansion; wherein the second cell culture medium comprises IL-2, OKT-3 (anti-CD3 antibody), and irradiated allogeneic peripheral blood mononuclear cells (PBMCs); and wherein the second expansion is performed over a period of 14 days or less; (e) collecting the third population of TILs; and (f) administering a therapeutically effective portion of the third population of TILs to a patient with the cancer; wherein the tumor is a liquid tumor, and wherein the cancer is a neoplasm. hematology selected a. from the group consisting of acute myeloid leukemia (AML), mantle cell lymphoma (MCL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), DLBCL activated B-cell (ABC), DLBCL B-cell Germinal central leukemia (GCB), chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), non-Hodgkin's lymphoma (WL), Hodgkin's lymphoma, relapsed and / or refractory Hodgkin's lymphoma, B-cell acute lymphoblastic lymphoma (B- ALL), mature B-ALL, Burkitt lymphoma, Wáldehstrom's macroglobulinemia (WM), multiple myeloma, myelodysplastic syndromes, myelofibrosis, chronic myelocytic leukemia, follicular center lymphoma, indolent NHL, human immunodeficiency virus-associated B-cell lymphoma (.HIV), and Epstein-Barr virus (EBV)-associated B-cell lymphoma. In one embodiment, the invention provides a method of treating a cancer with a population of tumor infiltrating lymphocytes (TILs) comprising the steps of: (a) pre-treating a patient with a regimen comprising an inhibitor kinase or an ITK inhibitor; (b) obtaining a tumor from a patient by resection, hyoppsy, needle aspiration, or apheresis, the tumor comprising a first population of TILs; (c) optionally fragmenting or dissociating the turnar to obtain tumor fragments and contacting the tumor fragments with a first cell culture medium; (d) performing an initial expansion of the first population of TILs in the first cell culture medium to obtain a second population of TILs, wherein the second population of TILs is at least 5 times greater in number than the first population of TILs, wherein the first cell culture medium comprises IL-2; (e) performing a second expansion of the second population of TILs in a second cell culture medium to obtain a third population of TILs, where the third population of. TILs is at least 50-fold greater in number than the second population of TILs after 7 days from the start of thesecond expansion; wherein the second cell culture medium comprises IL-2, OKT-3 (anti-CD3 antibody), and irradiated allogeneic peripheral blood mononuclear cells (PBMCs) and wherein the second expansion is performed for a period of 14 days or less ;(f) collect the third population of TILs; and (g) administering a therapeutically effective portion of the third population of TILs to a patient with the cancer; wherein the tumor is a liquid tumor, and wherein the cancer is a hematologic malignancy. In one embodiment, the invention provides a method of treating a cancer with a population of tumor-infiltrating lymphocytes (TILs) comprising the steps of: (a) pre-treating a patient with a regimen comprising a kinase inhibitor or an ITK inhibitor; (b) obtaining a tumor from a patient by resection, biopsy, needle aspiration, or apheresis, the tumor comprising a first population of TILs; (c) optionally fragmenting or dissociating the tumor to obtain fragments tumor and contacting the tumor fragments with a first cell culture medium; (d) performing an initial expansion of the first population of TILs in the first cell culture medium to obtain a second population of TILs, wherein the second population of TILs is at least 5-fold greater in number than the first population of TILs, wherein the first cell culture medium comprises IL-2; (e) performing a second expansion of. the second population of TILs in a second cell culture medium to obtain a third population of TILs, wherein the third population of TILs is at least 50-fold greater in number than the 1st second population of TILs after 7 days a from the start of the second expansion; wherein the second cell culture medium comprises IL-2, OKT-3 (anti-CD3 antibody), and irradiated allogeneic peripheral blood mononuclear cells (PBMCs); and wherein the second expansion is performed over a period of 14 days or less,- (f) collecting the third population of TILs; and (g) administering a therapeutically effective portion of the third population of TILs to a patient - with the cancer; wherein the tumor is a liquid tumor, and wherein the cancer is a hematologic malignancy selected from the group consisting of acute myeloid leukemia (AML), mantle cell lymphoma (MCL.), follicular lymphoma (EL), lymphoma of Diffuse Large B-Cell (DLBCL), Activated B-Cell (ABC) DLBCL, Germinal Central B-Cell (GCB) DLBCL, Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Leukemia (SLL), Non-Hodgkin's Lymphoma (NHL), Hodgkin's, relapsed and / or refractory Hodgkin's lymphoma, mature B-cell acute lymphoblastic lymphoma (B-AliL) and B-ALL, Burkitt's lymphoma, Waldenstrom's macroglobulinemia (WM), multiple myeloma, myelodysplastic syndromes, myelofibrosis, chronic myelocytic leukemia , follicular center lymphoma, indolent NHL, human immunodeficiency virus (HIV)-associated B-cell lymphoma, and Epstein-Barr virus (EBV)-associated B-cell lymphoma In one embodiment of the invention, TILs are expanded using MIL Method 1 and administered to a patient in accordance with the present invention. In one embodiment of the invention, TILs are expanded using MIL Method 2 and administered to a patient in accordance with the present invention to treat cancer. In one embodiment of the invention, TILs are expanded using MIL Method 3 and administered to a patient in accordance with the present invention to treat cancer. In one embodiment of the invention, TILs expanded using MIL Method 1, MIL Method 2, or MIL Method 3 are administered to a patient in accordance with the present invention to treat AML. In one embodiment of the invention, TILs are expanded using PBL Method 2 and administered to a patient in accordance with 1st present invention to treat cancer. In one embodiment of the invention, TILs are expanded using PBL Method 2 and administered to a patient in accordance with the present invention to treat cancer. In one embodiment of the invention, TILs are expanded using PBL Method 2 and administered to a patient in accordance with the present invention to treat cancer. In one embodiment of the invention, the expanded TILs using PBL Method 1, el. PBL Method 2, or PBL Method 3 are administered to a patient in accordance with the present invention to treat CLL. In any of the above embodiments of the invention, pre-treatment with a kinase inhibitor is described. In one embodiment, the kinase inhibitor is selected from the group consisting of itnatinib, dasatinib, ibrutinib, bosutinib, nilotinib, erlotinib, or other kinase inhibitors, tyrosine kinase inhibitors, or -serine / threonine kinase inhibitors known in the art. The technique. In one embodiment, kinase inhibitor pre-treatment regimens are as known in the art and / or as prescribed by one of skill. In any of the above embodiments of the invention, pre-treatment with an inhibitor of IL-2 inducible I cell kinase (ITK) is described. Interleukin-inducible T-cell kinase (ITK) is a non-receptor tyrosine kinase expressed on T cells and regulates several pathways. Any of the ITK inhibitors known in the art can be used in embodiments of the present invention (see, eg, Lo, et al., Expert Opinion on Therapeutic Patents, 20:459-469 (2010); Vargas, et. by reference herein in its entirety). In one embodiment of the invention, the ITK inhibitor is a covalent ITK inhibitor that covalently and irreversibly binds ITK. In one embodiment of the invention, the ITK inhibitor is an ITK-binding allosteric ITK inhibitor. In one embodiment of the invention, the ITK inhibitor is selected from the group consisting of am.inothiaz.ol-based ITK inhibitors, 5-aminomethylbenzimidazole-based ITK inhibitors, 3- aminopyrid-2-ones, (4 or 5~ aryl)pyrazolyl-indole-based ITL inhibitors, benzimidazole-based ITK inhibitors, arninobenzimidazole-based ITK inhibitors, aminopyridine-based ITK inhibitors, ITK inhibitors based on aminopyridine, ITK inhibitors based on diazolodiazine, ITK inhibitors based on triazole, ITK inhibitors based on S-aminopyrido-P-ones, ITK inhibitors based on indolylindazole, ITK inhibitors based on of indole, ITK inhibitors a. aza-indole-based inhibitors, pyrazolyl-indole-based inhibitors, thienopyrazole-based ITK inhibitors, heterocyclic ITK inhibitors, and ITK inhibitors targeting cysterna-442 in the ATP pocket (such as ibrutinib), ITK inhibitors a aza-benzimidazole-based, benzothiazole-based ITK inhibitors, indole-based ITK inhibitors, pyridone-based ITK inhibitors, sulfoximine-substituted pyrimidine ITK inhibitors, -arylpyridinone-based ITK inhibitors, and any from other inhibitors known in the art. In one embodiment of the invention, ITK inhibitor pretreatment regimens are as known in the art and / or as prescribed by one of skill. In one embodiment of the invention, the ITK inhibitor is selected from the group consisting of: and combinations thereof. In one embodiment of the invention, the ITK inhibitor is selected from the group consisting of imatinib, dasat.inib (BMS-354825), Sprycel [N-(2~chloro-6~methylphenyl)-2-(6- (4- (2~hydroxyethyl) -p iper a z in 1 - i 1) - 2 - me t - i Ipyr imidin-4.