PHARMACEUTICAL COMBINATIONS COMPRISING AN ANTI-Y75 ANTIBODY AND VENOTOCLAX FOR USE IN THE TREATMENT OF CANCER.

Abstract

The present invention relates to a pharmaceutical combination comprising: (C) an anti-LY75 antibody, or an antigen-binding portion thereof, wherein the antibody or antigen-binding portion thereof comprises: (c) a variable heavy chain region comprising: (iv) a first vhCDR comprising SEQ ID NO: 5; (v) a second vhCDR comprising SEQ ID NO: 6, and (vi) a third vhCDR comprising SEQ ID NO: 7; and (d) a variable light chain region comprising: (iv) a first vlCDR comprising SEQ ID NO: 8; (v) a second vlCDR comprising SEQ ID NO: 9, and (vi) a third vlCDR comprising SEQ ID NO: 10; wherein the anti-LY75 antibody or antigen-binding portion thereof further comprises a covalently bound drug, wherein the drug is DM4 or DM1; and (D) Venetoclax a pharmaceutically acceptable salt thereof, for use in the treatment of diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin lymphoma in patients.

Description

PHARMACEUTICAL COMBINATIONS FIELD OF THE INVENTION The present disclosure relates generally to the fields of immunology and molecular biology. More specifically, provided are pharmaceutical combinations comprising (A) antibodies, or antigen-binding portions thereof, directed against LY75, and (B) Venetoclax; methods for preparing pharmaceutical combinations; and methods for treating diseases, such as cancers mediated by LY75 expression or activity. BACKGROUND OF THE INVENTION Leukemias and lymphomas belong to a broad group of tumors that affect the blood, bone marrow, and lymphatic system; these are known as tumors of the hematopoietic and lymphoid tissues. Lymphoma is a group of tumors of blood cells, which develops from lymphocytes. Signs and symptoms may include enlarged lymph nodes, fever, sweating, unintentional weight loss, itching, and a persistent feeling of tiredness. There are a number of subtypes of lymphomas: the two main categories of lymphomas are Hodgkin lymphomas (HL) and non-Hodgkin lymphomas (NHL). The World Health Organization (WHO) includes two other categories as types of lymphoma: multiple myeloma and immunoproliferative diseases. About 90% of lymphomas are non-Hodgkin lymphomas. Leukemia is a group of cancers that usually start in the bone marrow and result in high numbers of abnormal white blood cells. Symptoms may include bleeding and bruising problems, tiredness, fever, and increased risk of infections. These symptoms appear due to a lack of normal blood cells. Diagnosis is usually made by blood tests or bone marrow biopsy. There are four main types of leukemia: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML). English), as well as a number of less common types. Treatment of leukemias and lymphomas can involve one or more of chemotherapy, radiation therapy, targeted therapy, and surgery (and bone marrow transplantation in the case of leukemias). The success of leukemia treatment depends on the type of leukemia and the person's age. The outcome of lymphoma treatment depends on the subtype, with some being curable and treatments prolonging survival in most cases. A number of chemotherapeutic agents have previously been used for the treatment of leukemias, including prednisone, vincristine, anthracyclines, L-asparaginase, i cci η / ηζηζ / Ε / γ cyclophosphamide, methotrexate, 6-mercaptopurine, fludarabine, pentostatin, and cladribine. Chemotherapeutic agents for the treatment of lymphomas include cyclophosphamide, hydroxydaunorubicin (also known as doxorubicin or adriamycin), oncovin (vincristine), prednisone, prednisolone, bleomycin, dacarbazine, etoposide, and procarbazine. Combination chemotherapy involves treating a patient with two or more different drugs simultaneously. Drugs may differ in their mechanisms and side effects. The greatest advantage of this therapy is to minimize the chances of developing resistance to any of the agents. Also, the drugs can often be used in lower doses, reducing toxicity. Combination therapies for the treatment of Hodgkin's disease include MOPP (mustine, vincristine, procarbazine, prednisolone) and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Combination therapies for the treatment of non-Hodgkin lymphoma include CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone). Given the number of drugs known for the treatment of leukemias and lymphomas, the number of permutations and combinations of possible drug therapies is clearly large. Furthermore, the mentioned combination therapies do not include antibodies. However, there remains a need for new treatments for leukemias and lymphomas, and particularly for effective combination therapies. Lymphocyte antigen 75 acts as an endocytic receptor to direct captured antigens from the extracellular space to a specialized antigen-processing compartment and is thought to cause a reduction in B-lymphocyte proliferation. Expression of lymphocyte antigen 75 has been observed in cancers pancreatic, ovarian, breast, colorectal, esophageal, skin, thyroid, and lung (non-small cell) as well as Multiple Myeloma and many different subtypes of lymphomas and leukemias. WO2009 / 061996 describes isolated monoclonal antibodies which bind to human DEC-205 (LY75) and related antibody-based molecules and compositions. Pharmaceutical compositions comprising the antibodies are also described, as well as therapeutic and diagnostic methods for using the antibodies. WO2008 / 104806 describes affinity reagents capable of binding to LY75 for use in the treatment or prophylaxis of cancer. WO2015 / 052537 discloses specific isolated antibodies capable of binding to LY75 and their use in the treatment of various cancers. Venetoclax is a small molecule oral drug that blocks B-cell lymphoma anti-apoptotic protein 2 (Bcl-2), causing programmed cell death. It is indicated for chronic lymphocytic leukemia (CLL) in patients with a specific chromosomal abnormality (17p deletion). In 2015, the US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to Venetoclax for subjects with CLL who have relapsed or been refractory to prior treatment and have the i ccc i η / ηζηζ / Ε / γίΛΐ 17p deletion gene mutation. It has now been discovered that combinations of certain anti-LY75 antibodies with Venetoclax demonstrated synergistic results in the treatment of lymphomas. BRIEF DESCRIPTION OF THE INVENTION In one aspect, the invention provides a pharmaceutical composition comprising: (A) an anti-LY75 antibody, or antigen-binding portion thereof, which competes for binding to LY75 with an antibody comprising a variable chain region heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 2; or an anti-LY75 antibody or an antigen-binding portion thereof, said antibody comprising: a) a heavy chain variable region comprising: i) a first vhCDR comprising SEQ ID NO: 5; ii) a second vhCDR comprising SEQ ID NO: 6; and iii) a third vhCDR comprising SEQ ID NO: 7; and b) a light chain variable region comprising: i) a first vICDR comprising SEQ ID NO: 8; ii) a second vICDR comprising SEQ ID NO: 9; and iii) a third vICDR comprising SEQ ID NO: 10; optionally where any one or more of the mentioned SEQ ID NOs independently comprises one, two, three, four or five amino acid substitutions, additions or deletions; and (B) Venetoclax or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical combination is in the form of a combined preparation for simultaneous, separate, or sequential use. In one embodiment, the anti-LY75 antibody or an antigen-binding portion thereof comprises a heavy chain variable region comprising 1, 2, or 3 CDRs selected from the group consisting of CDRs comprising SEQ ID NOs: 5, 6, and 7, and / or a light chain variable region comprising 1, 2 or 3 CDRs selected from the group consisting of CDRs comprising SEQ ID NOs: 8, 9 and 10. In some embodiments, anti-LY75 antibodies bind to LY75 (SEQ ID NO: 15) and are capable of being internalized by a cell expressing LY75. In another embodiment, the anti-LY75 antibody comprises the heavy and / or light chain complementarity determining regions (CDRs) or variable regions (VRs) of the particular antibody described in this invention. (for example, referred to in this invention as "LY75_A1"). Thus, in one embodiment, the i cci η / ηζηζ / Ε / γ antibody comprises the CDR1, CDR2, and CDR3 domains of the heavy chain variable region (VH) of antibody LY75_A1 having the sequence shown in SEQ ID NO:1, and / or the CDR1, CDR2 and CDR3 domains of the LY75_A1 light chain variable region (VL) having the sequence shown in SEQ ID NO:2 . In another embodiment, anti-LY75 antibodies bind to human LY75 and include a heavy chain variable region comprising SEQ ID NO: 1, and / or conservative sequence modifications thereof. The antibody may further include a light chain variable region comprising SEQ ID NO: 2, and / or conservative sequence modifications thereof. In a further embodiment, the anti-LY75 antibodies bind to human LY75 and include a heavy chain variable region and a light chain variable region including the amino acid sequences set forth in SEQ ID NOs: 1 and / or 2, respectively, and their conservative sequence modifications. Antibodies which include heavy and light chain variable regions that are at least 80%, or at least 85%, or at least 90%, or at least 91%, or at least 92%, or by at least 93%, or at least 94%, or at least 95%, or at least 96%, or at least 97%, or at least 98%, or at least 99%, or more than sequence identity to any of the aforementioned sequences are also included in the present invention. Intermediate ranges of the aforementioned values, for example heavy and light chain variable regions having at least 80-85%, 85-90%, 90-95% or 95-100% sequence identity to any of the aforementioned sequences are also intended to be included in the present invention. In one embodiment, the anti-LY75 antibody comprises a heavy chain variable region comprising SEQ ID NO:1 or a sequence that is at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 1. In another embodiment, the anti-LY75 antibody comprises a light chain variable region comprising SEQ ID NO: 2 or a sequence that is at least 80%, at least 85%, at least at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98 %, or at least 99% identical to SEQ ID NO: 2. In another embodiment, the anti-LY75 antibody comprises a heavy chain framework region comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, for at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identical to the chain variable region structure heavy of i ccci η / ηζηζ / Ε / γ SEQ ID NO: 1 as shown in SEQ ID NOS: 16, 17, 18 and 19. In another embodiment, the anti-LY75 antibody comprises a light chain framework region comprising an amino acid sequence that is at least 80 %, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identical to the structure of the light chain variable region of SEQ ID NO:2 as shown in SEQ ID NOS: 20, 21, 22 and 23. In a further embodiment, the anti-LY75 antibody comprises a heavy chain comprising SEQ ID NO: 38 or a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 38. In another embodiment, the anti-LY75 antibody comprises a light chain comprising SEQ ID NO: 39 or a sequence that is at least 80%, at least 85%, at least 90%, at least least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99 % identical to SEQ ID NO: 39. The heavy chain may comprise the sequences of SEQ ID NO: 5-7 or 1. The light chain may comprise the sequences of SEQ ID NO: 8-10 or 2. In one embodiment, the anti-LY75 antibody competes for binding to LY75 with an antibody comprising heavy and / or light chain variable regions comprising the amino acid sequences set forth in SEQ ID NOs:1 and 2, respectively, or the sequences of amino acids at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identical thereto. In another embodiment, the anti-LY75 antibody competes for binding to LY75 with an antibody comprising heavy and / or light chain variable regions comprising the amino acid sequences set forth in SEQ ID NOs:1 and 2 (LY75_A1). Other antibodies of the invention bind to the same epitope or to an epitope on LY75 recognized by the antibodies described in this invention. In another particular modality, the antibody binds to an epitope on LY75 recognized by an antibody that comprises heavy and / or light chain variable regions comprising the amino acid sequences set forth in SEQ ID NOs:1 and 2, respectively, or sequences of amino acids at least 80% identical thereto. In another embodiment, the antibody binds to an epitope on LY75 recognized by an antibody comprising heavy and / or light chain variable regions comprising the amino acid sequences set forth in SEQ ID NOs:1 and 2(LY75_A1). In a further embodiment, anti-LY75 antibodies specifically bind to one i cci η / ηζηζ / Ε / γ or more, eg, 2, 3, 4, 5, 6, 7, 