- i 1 amino) thiazole - 5 -carboxamide) , ibrutinib ( (l -{ (3R) -3- [4~.amino-3- (4- phenoxy i f en i 1) - .1H - p i r a zolo [ 3,4 - d ] p i r i m i d i η -1 - i 1 ] p i pe r i d i η -1 - 11 J-prop-2-en- 1-one), bosutinib, nilotinib, erlotinib, 1H-pyrazolo[4,3-c]cinolin-3-ol, CTA056 (743enzil-1-(3- (piperidin-l-yl)propyl)-2-- (4- (pyridin~4-yl)phenyl)-1H-imidazo[4.5-g]quinoxalin-6(5H)-one), Compound 10 (Boehringer Ingelhe.im de Mori.arty, et al., Bioorg Med Chem Lett, 18:5537--40 (2008)), Compound 19 (Boehringer Ingelheim de Moriarty, et al., Bioorg Med Chem Lett., 18:5537-40 (2008) ), Compound 27 (Boehringer Ingelheim de Mori.arty, et al., Bioorg Med Chem Lett., 18:5537-40 (2008) ) , Compound 2'6' (Boehringer Ingelheim de -Winters, et al., Bioorg Med Chem Lett., 18:5541-4. (2008)), Compound 37 (Boehringer Ingelheim de Cook, et al., Bio.org Med Chem Lett, 19:773-7 (2009)), Compound 41. (Boehringer Ingelheim de Cook, et al., Bioorg Med Chem Lett., 19:773-7 (2009)), Compound 48 (Boehringer Ingelheim de Cook, et al, Bioorg Med Chem Lett., 19:773-7 (2009)), Compound 51 (Boehringer Ingelheim from Cook, et al., Bioorg Med Chem Lett., 19:773-7 (2009)) , Compound 10η (Boehringer Ingelheim de Riete, et al., Bioorg Med. Chem Lett., 19:1588-91 (.2009)), Compound- 1.0o (Boehringer Ingelheim de Riete, et al., Bioorg Med Chem Lett ., 19:1588-91 (2009)), Compound 7v (Vertex de Charrier, et al., J Med Chem,, 54:2341-50 (2011)), Compound 7w (Vertex de Charrier, et al., J Med Chem., 54:2341-.50 (2011)), Compound 7x (V ertex de Charrier, et al., J Med Chem., '54:2341-50 (2011)), Compound 7y (Vertex de Charrier, et al., J Med Chem., '54:2341-50 (201.1) ), Compound 44 (Bayer Schering Pharroa de vonBonin, et al., Exp Dezmatol -, 20:41-7 (2011)), Compound 13 (Nycomed de Velankar, et al., Bioorg Med Chem., 18:4547-59 (2010)), Compound 24 (Nyeomed of Velankar, et al., Bioorg Med Chem., 18:4547-59 (2010)), Compound 34 (Nyeomed de Velankar, et al., Bioorg Med Chem., 18:4547-59 (2010) ), Compound 10o (Nyeomed de Herdemann, et al,, Bioorg -Méd Chem Let-t., 21:1852- 6 (2011)), Compound 3 (Sanofi US by Me Lean, et al., Biooxg Med Chem Lett., 22:329-6-300(2012)), Compound 7 (Sanofi US by McLean, et al., Bioorg Méd Chem Lett., 22:3296-300 (2012), and / or or other kinase inhibitors, tyrosine kinase inhibitors, or serine / threonine kinase inhibitors known in the art, as well as any of the combinations of ipgs themselves . In any of the above embodiments, pre-treatment regimens comprising ibrutinib (commercially available as IMBRUVICA, and which has the chemical name 1-[(3R)-3-[4-amino-3-(4-phenoxyfeni. l) -1H-pyrazolo [.3,4-d]pyrimidin-l-yl] -1-p.iperidinil] -2-pr.open-l-one) may include orally administering a 140 mg q.d. capsule, administering orally two capsules of 140 mg q.d., or orally administer four capsules of 140 mg q.d., for a duration of approximately one day, two days, three days, four days, five days, six days, seven days, eight days, nine days, ten days, eleven days, twelve days, two weeks, three weeks, one month, two months, three months, four months, five months, or six months. In the above embodiments, pre-treatment regimens comprising ibrutinib may also comprise orally administering a dose of ibrutinib selected from the group consisting of 25 mg, 5.0 mg, 75 mg, 100 mg, 125 mg, 150mg, 175mg, 200-mg, 225mg, 250mg, 275mg, 300mg, 325mg, 350mg, 375mg, 400mg. 425 mg, 450 mg, and 500 mg, wherein administration occurs once daily, twice daily, three times daily, or four times daily, and wherein the duration of administration is selected from the group consisting of approximately one day, two days, three days, four days, five days, six days, seven days, eight days, nine days, ten days, eleven days, twelve days, two weeks, three weeks, one month, two months, three months , four months, five months, and six months. In any of the above modalities, the cancer to be treated is a hematologic malignancy selected from the group consisting of acute myeloid leukemia (AML), mantle cell lymphoma (MCL), follicular lymphoma (FL), large B-cell lymphoma (DLBCL), Activated B-Cell DLBCL (ABC), Germinal Central B-Cell (GCB) DLBCL, Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Leukemia (SLL), Non-Hodgkin's Lymphoma (NHL), Hodgkin's Lymphoma, Relapsed and / or refractory Hodkin's lymphoma, leukemia, B-cell acute elastic lymphoma (B-ALL), mature B-ALL, Burkitt's lymphoma, Waldenstrom's macroglobulinemia (WM), multiple myeloma, myelodysplastic syndromes, myelofibrosis, chronic myelocytic leukemia , follicular center lymphoma, indolent NHL, human immunodeficiency virus (HIV)-associated B-cell lymphoma, and Epstein virus-associated B-cell lymphoma- Barr (EBV!, The efficacy of the methods and compositions described herein to treat, prevent and / or manage the indicated diseases or disorders can be tested using various animal models known in the art, Non Myeloablative Lymphadenopathy_ with Chemotherapy In one embodiment, the invention provides a method of treating a cancer with a population of TILs, wherein a patient is pre-treated with non-myeloablative chemotherapy prior to an infusion of TILs in accordance with the present disclosure. In one embodiment, the non-myeloablative chemotherapy is one or more chemotherapeutic agents. In one modality, non-mxeloablative chemotherapy is cyclophosphamide 60 mg / kg / d for 2 days (days 27 and 26 prior to TIL infusion) and fludarabine 25 mg / m2 / d for 5 days (days 27 to 23 prior to infusion). to TIL infusion), In one embodiment, after non-myeloablative chemotherapy and TIL infusion (on day 0) according to the present description, the patient receives intravenous infusion of IL-2 intravenously at 720,000 IU / kg every 8 hours for physiological tolerance. Experimental findings indicate that lymphodepletion prior to adoptive transfer of tumor-specific T cells plays a key role in enhancing treatment efficacy by eliminating regulatory T cells and competing elements of the immune system ("cytokine depression"). Accordingly, some embodiments of the invention utilize a lymphodepletion step (sometimes also referred to as "immunosuppressive conditioning") in the patient prior to the introduction of the TILs of the invention. In general, lymphodepletion is achieved using administration of fludarabine or cyclophosphamide (the active form is referred to as maphosphamide) and combinations thereof. Such methods are described in Gassner, et al., Cancer Immunol. Tmmother. 2011, 60, 75-8.5, Muranski, et al., Nat. Clin. Pract. Oncol, 2006, 3, 668-681, Dudley, et al., J. Clin. Oncol. 2008, 26, 5233-5239, and Dudley, et al., J. Clin. Oncol 2005, 23, 2346-2357, all of which are incorporated by reference herein in their entireties. In some embodiments, fludarabine is administered at a concentration of 0.5 ug / mL-10 pg / mL fludarabine. In some embodiments, fludarabine is administered at a concentration of 1 pg / mL fludarabine. In some modalities, fludarabine treatment is administered for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days or more. In some embodiments, fludarabine is administered to one. dosage of 10 mg / kg / day, 15 mg / kg / day, 20 mg / kg / day, 25 mg / kg / day, 30 mg / kg / day, 35 mg / kg / day, 40 mg / kg / day, or 45 mg / kg / day. In some modalities, fludarabine treatment is administered for 2-7 days at 35 mg / kg / day. In some modalities, fludarabine treatment is given for 4-5 days at 35 mg / kg / day. .In some modalities, fludarabine treatment is administered for 4-5 days at 25 mg / kg / day. In some embodiments, maphosphamide, the active form of cyclophosphamide, is obtained at a concentration of 0.5 ug / mL-10 pg / mL by administration of cyclophosphamide. In some embodiments, maphosphamide, the active form of cyclophosphamide, is obtained at a concentration of 1 µg / mL by administration of cyclophosphamide. In some embodiments, cyclophosphamide treatment is administered for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days or more. In some embodiments, cyclophosphamide is administered at a dosage of ICO mg / m2 / day, 150 mg / m2 / day, 175 mg / m2 / day, 200 mg / m2 / day, 225 mg / m2 / day, 250 mg / m2 / day. m2 / day., 275 mg / m2 / day, or 300 mg / m2 / day. In some modalities, cyclophosphamide is administered intravenously (i.e. i.v.). In some modalities, cyclophosphamide treatment is administered for 2-7 days at 3-5 mg / kg / day. In some modalities, cyclophosphamide treatment is administered for 4-5 days at 250 mg' / m2- / day i.v. In. some- modalities, cyclophosphamide treatment is administered for 4 days at 2SO mg / m2 / day i.v. In some embodiments, lymphatic depletion is accomplished by administering fludarabine and cyclophosphamide together to a patient. In some modalities, fludarabine is administered at 25 mg / m2 / day i.v. and cyclophosphamide is given at 250 mg / mVday i.v. for 4 days. In one embodiment, lymphaticization is accomplished by administration of cyclophosphamide at a dose of 50 mg / m2 / day for two days, followed by administration of fludarabine at a dose of 25 mg / m2 / day for five days. Various methods for expanding TILs obtained from bone marrow or peripheral blood are described in present 1.a. In one embodiment of the invention, the. Lymphatic depletion is accomplished by administration of cyclophosphamide at a dose of 60 mg / m2 / day for two days followed by administration of fludarabine at a dose of 2.5 mg / m2 / day for five days. Various methods for expanding TILs obtained from bone marrow or peripheral blood are described herein. EXAMPLES Embodiments encompassed herein are now described with reference to the following examples. These examples are provided for the purposes of illustration only and the description herein encompassed should in no way be construed as limiting these examples, but preferably, should be construed to encompass any and all variations which will become apparent as a result of the teachings provided herein. Example 1 - Expansion of TILs from Non-Hodgkins Lymphoma TILs were expanded from five non-Hodgkin lymphoma tumors (one mantle cell lymphoma tumor, three follicular lymphoma tumors, and one ABC-type diffuse large B-cell lymphoma tumor) with the pathologies given in Figure 1, using IL-2 for 11 to 14 days in a pre-REP stage, followed by subsequent REP for 14 days using IL-2, mitogenic anti-CD3 antibody, and irradiated allogeneic peripheral blood mononuclear cell (PBMC) feeder cells. TILs were excessively generated from all 5 lymphoma tumors with a maximal expansion rate of 680-fold, significantly higher than previously observed using other methods. Schwart-zentruber, et al., Blood 1993, 82, 1204-1211. Furthermore, the median CD3* T cell population was 95% (versus 75% using the method of Schwartzentruber, et al., Blaoá 1993, 82, 1204-1211). Cell sorting and flow cytometry were performed using a Becton, Dickinson & Co. (BD) FACS CANTO II system. A marked relative increase in effector memory cells that was comparable to that in melanoma TILs was observed by flow cytometric analysis (Figure .2). A significant increase in CD45R?V effector memory cells (TEMRA) (p~0.001 .3; CD4, CD-8) and CD28+CD4+ subsets (p~0.008) was observed in lymphoma compared to TIL from melanoma cultures (Figure 3). Comparisons of phenotypic markers of T cell differentiation into CD4* and CD8* subsets are shown in Figure 4 and Figure 5, respectively. Comparisons of phenotypic markers of T cell depletion in CD4+ and CD8* subsets are shown in Figure 6 and Figure 7, respectively. Figure 8 illustrates a comparison of cell types between non-Hodgkin's lymphoma TILs and melanoma TILs. An increased trend in the number of CD4* T cells in cells is shown in lymphoma TILs compared to me 1 anaine TILs. Figure 9 illustrates Bioluminescent Redirected Lysis Assay (BRLA) results. The minimal cytolytic activity of TIL measured by BRLA as LUso / lO* a. 4 hrs ranged from <1-6 LU50 and at 24hrs, 1-39 LUse in lymphoma TIL compared to melanoma TIL (11-75 Lülo, 4hrs). Figure 10 illustrates interferon-γ (IFN-γ) enzyme-linked immunosorbent assay results for lymphoma TILs versus melanoma TILs. Comparable results are shown. Results from the ELIspot assay for lymphoma TILs are shown in Figure 1.1 and compared with results from the same assay for melanoma TILs in Figure 12. In the ELIspot assay, a wide range of IFN-γ production by TILs from lymphoma was observed after stimulation with phorbol 12-myristate IS-acetate / ionomycin, anti-CD3 antibody, or CD3 / CD28 / 4-1BB beads, and lFN-γ produced by some lymphoma TILs under these conditions was comparable with the IFN-γ produced by melanoma TILs. and in several cases, IFN-γ production in lymphoma TILs was much higher. Figure 13 illustrates the results of a NANOSTRING NCOUNTER analysis (Nanostring Technologi.es, Inc., Seattle, WA), showing that TILs from lymphoma express higher levels of RORC IL17A (TH17 phenotype) and GAT A3 (Th2 phenotype) compared with melanoma TILs. This finding is consistent with the observation that lymphoma-reactive T cells are primarily ΤΉ2 and TH17. Overall, the results provide evidence that TIL cell therapy can be used to treat patients with lymphoma. Example 2 - Renotypic and Functional Characterization of Marrow Infiltrating Lymphocytes (MIL) Growing from Bone Marrow of Patients with .AML.....and Peripheral Blood Lymphocytes (PBL) Growing from Peripheral Blood of Patients with AML Bone marrow samples, and as available a related blood sample, were obtained from patients with acute myeloid leukemia (AML), which includes patients pre-treated with at least three rounds of a regimen comprising ibrutinib (1 - [(3R)-3-[4-amino-3-(4-phenoxyphenyl)-TH-pyrazolo[3(4-d]pyrimidin-l--yl]--1-piperidinyl]-2-p.ropen- l-one), accompanied by information about the patient's age, gender, stage, tumor type, cancer site, treatment history, a de-identified pathology report, and any molecular tests performed (e.g. , MSI expression, and Raf / Ras expression).The MILs: and PBLs were expanded using one of MIL Method 1, MIL Method 2, or MIL Method C 3, or PBL Method 1, PBL Method 2, or PBL Method 3, and the MILs and PBLs were phenotypically and functionally characterized. Figures 36Ά and 36B illustrate the expansion folds for MILs and PBLs. Figure 36A shows the fold expansion for 3 patients (MILI, MIL2, MIL3) and Figure 3 6B shows the fold expansion for the paired PBLs for patients 2 and 3 (PBL2, PBL3). MIL 1.1 was expanded using the MIL Method 1, the MILI. 2 was expanded using MIL Method 2, and MIL 1.3 was expanded using MIL Method 3, and PBLs were expanded using PBL Method 3. MILI expansion folds show 25 (MIL1.1), 50 (MILI.2 ) , and 75 (MILI. 3) times the increment for each sample within MILI. This preliminarily demonstrates that MIL Method 3 may be a preferred expansion method. The fold expansion data for MIL2 and M.IL3 appear poor, possibly due to low starting cell numbers. For comparison, the starting cell numbers for MILI patient sample 3 (MILI.3) was 138,000 cells, while the starting cell numbers for MIL2 and MIL 3 were 62,000 and 28,000, respectively. The PBL fold expansion shown in Figure 36B for MIL2 and MIL3 was approximately 10-fold and 40-fold, respectively, with similar starting cell numbers (338,000 for PBL2 and 336,000 for PBL3). Figures 3.7A and 37B illustrate the number of IFN-y producing cells for MILs (Figure 37A) and paired PBLs (Figure 37B). MILLI. 3, MIL2, and MIL3 show significant increases in IFN-γ secretion, indicating that MIL Method 3 is a preferred expansion method. Data for PBLs are inconclusive. Figures 38A--38F show subsets of TCRocp+ CD4+, and CD8+ for MILs and PBLs. Figures 3 8A and 38D show TCRab+ subsets for MTLs (Figure 38A) expanded using the 3 Methods (MILL 1, MIL 1.2, MIL 1.3) and for PBLs (Figure 38D) expanded using the PBL .Method 3. The data show that the TCRaPi subseries are at most 100% for all MILs and PBLs, indicating that the expansion process was successful in expanding almost all L-cells. Figures 38B and 38E show CD4 subsets that are decreased by MIL expanded by MIL Method 3 (which correlates with the increase in CD8 subsets in Figure 38C). The PBL data in Figures 38E and 38F appear consistent with the MILI data. 3. Figures 39A-39D and 4A-40D show data for CD4 subsets in MIL (Figures 39A-39D) and PBL (Figures 40A-40D). Figures 3 9A and 4 0A show data for (CCR7+ / CD45RA4) without pretreatment; Figures 39B and 4.0® show data for central memory (CM) T cells (CCR7+ / CD45RA-); Figures 3 9C and 4 0C show data for effector memory (EM) T cells (CCR7- / CD45RA-); and Figures 39D and 40D show data for terminally differentiated effector memory cells (TEMRA) (CCR7- / CD45RA+). All samples expanded using MIL Method 3 (MILI. 3.) and PBL Method 3 (PBL2 and PBL3) are consistent with the CD4 subsets in the comparator, melanoma TIL. Figures 41A-41D and 42A-42D show data for CD8 subsets in MIL (Figures 41A-41.D) and PBL (Figures 42A-42D). Figures 41A and 42A show data for (CCR+ / CD45Ra+) without pretreatment; Figures 41B and 42B show data for central memory (CM) T cells (CCR7+ / CD45RA-); Figures 41C and 42C show data for effector memory (EM) T cells (CCR7- / CD4SRA-); and Figures 4 ID and 42D show data for terminally differentiated effector memory cells (TEMRA) (CCR7- / CD45RA+). Samples expanded using the MIL Method 3 (MILI.3) are consistent with the CD4 subsets in the comparator, melanoma TIL. The data for PBL2 and PBL3- were used as a control. Figures 43A and 43B show data for CD4CD27 and CD8CD27 subsets for MILs (Figure 4.3A) and PBLs (Figure 43B). Figures 44A and 44B show data for CD4CD28 and CD8CD28 subsets for MILs (Figure 44A) and PBLs (Figure 44B). Data for PBLs are shown for day 0 and day 14 of the expansion process for each sample, compared to melanoma TIL. Data, for MILs are shown at day 0 and day 14 for MILI,3 only, compared to melanoma TIL. The CD'28 subsets in MIL and PBL are similar to melanoma TIL. Figures 45A and 4-5B depict a comparison of PD1+ cells within each of the CD4 and CD8 subsets for MILs (Figure 45A) and PBLs (Figure 45B). Figures 46A and 4.6B depict a comparison of LAG3 + cells within each of the CD4 and CD8 subsets for MILs (Figure 46A) and PBLs (Figure 46B). The data for both PD1+ and LAG.3+ show a substantial decrease in the MILI.3 sample during the. day of .0 measurement, while MILL 1 and MILI, 2 seem to trend towards an increase for both PD1 and LAG3 during the. day 0. PBL data was used as a control. Experiments in this Example demonstrate that MILs expanded with MIL Method 3 had higher fold expansion, were highly functional, had a higher proportion of CD8 subsets, and had fewer subsets of CD8 subsets. LAG3 + and PD1 + T cells. The data also shows that the memory substrings are similar to the TIL of I 1 axiom. The data also show that cryopreserved samples appear to have higher expansion times compared to fresh samples. Much of the data for the PSL samples appears to be inconclusive, probably based on the small sample size. Example 3 - Methods for Expanding TILs and Treating Cancers with Expanded TILs Bone marrow is obtained using needle aspiration. The bone marrow sample is aspirated into syringes containing heparin and stored overnight at room temperature. After storage, the contents of the syringes are combined together in a sterile container and tested for quality. Bone marrow is enriched for mononuclear cells (MKTCs) using lymphocyte separation medium (LSM) and centrifugation with a COPE Spectra. Cells on the gradient are harvested to 1st red blood cells and washed using HBSS. The MNCs are cryopreserved using a heta-starch-based cryoprotectant supplemented with 2% HSA and 5% DMSO, reserving some of the MNCs for quality control.The QC vial is thawed to determine the CD3+ and CD387138* cell content of the MNC product. The bone marrow is aspirated and fractionated on a density gradient of lymphocyte separation medium and the cells are harvested near the level of the red cell pellet. This fractionation method substantially removes red blood cells and neutrophils, providing nearly whole bone marrow. The resulting fractionated material is T cells and tumor cells. The bone marrow is Ficolled, and the TILs are expanded using methods known in the art and any method described herein. For example, an exemplary method for expanding TILs is depicted in Figure 14. An exemplary method for expanding TILs and treating a cancer patient with expanded TILs is shown in Figure 15. Example 4 - Phenotypic and Functional Characterization of Growth of Tumor Infiltrating Lymphocytes (TIL) from Non-Hodgkin Lymphoma Tumors The goals of the experiments described in this example include determining whether TILs with therapeutic potential can be isolated and cultured from NHL tumors and comparing characteristics of TILs derived from NHL with melanoma-derived TIL. Materials and methods for removal and expansion of TILs in a patient are as described herein. Patient TILs were removed from a tumor suppressor microenvironment by surgical resection of a lesion, in this case, lymphatic tissue, TILs were expanded using the expansion process described herein to provide 109 to 1011 TILs. NHL-derived TILs (1 mantle cell lymphoma (MCL), 3 follicular lymphoma (FL), 3 diffuse large B-cell lymphoma (DLBCL)) were analyzed for differentiation markers against melanoma-derived TILs using flow cytometry. TILs were analyzed for anti-CD56, anti-TCRab, anti-CD3, anti-CD4, anti-CD8, anti-CD27, and anti-CD2S antibodies. These antibodies were used as Differentiation Panel 1 (DF1). Anti-CD3, anti.-CD4, anti~CD9, anti-CD38, and anti-HLA-DR, anti-CCR7, and anti-CD'45RA antibodies were used as Differentiation Panel 2 (DF2). DF2 to identify the following T cell subsets: naïve (CCR* / CD45Ra+); central memory (CM) T cells (CCR7 + / CD45.RA-); effector memory (EM) T cells (CCR7- / CD45RA-); and terminally differentiated effector memory cells (TEMRA) (CCR7- / CD45RA+). Figures 16A-16D show CD4 and CD8 T cells in different cell subpopulations in different cancer types. Melanoma, mantle cell cancer types were tested. diffuse large B-cell lymphoma and follicular lymphoma. Figures 16A-16D generally demonstrate a tendency for lymphoma TILs to be more highly proliferative and thus have elevated anti-tumor activity - compared to melanoma TILs. Similarly, Figure 17B shows that lymphoma T cells expressing CD4 / CD8 have superior proliferative capacity than melanoma T cells expressing CD4 / CD28. Gamma interferon (IFNγ) production by TILs was measured by stimulating TILs with mAb-coated DynaBeads™ (CD3, CD28, and CD1.37), then using ELlspot™ (Immunospot CTL) and enumerated using 'Immunospot™ input analyzer S6f and also by ELISA using the ELISA DuoSet™ kit (R&D system following manufacturer's instructions). Figures 18A and 18B demonstrate that IFNγ production by NHL TILs and melanoma TILs are similar, indicating similar cytotoxicity functionality between the two types of TILs. The Utic potential of TILs was determined using Bioluminescent Redirected Lysis Assay (BRLA-j). Translucent P815 cells with lentiviral vector encoding eGFP and firefly luciferase were used as target cells. TILs and target cells were co-cultured for 4 hours / 24 hours. hours in the presence of 0KT3, Luciferin was then added and cells were incubated for 5 minutes. Bioluminescence was measured using a luminometer. Percent survival and percent cytotoxicity were calculated as follows: % Survival - (minimum experimental survival) / (maximum signal-minimum signal) x 100% cytotoxicity = 100 - (% survival). The Utic potential of TILs was expressed as a lib unit, LU&o, which represents 50 percent of target cell cytotoxicity induced by effector cells, TILs were tested for their tumor-killing ability in both autologous and allogeneic tumors. TILs were mixed with autologous lymphoma cells or allogeneic melanoma cell lines (.526 melanoma cell line) to different effector cells to target cell ratios (E:T ratio) -either 10:1, 20 :1, 50:1, or 100:1. Tumor cells were labeled with CellTrace Violet dye (ThermoFisher) prior to cutting. After 24 hours, cells were stained with 7-AAD to determine cell death. The proportion of tumor cells killed by TILs was represented as 7-AAD positive tumor cells that were collected in CellTrace Violet stain against CD19 for lymphoma cells and CellTrace Violet stain against MCSP for melanoma cells. Figures 19Ά and 19B show that .NHL TIL and melanoma TIL have similar cytotoxic functionality against both allogeneic and autologous tumors at 4 hours (Figure ISA) and 24 hours (Figure 19B). The analysis of the. Gene expression was also performed on the TILs using the Immunology V2 panel. 'Human nCounter GX (NanoString., Seattle). lOOng of total RNA were assayed per manufacturer's instructions. The data was normalized by scaling with geometric mean of the construct control gene probes for each sample. Data was mapped against and matched to melanoma gene expression. Figure 21 demonstrates the results of gene expression analysis. The heat map shows the fold change in gene expression on melanoma TILs. The expression of IL17A and RORC from lymphoma-derived TILs. it has superior expression compared to melanoma-derived TILs. Overall, the results of this experiment demonstrate that the functional characteristics of lymphoma-derived TILs are similar to melanoma-derived TILs, indicating that the use of lymphoma-derived TILs may be successful in treating lymphoma cancers. Example 5 - Phenotypic and Functional Characterization of Growth of Peripheral Blood Lymphocytes_(PBLs) from Peripheral Blood of Patients........with____Chronic Lymphocytic Leukemia__(CLL) PBMCs were collected from patients with CLL pre- and post-treatment with three rounds of ibrutinib. T cells were expanded using three different Methods, PBL Method 1, PBL Method 2, and PBL Method 3, as described in Figures 24A-24C and elsewhere herein. Certain samples were derived from fresh PBMCs and certain samples were derived from cryopreserved PBMCs. Once the cells were expanded and harvested, they were phenotyped and functionally characterized using the methods described in Example 4, above, and elsewhere herein. The goals of this Example were to determine an optimal expansion process for PBLs and to determine if PBLs expanded from ibrutinib-treated samples are more potent than PBLs expanded from untreated samples. The PBL expansion folds are shown in the Figure. 26. Results are shown for PBLs expanded using .PBL Method 1, PBL Method 2, and PBL Method 3. Untreated PBLs (PreRx PBL) show a mean 179-fold expansion and ibrutinib-treated PBLs (PostRx PBL ) show a mean 306-fold expansion. PBLs derived from fresh PBMC (PBL) show only an average of 82-fold expansion. As between PBLs and PostRx PBLs, p=0.006. Like between PBLs and PreRx PBLs, p=0.3, and like between PreRx PBLs and PostRx PBLs, p=0.1. In general, an increase in mean fold expansion is observed for all PostRx PBL groups over all groups in both PBLs and PreRx PBLs. Figure 27 demonstrates Interferon-gamma (IFN~v) producing cells in PBL, PreRx PBL, and PostRx PBL. For PBL, the mean number of IFN-γ-producing cells was approximately 1,864. For PreRx PBL, the mean number of IFN-γ-producing cells was approximately 7,530, and for PostRx PBL, the mean number of IFN-γ-producing cells was approximately 7,530. was approximately 11984. As between PBLs and PostRx PBLs, p-0,Q06. As between PBLs and PreRx PBLs, p=0.006, and as between PreRx PBLs and PostRx PBLs, p^0.01. In general, a significant increase in the mean number of IFN-y producing cells is observed for all PostRx PBL groups over all groups in both PreRx PBLs and PBLs. The -phenotypic characterization. was performed on each of the samples. The. Figure 2-8 depicts the ratio of CD4+ and CD8+ T cell subsets in PBL PreRx and PBL PostRx, and uses melanoma TIL as a comparator. Here, the data shows that the CD4 subsets (shown on the left) were comparable between both PBL PreRex and PBL PostRx, with respect to which method was used to expand the cells. CD4 subsets in PreRx PBLs and PostRx PBLs are shown to be superior to melanoma TILs (p=0.0006 for each, one). The CD'8 subsets (shown on the right) were inferior in both PBL PreRx and PBL PostRX, relative to the process used to expand the cells. CD8 subsets in PreRx PBLs and PostRx PBLs are shown to be lower than melanoma TILs (ρ^Ο,-0006 for each). It is hypothesized that the lower CD8 subsets are only a derivative of the cancer type (ie, in CLL·, CD4 subsets are typically expanded). Figures 29A-29D depict a comparison between CD4 memory subsets of PreRx PBLs and PostRx PBLs, using melanoma TIL as a comparator. Figure 29A shows data for (CCR7+ / CD'45.RA+j: naïve; Figure 29B shows data for central memory (CM) T-cell (CCR7+ / CD45RA-); Figure 29C shows data for for effector memory (EM) T cells (CCR7- / .CD45RA-), and Figure 29D shows data for terminally differentiated memory (TEMRA) cells (CCR7-- / CD4.5RA+). demonstrate that the CD4 memory subsets for PreRx PBLs and PostRx PBLs are comparable to those seen for melanoma TILs. Figures 30A-30D depict a comparison between CD8 memory subset of PreRx PBLs and PostRx PBLs, using melanoma TIL as a comparator. Figure 30A shows data for (CCR7+ / CD45RA+) naïve; Figure 30B shows data for central memory (CM) T cells (CCR7-J- / C.D45RA-·); Figure 3 0C shows data for effector memory T cells (ΈΜ) (CCR7- / CD45RA-); and Figure 30D shows data for terminally differentiated memory cells (TEMRA) (CCR7- / CD45RA+). The Figures 30A--30D demonstrate that the CD8 memory subsets for PreRx PBLs and PostRx PBLs are comparable to those seen for melanoma TILs. Figures 3ΊΑ and 3IB depict a comparison of CD27 subsets of CD4 cells (FIG. 31A) and CD8 cells (FIG. 3IB'), using melanoma TIL as a comparator. CD4CD27 cell subsets were significantly superior in both PBL PreRx (p-0.03) and PBL PostRx (p=0.02) compared to melanoma TIL. The CD8CD27 cell subsets were significantly superior in both PBL PreRx (p=Q.002) and PBL PostRx (p^0.001) compared to melanoma TIL. Figures 32A and 32B' depict a comparison of CD28 subsets of CD4 cells (FIG. 32A) and CD8 cells (FIG. 32B), using melanoma TIL as a comparator. As CD4CD28 cell subsets and CD8CD2.8 cell subsets are shown to be comparable for both the PBL. PreRx as PBL PostRx compared with melanoma TIL. Figures 33A. and 33B depict a comparison of LAG.3 + subsets within the CD4 + (FIG. 33A) and CD8 + (FIG. 33B) populations for PreRx PBLs and PostRx PBLs. The data show a significant mean decrease in LAG3-+ subsets in both CD4+ (p-0.06) and CD8+ (p-G. 01.) populations in PostRx PBLs. Figures 34A and 34B represent one. comparison of PD1+ subsets within the CD4+ (FIG. 34A) and CD8+ (FIG. 34B) populations for PreRx PBLs and PostRx PBLs. The data show a mean decrease in PD14-subsets in both CD4+ and CD8+ populations in the PostRx PBLs, but the decrease was not significant. Figures 35A and 35B show the results of the cytolytic activity of PreRx PBLs (Figure 3.5-A) and PostRx PBLs (Figure 35Β), measured using a Bioluminescent Redirected Lysis Assay (BRLA). The assay was performed using the CellTrace™ Violet Cell Proliferation Kit (Invitrogen) as follows: Effector cells, which are the PBLs, were labeled with carboxyfluorescein succinimidyl ester (CFSS). Target cells (autologous CD19+ tumor cells) were incubated with Mitamycin C, and then labeled with CellTrace™ Violet (CTV) according to the CellTrace Violet Cell Proliferation Kit instructions. Effector and target cells were incubated for 24 hours at ratios of 2:1, 5:1, and 20::1 (cells were added, cells were stained with Annexin V-PI, and then analyzed). to determine GTV / Annexin-V PI+ cells (which gives the number of dead cells) PostRx PBLs appear to be more potent because fewer cells are required to kill 50% of target tumor cells (i.e., LÜsc is lower for PostRx PBLs than for PreRx PBLs). The experiments performed in this example demonstrate the following results. PBLs .expanded from fresh FLC PBMCs show lower fold expansion and significantly less IFN-γ production compared to PBLs expanded from cryopreserved PBMCs (PBLs PreRx and PBLs PostRx); PostRx PBLs consistently showed higher fold expansion and significant increase in ΙΕΝ-γ production compared to PreRx PBLs; and both PreRx PBLs and PostRx PBLs showed lytic activity against autologous tumor cells (CD15+), although PostRx PBLs have a lower LU50 than PreRx PBLs. The examples set forth above are provided to give those of ordinary skill in the art a complete description and disclosure of how to make and use the embodiments of the compositions, systems, and methods of the invention, and are not intended to limit the scope of the foregoing. that the inventors regard as their invention. Modifications of the modes for carrying out the invention described above that are obvious to persons skilled in the art are intended to be within the scope of the following claims. All patents and publications mentioned in the description are indicative of the skill levels of those skilled in the art. to which the invention belongs. All headings and section designations are used for clarity and reference purposes only and are not to be considered limiting in any way. For example, those of skill in the art will appreciate the utility of combining various aspects of different headings and sections as appropriate consistent with the spirit and scope of the invention described herein. All references cited herein are hereby incorporated by reference herein in their entireties and for all purposes to the same extent as if each individual publication or patent or patent application is specifically and individually indicated to be incorporated by reference. in its entirety for all purposes. Many modifications and variations may be made to this application without departing from its spirit and scope, as will be apparent to those skilled in the art. The specific embodiments and examples described herein are offered by way of example only, and the application is to be limited by the terms of the appended claims, together with the full scope of equivalents to which the claims are entitled. It is stated that in relation to this date, the best method known by the applicant to carry out the aforementioned invention is the one that is clear from the present description of the invention.