8, 9, or 10, selected peptides from the group comprising SEQ ID NOs: 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36 or 37 or their fragments, where said fragments comprise at least 2, at least at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 contiguous amino acids. In a further embodiment, the epitope recognized by the anti-LY75 antibodies comprises one or more peptides, two or more, or three or more peptides selected from the group consisting of SEQ ID NOs: 27, 29, 30, 34, 35, 36 or 37 or its fragments where said fragments comprise at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9 or at least least 10 contiguous amino acids. In a further embodiment, the epitope recognized by the anti-LY75 antibodies comprises one or more peptides, two or three peptides selected from the group consisting of SEQ ID NOs: 30, 36 and 37 or their fragments where said fragments comprise at least 2 , at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 contiguous amino acids. In a further embodiment, anti-LY75 antibodies comprise variable CDRs compared to the parental antibodies described in this invention. Thus, variant antibodies comprise variant variable regions of a parent antibody, where the parent antibody comprises a first vhCDR comprising SEQ ID NO:5, a second vhCDR comprising SEQ ID NO: 6, a third vhCDR comprising SEQ ID NO: :7, a first vICDR comprising SEQ ID NO:8, a second vICDR comprising SEQ ID NO:9 and a third vICDR comprising SEQ ID NQ:10, and where the variant antibody has 1, 2, 3, 4 , 5 or 6 amino acid substitutions collectively across the pool of first vhCDR, second vhCDR, third vhCDR, first vICDR, second vICDR, and third vICDR, with between 1-4, 1-3, or 1-2 substitutions of particular use, and where the antibody retains specific binding to LY75. All antibodies disclosed herein can be full length, for example, any of the following isotypes: IgG1, IgG2, IgG3, IgG4, IgM, IgA1, IgA2, IgAsec, IgD, and IgE. Alternatively, the antibodies may be fragments such as an antigen-binding moiety or a single chain antibody (eg, a Fab, F(ab')2, Fv, a single chain Fv fragment, a complementarity determining region ( CDR) isolated or a combination of two or more CDRs isolated). The antibodies can be any class of antibody, including, but not limited to, human, humanized, and chimeric antibodies. In other embodiments, the anti-LY75 antibodies are in the form of an immunoconjugate (ie, they further include a covalently linked portion). In i ccci η / ηζηζ / Β / γ a particular modality, the moiety is a drug, such as a maytansinoid, a dolastatin, an auristatin, a trichothecene, a calicheamicin, CC1065 or its derivatives. In a preferred embodiment, the drug portion is DM1 or DM4. In one embodiment, the LY75 antibody comprises a heavy chain variable region and a light chain variable region encoded by nucleic acid sequences comprising SEQ ID NOs: 3 and 4, respectively, or nucleic acid sequences having at least 85 %, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to acid sequences aforementioned nucleic acids which differ from SEQ ID NOs: 3 and 4 due to the degeneracy of the genetic code. In a further aspect there is provided a method of treating cancer in a patient comprising simultaneously, sequentially or separately administering to a patient in need thereof therapeutically effective amounts of components (A) and (B) of a pharmaceutical combination of the invention. In a further aspect of the present invention there is provided a pharmaceutical combination of the invention for use in the treatment of cancer. Further provided is the use of components (A) and (B) as defined herein, in the manufacture of a pharmaceutical combination for simultaneous, separate or sequential use for the treatment of cancer. In one embodiment, the cancer is preferably leukemia or lymphoma. In some modalities, the cancer is selected from the group consisting of non-Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL), B-cell lymphoma, Follicular lymphoma, Mantle cell lymphoma, Mucosa-associated lymphoid tissue lymphoma ( MALT), Histiocyte-Rich B-Cell / T-Cell Lymphoma, Burkitt Lymphoma, Lymphoplasmacytic Lymphoma, Small Lymphocytic Lymphoma, Marginal Zone Lymphoma, T-Cell Lymphoma, Peripheral T-Cell Lymphoma, Lymphoma Anaplastic Large