Claims

1. A method for treating cancer in a patient with a tumor-infiltrating lymphocyte (TIL) population, characterized in that it comprises the steps of: (a) optionally pre-treating a patient with a regimen comprising ibrutinib; (b) obtaining a liquid tumor; (c) optionally fragmenting or dissociating the tumor to obtain tumor fragments and contacting the tumor fragments with a first cell culture medium; (d) performing an initial expansion of the first TIL population in the first cell culture medium to obtain a second TIL population, wherein the second TIL population is .at least: 5-fold greater in number than the first TILs population, wherein the first cell culture medium comprises IL-2, and wherein the initial expansion is carried out over a period of 21 days or less; (e) carrying out a second expansion of the second TILs population in a second cell culture medium to obtain a third TILs population, wherein the third TILs population is at least 10-fold greater in number than the second TILs population after 7 days from the start of the second expansion; wherein the second cell culture medium comprises IL-2, OKT-3 (anti-CD3 antibody), and irradiated allogenic peripheral blood mononuclear cells (PBMCs), and wherein the second expansion is carried out over a period of 14 days or less; (f) collect the third population of TILs, and (g) administer a therapeutically effective portion of the third population of TILs to a patient with cancer; wherein the cancer is a hematologic neoplasm.

2. The method according to claim 1, characterized in that it further comprises the addition of an ITK inhibitor, wherein the ITK inhibitor is optionally an ITK inhibitor that is covalently bound to ITK.

3. The method according to claim 1, characterized in that an ITK inhibitor is added to the first cell culture medium during step (d), to the second cell culture medium during step (e), or to both the first cell culture medium during step (d) and the second cell culture medium during step (e).

4. The method according to claim 1, characterized in that the ITK inhibitor is selected from the group consisting of aminothiazole-based ITK inhibitors, benzimidazole-based ITK inhibitors, aminopyrimidine-based ITK inhibitors, 3-aminopyrido-2-one-based ITK inhibitors, indole-indazole-based ITK inhibitors, pyrazolyl-indole-based inhibitors, thienopyrazole-based ITK inhibitors, and ITK inhibitors targeting cysteine-442 in the ATP cavity.

5. The method according to claim 4, characterized in that: the ITK inhibitor is selected from the group consisting of ibrutinib, dasatinib, bosutinib, nilotinib, erlotinib BMS5Q.9744, -CTAQ56, GSK2250.665A, PF06465469 ( (R) -3- (!- (1 -acryloylpiperidin-3-yl) -4-amino-1H-pyrazolo [3·,4-d] pyr.imidin-3-yl) -N- (3-methyl'l~4- (1-methylethyl))benzamide), and combinations thereof.

6. The method according to claim 5, characterized in that the ITK inhibitor is ibrutinib.

7. The method according to claim 2, characterized in that the ITK inhibitor is added at a concentration from approximately 0.1 nM to approximately 5 μM.

8. The method according to claim 1, characterized in that the initial expansion is carried out over a period of between 3 days and 11 days.

9. The method according to claim 1, characterized in that the second expansion is carried out during a period of between 3 days and 11 days.

10. The method according to claim 1, characterized in that IL-2 is present at an initial concentration of between 1000 IU / ml and 6000 IU / ml in the first cell culture medium.

11. The method according to claim 1, characterized in that IL-2 is present at an initial concentration of between 1000 IU / mL and 6000 IU / mL and the OKT-3 antibody is present at an initial concentration of approximately 30 ng / mL in the second cell culture medium.

12. The method according to claim 1, characterized in that the initial expansion is carried out using a gas-permeable container.

13. The method according to claim 1, characterized in that the second expansion is carried out using a gas-permeable container.

14. The method according to claim 1, characterized in that the first cell culture medium further comprises a cytokine selected from the group consisting of IL-4, IL-7, IL-15, IL-21, and combinations thereof.

15. The method according to claim 1, characterized in that the second cell culture medium further comprises a cytokine selected from the group consisting of IL-4, IL-7, IL-15, IL-21, and combinations thereof.

16. The method according to claim 1, characterized in that it further comprises the step of treating the patient with a non-myeloablative lymphatic depletion regimen prior to administering the third TILs population to the patient.

17. The method according to claim 16, characterized in that the non-myeloablative lympho-depletion regimen comprises the steps of administering cyclophosphamide at a dose of 60 mg / m2 / day for two days followed by administering fludarabine at a dose of 25 mg / m2 / day for five days.

18. The method according to claim 1, characterized in that it further comprises the step of treating the patient with a high-dose IL-2 regimen starting on the day after the administration of the third TIL population to the patient.

19. The method according to claim 18, characterized in that the high-dose IL-2 regimen comprises 600,000 or 720,000 IU / kg of aldesleucine, or a biosimilar or variant thereof, administered as an intravenous infusion, 15-minute bolus every eight hours until tolerance.

20. The method according to claim 1, characterized in that the cancer is selected from the group consisting of acute myeloid leukemia (AML), mantle cell lymphoma (MCL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), activated B-cell DLBCL (ABC), germinal central B-cell DLBCL (GCB), chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, relapsed and / or refractory Hodgkin lymphoma, acute B-cell lymphoblastic leukemia (B-ALL), mature B-ALL, Burkitt lymphoma, Waldenstrom macroglobulinemia (WM), multiple myeloma, myelodysplastic syndromes, myelofibrosis. chronic myelocytic leukemia, follicular center lymphoma, indolent NHL, human immunodeficiency virus (HIV)-associated B-cell lymphoma, and Epstein-Barr virus (EBV)-associated B-cell lymphoma.

21. The method according to claim 1, characterized in that the patient population is a patient population pretreated with ibrutinib.

22. A process for preparing a tumor-infiltrating lymphocyte (TIL) population from a tumor, characterized in that it comprises the steps of: (a) fragmenting the tumor; (b) performing an initial expansion of the first TIL population in a first cell culture medium to obtain a second TIL population, wherein the second TIL population is at least 0.5 times larger.(a) performing a second expansion of the second TILs population in a second cell culture medium to obtain a third TILs population, wherein the third TILs population is at least 50-fold greater in number than the second TILs population after 7 days from the start of the second expansion; wherein the second cell culture medium comprises IL-2, OKT-3 (anti-CD3 antibody), irradiated allogeneic peripheral blood mononuclear cells (PBMCs); and wherein the second expansion is performed for a period of 14 days or less; and (d) collecting the third TILs population, wherein the tumor is a liquid tumor, and wherein the cancer is a hematologic neoplasm.

23. The process according to claim 22, characterized in that the first TILs population is obtained from a tumor or portion thereof.

24. The process according to claim 23, characterized in that the tumor or portion thereof has been removed from a patient.

25. The process according to claim 22, characterized in that the initial expansion is carried out during a period of 14 days or less.

26. The process according to claim 22, characterized in that the initial expansion is carried out during a period of 11 days or less.

27. The process according to claim 22, characterized in that the second expansion is carried out during a period of 11 days or less.

28. Use of a liquid tumor in the manufacture of a population of TILs for the treatment of a hematologic neoplasm.

29. A method for expanding TILs obtained from bone marrow or peripheral blood, characterized in that it comprises: (a) identifying a first population of TILs from a sample of bone marrow or peripheral blood; (b) performing an initial expansion of the first population of TILs in a first cell culture medium to obtain a second population of TILs, wherein the second population of TILs is at least 5 times greater in number than the first population of TILs, wherein the first cell culture medium comprises IL-2, and wherein the initial expansion is carried out over a period of 21 days or less;(c) performing a second expansion of the second TILs population in a second cell culture medium to obtain a third TILs population, wherein the third TILs population is at least 50-fold greater in number than the second TILs population after 7 days from the start of the second expansion; wherein the second cell culture medium comprises IL-2, OKT-3 (anti-CD3 antibody), and irradiated allogeneic peripheral blood mononuclear cells (PBMCs), and wherein the second expansion is performed over a period of 14 days or less; (d) collecting the third TILs population; and (e) providing such third TILs population to such patient.

30. The method according to claim 29, characterized in that the initial expansion is carried out during a period of 11 days or less.

31. The method according to claim 29, characterized in that the second expansion is carried out during a period of 11 days or less.

32. The method according to claim 29, characterized in that IL-2 is present at an initial concentration of between 1000 IU / mL and 6000 IU / mL in the first cell culture medium.

33. The method according to claim 29, characterized in that IL-2 is present at an initial concentration of between 1000 IU / mL and 6000 IU / mL and the OKT-3 antibody is present at an initial concentration of approximately 30 ng / mL in the second cell culture medium.

34. The method according to claim 29, characterized in that the initial expansion is performed using a gas-permeable container.

35. The method according to claim 29, characterized in that the second expansion is carried out using a gas-permeable container.

36. The method according to claim 29, characterized in that the first cell culture medium further comprises a cytokine selected from the group consisting of IL-4, IL-7, IL-15, IL-21, and combinations thereof.

37. The method according to claim 29, characterized in that the second cell culture medium further comprises a cytokine selected from the group consisting of IL-4, IL-7, IL-15, IL-21, and combinations thereof.

38. A method for expanding peripheral blood lymphocytes (PBLs) from peripheral blood, characterized in that it comprises: a. obtaining a sample of peripheral blood mononuclear cells (PBMCs) from peripheral blood, wherein such sample is optionally cryopreserved; b. isolating PBLs from such sample by selecting and removing CD19+ B cells; c. optionally co-culturing such PBLs with such CD19+ B cells; d. stimulating such PBLs in a first cell culture medium with IL-2 and anti-CD3 / anti-CD28 antibodies for a period of approximately 2 to approximately 6 days in a gas-permeable container; e. culturing the PBLs from step (d) for a period of approximately 2 to approximately 6 days with IL-2 and anti-CD3 / anti-CD28 antibodies; f. isolating the antibody-bound PBLs from the culture in step (e); g. remove the antibodies from the PBLs isolated in step (e); and h. collect the PBLs.

39. The method according to claim 1, characterized in that the first cell culture medium is selected from the group consisting of CM-2, CM-4, and AIM-V.

40. The method according to claim 38, characterized in that after step (d), additional IL-2 is added and the first cell culture medium is exchanged with a second cell culture medium.

41. The method according to claim 38, characterized in that after step (e), additional IL-2 is added and the second culture medium is exchanged with a third cell culture medium.

42. The method according to claim 40, characterized in that the second cell culture medium is selected from the group consisting of CM-2, CM-4, and AIM-V.

43. The method according to claim 41, characterized in that the third cell culture medium is selected from the group consisting of CM-2, CM-4, and AIM-V.

44. The method according to claim 40, characterized in that the first cell culture medium and the second cell culture medium are different.

45. The method according to claim 40, characterized in that the first cell culture medium and the second cell culture medium are the same.

46. ​​The method according to claim 38, characterized in that the ratio of B-cells to PBLs in step (c) is from approximately 0.1:1 to approximately 10:1 (B-cells:PBLs).

47. The method according to claim 38, characterized in that the ratio of B cells to PBLs in step (c) is selected from the group consisting of 0.1-1, 1:1, and 10:1 (B cells:PBLs).