Cell and Angioimmunoblastic T-cell Lymphoma, Acute Myeloid Leukemia, and Chronic Lymphocytic Leukemia. More preferably, the cancer is DLBCL or non-Hodgkin's lymphoma. Also within the scope of the invention are kits comprising a pharmaceutical combination of the invention and, optionally, instructions for use. The kit may further contain at least one additional reagent or one or more additional antibodies. Other features and advantages of the present invention will be apparent from the following detailed description and claims. BRIEF DESCRIPTION OF THE DRAWINGS FIGURE 1 illustrates the alignment of the heavy chain of LY75_A1 (SEQ ID NO:1), the human VH 3-15 germline (SEQ ID NO:11) and the human JH4 germline (SEQ ID NO:12). ). The CDR regions of the LY75_A1 heavy chain are underlined. i ccci η / ηζηζ / Ε / γ FIGURE 2 illustrates the alignment of the LY75_A1 light chain (SEQ ID NO:2), the human VK 012 Germline (SEQ ID NO:13) and the human JK4 Germline (SEQ ID NO:14). The CDR regions of the LY75_A1 light chain are underlined. FIGURE 3A illustrates the cytotoxic activity of DM1-conjugated anti-LY75 monoclonal antibodies on HT-29 and shows that while most antibodies bind LY75 only a few exhibit efficacy. FIGURE 3B illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 on HT-29. FIGURE 30 illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 in RAJL cells. FIGURE 3D illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 in Namalwa cells. FIGURE 3E illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 in Karpas 299 cells. FIGURE 3F illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 on BxPC3 cells. FIGURE 3G illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 on HupT4 cells. FIGURE 3H illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 on HPAFFII cells. FIGURE 3I illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 in EHEB cells. FIGURE 3J illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 on Mec-1 cells. FIGURE 3K illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 on AML-193 cells. FIGURE 3L illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 on HCC 70 cells. FIGURE 3M illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 in HCC 1806 cells. FIGURE 3N illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 in MDA-MB-468 cells. FIGURE 30 illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 on RT4 cells. FIGURE 3P illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 in 5637 cells. i ccci η / ηζηζ / Β / γ FIGURE 3Q illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 in SW780 cells. FIGURE 3R illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 on SCC-9 cells. FIGURE 3S illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 on OE 19 cells. FIGURE 3T illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 on OVCAR-3 cells. FIGURE 3U illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 on SK-OV-3 cells. FIGURE 3V illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 on MOLP-8 cells. FIGURE 3W illustrates the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 or DM4 in RPMI8226 cells. FIGURE 4A illustrates the efficacy of anti-LY75 antibodies conjugated to DM1 or DM4 in the SCID mouse xenograft model of Raji Burkitt lymphoma. FIGURE 4B illustrates the efficacy of anti-LY75 antibodies conjugated to DM1 or DM4 in SCID mouse xenograft model of Burkitt Namalwa lymphoma. FIGURE 4C illustrates the efficacy of anti-LY75 antibodies conjugated to DM1 or DM4 in athymic nude mouse xenograft model of HPAFII pancreatic adenocarcinoma. FIGURE 4D illustrates the efficacy of anti-LY75 antibodies conjugated to DM1 or DM4 in the SCID mouse xenograft model of SW780 human bladder carcinoma. FIGURE 4E illustrates the efficacy of anti-LY75 antibodies conjugated to DM1 or DM4 in the MDA-MB-468 athymic nude mouse xenograft model. FIGURE 4F illustrates the efficacy of anti-LY75 antibodies conjugated to DM1 or DM4 in the athymic nude mouse xenograft model of COLO205 colorectal adenocarcinoma. FIGURE 5A shows the competitive binding of anti-LY75-mAb and an anti-LY75-mAb conjugated to MCC-DM1. FIGURE 5B shows the non-competitive binding of LY75 A1 and an anti-LY75-mAb conjugated to MCC-DM1. FIGURES 6A-6J show graphical representations of LY75_A1 antibody binding to LY75 peptides