48. The method according to claim 38, characterized in that there are at least from approximately 1xlO5 to approximately 1OxlO5 PBLs in the gas-permeable container at the beginning of step (d).

49. The method according to claim 38, characterized in that there are at least from approximately 2.5xlO5 to 10xl0s PBLs in the gas-permeable container at the beginning of step (d).

50. The method according to claim 38, characterized in that: there are at least .SxlO5 PBLs in the gas-permeable container at the beginning of step (d).

51. The method according to claim 38, characterized in that IL-2 is present at a concentration of between 1000 IU / ml and 6000 IL / ml in steps (c) and (d).

52. The method according to claim 51, characterized in that TL~2 is present at a concentration of approximately 3000 IU / ml.

53. The method according to claim 38, characterized in that the antibodies, anti-CD3 / anti-CD28, are coated onto beads and the PBL:bead ratio is approximately 1:1 in each of steps (c) and (d).

54. The method according to claim 38, characterized in that it further comprises the addition of an ITK inhibitor.

55. The method according to claim 54, characterized in that an ITK inhibitor is added during at least one of step (c), step (d), and step (e).

56. The method according to claim 54, characterized in that the ITK inhibitor is selected from the group consisting of aminothiazole-based ITK inhibitors, benzimidazole-based ITK inhibitors, aminopyrimidine-based ITK inhibitors, 3-aminopyrido-2-one-based ITK inhibitors, indolindazole-based ITK inhibitors, pyrazolyl-indole-based inhibitors, thienopyrazole inhibitors, and ITK inhibitors targeting cysteine-442 in the ATP cavity, 57. The method according to claim 56, characterized in that the ITK inhibitor is selected from the group consisting of ibrutinib, dasatinib, bosutinib, nilotinib, erlotinib BMS509744, CTA056, GSK22S0665A, PF06465469 ( (R) -3-(1- (l-acryloylpiperidin-3-yl) -4-amino-lH-pyrazol-l [3,4-d]pyrimidin-3-yl} -N- (3-methyl-4- (1-methyleth-yl)berizamide) , and combinations thereof.

58. The method according to claim 57, characterized in that the ITK inhibitor is ibrutinib, 59. The method according to claim 38, characterized in that the method is performed in a closed, sterile system, 60. A method for expanding peripheral blood lymphocytes (PBLs) from peripheral blood, characterized in that it comprises: a. obtaining a sample of PBMCs from peripheral blood of a patient, wherein such sample is optionally cryopreserved and the patient is optionally pretreated with an ITK inhibitor; b. isolating PBLs from such sample by selecting and removing CD19+ B cells and optionally pretreating such PBLs with an ITK inhibitor at a concentration of between 0.1 nM and 20 nM; c. co-culturing such PBLs with such CD19+ B cells for a period of between 2 and 5 days; d. Add from approximately 2.5x105 to approximately 5x10·' cells to a gas permeable container in a prime cell culture medium and stimulate such PBLs with 3000 IU / ml of IL-2' and anti-CD3 / anti-CD28 antibodies immobilized on beads, and optionally an ITK inhibitor at a concentration between 0.1 nM and 200 nM, for a period of between 3 and 6 days;e.exchange the first cell culture medium with a second cell culture medium and add additional IL-2 at a concentration of approximately 300.0 IU / ml and optionally an ITK inhibitor at a concentration between 0.1 nM and 200 nM; f. culture the PBLs from step (e) for an additional period of between 3 and 6 days with IL-2 and anti-CD3 / anti-CD28 antibodies immobilized on beads and optionally an ITK inhibitor at a concentration between 0.1 nM and 200 nM; g. exchange the second cell culture medium with a third cell culture medium and add additional IL-2 at a concentration of 3000 IU / mL, and optionally an ITK inhibitor at a concentration between 0.1 nM and 200 nM, and culture the cells for an additional period of between 2 and 5 days; h. isolate the antibody-bound PBLs from the culture in step (g);i. remove the antibodies from the isolated PBLs in step (h); andj.collect the PBLs, wherein the ITK inhibitor is an ITK inhibitor that binds oovalently to ITK.

61. A method for treating a hematologic neoplasm, characterized in that it comprises: a. obtaining a sample of PBMCs from peripheral blood of a patient suffering from a hematologic neoplasm; b. isolating PBLs from such a sample by selecting and removing CD19+ B cells; c. optionally co-culturing such PBLs with such CD19+ B cells; d. stimulating such PBLs in a first cell culture medium with IL-2 and anti-CD3 / anti-CD28 antibodies for a period of approximately 2 to approximately 6 days in a gas-permeable container; e. culturing the PBLs from step (d.) for a period of approximately 2 to approximately 6 days with IL-2 and anti-CD3 / anti-CD28 antibodies; f. isolating antibody-bound PBLs from the culture in step (e); g. removing the antibodies from the PBLs isolated in step (f); and h. collecting the PBLs; i. administer the PBLs to the patient in a therapeutically effective amount to treat such hematologic neoplasm.

62. The method according to claim 61, characterized in that the patient is pre-treated with an ITK inhibitor prior to obtaining a PBMC sample.

63. The method according to claim 62, characterized in that the ITK inhibitor is selected from the group consisting of aiftinothiazole-based ITK inhibitors, benzimidazole-based ITK inhibitors, aminopyrimidine-based ITK inhibitors, 3-aminopyrido-2-one-based ITK inhibitors, indolindazole-based ITK inhibitors, pyrazolindol-based inhibitors, thienopyrazole inhibitors, and ITK inhibitors targeting cysteine-442 in the ATP cavity.

64. The method according to claim 62, characterized in that the ITK inhibitor is selected from the group consisting of ibrutinib, dasatinib, bosutinib, nilotinib, erlotinib RMS5Q9744, CTA.056, GSK2250665A, PF06465469 ( (R) -3- (1- (1-acryloylpiperidin-3 -yl) -4-amino-1H-pyrazolo [3,4 -d] pyrimidin-3-yl) -N- (3-met i 1-4 - (1-methylethyl) .)'benzamide), and combinations thereof.

65. The method according to claim 64, characterized in that the ITK inhibitor is ibrutinib.

66. The method according to claim 62, characterized in that the patient is pre-treated with at least three rounds of an ibrutinib regimen.

67. The method according to claim 61, characterized in that the hematological neoplasm is selected from the group consisting of acute myeloid leukemia (AML), mantle cell lymphoma (MCL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), activated B-cell lymphoma (ABC), DLBCL. Central germ cell B-cell (GCB) lymphoma, chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, relapsed and / or refractory Hodgkin lymphoma, acute B-cell lymphoblastic lymphoma (B-ALL), mature B-ALL, Burkitt lymphoma, Waldenstrom macroglobulinemia (WM), multiple myeloma, myelodysplastic syndromes, myelofibrosis, chronic myelocytic leukemia, follicular center lymphoma, indolent HNE, human immunodeficiency virus (HIV)-associated B-cell lymphoma, and Epstein-Barr virus (EBV)-associated B-cell lymphoma. 6.8.The method according to claim 61, characterized in that the hematological neoplasm is chronic lymphocytic leukemia (CLLJ).

69. The method according to claim 61, characterized in that the first cell culture medium is selected from the group consisting of CM-2, CM-4, and AIM-V.

70. The method according to claim 61, characterized in that after step (d), additional IL-2 is added and the cell culture medium is exchanged with a second cell culture medium.

71. The method according to claim 70, characterized in that after step (e), additional IL-2 is added and the second cell culture medium is exchanged with a third cell culture medium.

72. The method according to claim 70, characterized in that the second cell culture medium is selected from the group consisting of CM-2, CM-4, and AIM-V.

73. The method according to claim 71, characterized in that the third cell culture medium is selected from the group consisting of CM-2, CM-4, and AIM-V.

74. The method according to claim 70, characterized in that the first cell culture medium and the second cell culture medium are different.

75. The method according to claim 70, characterized in that the first cell culture medium and the second cell culture medium are the same.

76. The method according to claim 61, characterized in that the ratio of B cells to PBLs in step (c) is from approximately 0.1:1 to approximately 1.0:1 (B cells:PBLs).

77. The method according to claim 61, characterized in that the ratio of B cells to PBLs in step (c) is selected from the group consisting of 0.1:1, 1:1, and 10:1 (B cells:PBLs).

78. The method according to claim 61, characterized in that there are at least from approximately 1x10® to approximately 10x103 PBLs in the gas-permeable container at the beginning of step (d).

79. The method according to claim 61, characterized in that there are at least from approximately 2.5X105 to 10x105 PBLs in the gas-permeable container at the beginning of step (d).

80. The method according to claim 61, characterized in that there are at least 5 x 1.0s PBLs in the gas-permeable container at the beginning of step (d).

81. The method according to claim 61, characterized in that IL-2 is present at a concentration of between 1000 IU / ml and 6000 IL / ml in steps (d) and (e).

82. The method according to claim 81, characterized in that IL-2 is present at a concentration of approximately 3000 IU / ml, 83. The method according to claim 61, characterized in that the anti-CD3 / anti-CD28 antibodies are coated on beads and the PBLs:beads ratio is approximately 1:1 in each of steps (d) and (e).

84. The method according to claim 61, characterized in that the PBLs are administered in an amount from approximately 0.1x10® to approximately 15x10' PBLs.

85. A method for expanding bone marrow infiltrating lymphocytes (MILs) from bone marrow, characterized in that it comprises: a. obtaining a sample of peripheral blood neutrophils (PBMCs) from bone marrow, wherein such sample is optionally cryopreservative; b. sorting a fraction of CD3+, CD33+, CD20+ and CD14+ cells (MIL fraction) and a fraction of non-CD3+, non-CD33+, non-CD20+ and non-CD14+ cells (AML blast cell fraction); c. optionally altering the AML blast cell fraction; d. adding the optionally altered AML blast cell fraction to the MIL cell fraction in a cell number ratio of approximately 0.1:1 to approximately 10:1; e. culturing one or both cell fractions in a gas-permeable container in a first cell culture medium comprising IL-2; f. Stimulate MILs with anti-CD3 / anti-CD28 antibodies to obtain MIL expansion;g.Restimulate the MILs with IL-2 and anti-CDS / anti-CD28 antibodies for an additional period of approximately 2 to approximately 6 days; h. Culture the MILs with additional IL-2 for an additional period of approximately 1 to approximately 3 days; i. Collect such MILs.

86. The method according to claim 85, characterized in that the first cell culture medium is selected from the group consisting of CM-2, CM-4, and AIM-V.

87. The method according to claim 85, characterized in that after step (e) is initiated, additional IL-2 is added and the first cell culture medium is exchanged with a second cell culture medium.

88. The method according to claim 87, characterized in that the second cell culture medium is selected from the group consisting of CM-2, CM-4, and AIM-V.

89. The method according to claim 87, characterized in that the first cell culture medium and the second cell culture medium are different.

90. The method according to claim 87, characterized in that the first cell culture medium and the second cell culture medium are the same.

91. The method according to claim 85, characterized in that there are at least from approximately 2x10'* to approximately .5x105 MILs in the gas-permeable container at the beginning of step (e).

92. The method according to claim 85, characterized in that there are at least from approximately 2.8x10* to 3.4X105 MILs in the gas-permeable container at the beginning of step (e) > 93. The method according to claim 85, characterized in that there are at least Sxlú5 MILs in the gas-permeable container at the beginning of step (e).

94. The method according to claim 85, - characterized in that IL-2 is present at a concentration of between 1000 IU / ml and 6000 IU / ml in step (d).

95. The method according to claim 94, characterized in that IL-2 is present at a concentration of approximately 6000 IU / ml.

96. The method according to claim 85, characterized in that IL-2 is present at a concentration of approximately 3000 IU / ml in step (f).

97. The method according to claim 85, characterized in that the cultivation in step (d) is carried out over a period of approximately 3 days.

98. The method according to claim 85, characterized in that the stimulation in step (e) is performed over a period of approximately 4 days, 99. The method according to claim 85, characterized in that the stimulation in step (f) is carried out over a period of approximately 7 days.

100. The method according to claim 85, characterized in that the additional IL-2 in step (g) is present at a concentration of approximately 3000 IU / ml.

101. The method according to claim 85, characterized in that the anti-CD3 / anti-CD28 antibodies are coated onto beads and the ratio of MILs: beads is approximately 1:1 in each of steps (e) and (f).

102. The method according to claim 85, characterized in that the optionally altered cell fraction is altered using a method selected from the group consisting of sonication, vortices, vibration, and 1 i sis.

103. The method according to claim 85, characterized in that the cell number ratio of the AML blast cell fraction to the MIL fraction is approximately 1:

1.

104. The method according to claim 85, characterized in that it is performed in a closed, sterile system.

105. A method for expanding bone marrow infiltrating lymphocytes (MILs) from bone marrow, characterized in that it comprises: a. obtaining a sample of peripheral blood mononuclear cells (PBMCs) from bone marrow, wherein such sample is optionally cryopreserved; b. sorting a fraction of CD3+, CD33+, CD20+ and CD14+ cells and a fraction of non-CD3+, non-CD33+, non-CD20+ and non-CD14+ cells; c. altering the AML blast cell fraction and adding the altered AML blast cell fraction to the MIL cell fraction in a cell number ratio of approximately 1:1; d. culturing the AML blast cell fraction and the MIL cell fraction in a gas-permeable container in a first cell culture medium comprising IL-2 at a concentration of approximately 6000 IU / ml for a period of approximately 3 days; e. add anti-CD3 antibodies / .anti-.CD28 immobilized on beads to cell culture at a ratio of approximately 1:1 (MILs:beads·) and culture the MILs and antibodies for a period of approximately 1 day; f. exchange the first cell culture medium with a second cell culture medium comprising additional IL-2 at a concentration of approximately 3000 IU / ml; g. culture the antibody beads and MILs for a further period of approximately 3 days; h. restimulate the MILs with IL-2 and anti-CD3 / axiti-CD28 antibodies immobilized on beads for a further period of at least approximately 4 days; i. exchange the second cell culture medium with a third cell culture medium comprising additional IL-2 at a concentration of approximately 3000 IU / ml for a further period of at least approximately 3 days; and j. collect such MILs.

106. A method for treating a hematologic neoplasm, characterized in that it comprises: a. obtaining a sample of peripheral blood mononuclear cells (PBMCs) from bone marrow, wherein such sample is optionally cryopreserved; b. classifying a fraction of CD3+, CD33+, CD20+ and CD14+ cells (MIL· fraction) and a fraction of non-CD3+, non-CD33+, non-CD20+ and non-CD14+ cells (AML blast cell fraction); c. optionally altering the AML· blast cell fraction; d. adding the optionally altered AML· blast cell fraction to the MIL cell fraction in a cell number ratio of approximately 0.1:1 to approximately 10:1; e. culturing one or both cell fractions in a gas-permeable container in a first cell culture medium comprising IL-2; f. Stimulate MILs with anti-CD3 / anti-CD2 antibodies to obtain MIL expansion;g. restimulate MILs with IL-2 and anti-CD antibodies.3 / anti-CD28 for an additional period of from approximately 2 to approximately 6 days; h. culture the MILs with additional IL-2 for an additional period of from approximately 1 to approximately 3 days; i. collect such MILs; and j. administer such MILs to a patient in a therapeutically effective amount to treat the hematologic malignancy.

107. The method according to claim 106, characterized in that the hematological neoplasm is selected from the group consisting of acute myeloid leukemia (AML), mantle cell lymphoma (MC'L), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), activated B-cell DLBCL (ABC), germinal central B-cell DLBCL (GCB), chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, lymphoma. Relapsing and / or refractory Hodgkin's disease, acute lymphoblastic B-cell lymphoma (B-ALL), mature B-ALL, Burkitt lymphoma, Waldenstrom macroglobulinemia (WM), multiple myeloma, myelodysplastic syndromes, myelofibrosis, chronic myelocytic leukemia, follicular center lymphoma, indolent NHL, B-cell lymphoma associated with human immunodeficiency virus (HIV), and B-cell lymphoma associated with Epstein-Barr virus (EBV).108.The method according to claim 107, characterized in that the hematological neoplasm is acute myeloid leukemia (AML).

109. The method according to claim 106, characterized in that the first cell culture medium is selected from the group consisting of CM-2, CM-4, and ADV1-V.

110. The method according to claim 106, characterized in that after step (e) is performed, additional IL-2 is added and the first cell culture medium is exchanged for a second cell culture medium.

111. The method according to claim 110, characterized in that the second cell culture medium is selected from the group consisting of CM-2, CM-4, and AIM-V.

112. The method according to claim 110, characterized in that the first cell culture medium and the second cell culture medium are different. 11.

3. The method according to claim 110, characterized in that the first cell culture medium and the second cell culture medium are the same.

114. The method according to claim 106, characterized in that there are at least from approximately 2x104 to approximately 5x105 MILs in the gas-permeable container at the beginning of step (e).

115. The method according to claim 106, characterized in that there are at least from approximately 2.6x104 to 3.4x105 MILs in the gas-permeable container at the beginning of step (e).

116. The method according to claim 106, characterized in that there are at least 5x105 MILs in the gas-permeable container at the beginning of step (d).

117. The method according to claim 106, characterized in that IL-2 is present at a concentration of between 100 IU / ml and 6000 IU / ml in step (d).

118. The method according to claim 117, characterized in that IL-2 is present at a concentration of approximately 6000 IU / ml.

119. The method according to claim 106, characterized in that IL-2 is present at a concentration of approximately 3000 IU / ml in step (f).

120. The method according to claim 106, characterized in that the cultivation in step (e) is carried out for a period of approximately 3 days.

121. The method according to claim 106, characterized in that 1.a stimulation in step (f) is carried out for a period of approximately 4 days, 122. The method according to claim 106, characterized in that the stimulation in step (g) is carried out for a period of approximately 7 days.

123. The method according to claim 106, characterized in that it comprises a step of IL~2 supplementation performed after step (f).

124. The method according to claim 123, characterized in that the additional IL-2 is present at a concentration of approximately 3000 IU / ml.

125. The method according to claim 106, characterized in that the anti-CD3 / anti-CD28 antibodies are coated onto beads and the bead:MIL ratio is approximately 1:1 in each of steps (f) and (g).

126. The method according to claim 106, characterized in that the MILs are administered in an amount from approximately 4x10a to approximately 2.5x10s MILS.