on a peptide microarray. FIGURE 7 shows an amino acid alignment of peptides bound by the LY75_A1 antibody in the peptide microarray assay and in the peptide interaction and precipitation ("pull down") assay. The highlighted peptides are those with i cci η / ηζηζ / Ε / γ probabilities of forming the epitope recognized by the LY75_A1 antibody. FIGURE 8 shows an algebraic estimation plot: CL vs Fractional Effect of different doses of LY75_DM4 in combination with Venetoclax on the U2932 ABCDLBCL cell line. FIGURE 9 shows an algebraic estimation plot: OI vs. fractional effect of different doses of LY75DM4 in combination with Venetoclax on the HBL-1 ABC-DLBCL cell line. FIGURE 10 shows an algebraic estimation plot: OI vs. fractional effect of different doses of LY75_DM4 in combination with Venetoclax on the HBL-1 ABC-DLBCL cell line. FIGURE 11 shows an algebraic estimation plot: Cl vs. fractional effect of different doses of LY75DM4 in combination with Venetoclax on the TMD8 ABC-DLBCL cell line. DETAILED DESCRIPTION OF THE INVENTION The present disclosure relates to pharmaceutical combinations comprising components (A) and (B) as defined herein, where the pharmaceutical combination is in the form of a combined preparation for simultaneous, separate or sequential use. Component (A) is related to an anti-LY75 antibody as defined herein. Component (B) relates to Venetoclax or one of its pharmaceutically acceptable salts. An example of the LY75 protein is given in SEQ ID NO: 15 herein. The terms "anti-LY75 antibodies" and "LY75 antibodies" are used interchangeably herein. The LY75 antibodies disclosed herein can be internalized when contacted with cells expressing the LY75 receptor. As discussed herein, the LY75 receptor is overexpressed and / or differentially expressed on certain cancer cells, including but not limited to leukemia, preferably acute myeloid leukemia or chronic lymphocytic leukemia, lymphoma, preferably DLBCL, B-Cell Lymphoma, Follicular Lymphoma. , Mantle Cell Lymphoma, Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma, Histiocyte-Rich B-Cell / T-Cell Lymphoma, Burkitt's Lymphoma, Lymphoplasmacytic Lymphoma, Small Cell Lymphocytic Lymphoma, Marginal Zone Lymphoma, Cell Lymphoma T, Peripheral T-Cell Lymphoma, Anaplastic Large Cell Lymphoma, and Angioimmunoblastic T-Cell Lymphoma. As such, when the LY75 antibodies disclosed herein are conjugated to drugs (sometimes referred to in this invention as "antibody-drug conjugates" or "ADCs"), internalization of these ADC molecules into cancer cells results in cell death and hence the tumor treatment. i ccci η / ηζηζ / Ε / γ Anti-LY75 antibodies possess particular structural features such as CDR regions with particular amino acid sequences. Disclosed herein is a set of CDRs that can form an affinity reagent, eg an antibody, which exhibits binding to LY75. Any of the anti-LY75 antibodies of the invention may be isolated antibodies. Thus, the disclosure provides antibodies, preferably isolated antibodies (which, as discussed below, include a wide variety of well-known antibody structures, derivatives, mimetics, and conjugates), nucleic acids encoding combinations of antibodies, host cells used to prepare combinations of antibodies, methods of preparing combinations of antibodies, and pharmaceutical combinations comprising the antibodies and optionally a pharmaceutical carrier, methods of treatment comprising the use of pharmaceutical combinations, and the use of the pharmaceutical combinations for the treatment of cancers. Lymphocyte antigen 75 acts as an endocytic receptor to direct captured antigens from the extracellular space to a specialized antigen-processing compartment and is thought to cause a reduction in B-lymphocyte proliferation. According to SWISS-PROT, lymphocyte antigen 75 is expressed on lymphocytes of the spleen, thymus, colon, and peripheral blood. It has been detected in myeloid and B-lymphoid cell lines. The isoforms designated herein as OGTA076b and OGTA076C are expressed in malignant Hodgkin lymphoma cells called Hodgkin and Reed-Sternberg (HRS) cells. LY75 acts as an endocytic receptor to direct captured antigens from the extracellular space to a specialized antigen-processing compartment. They cause a reduction in the proliferation of B lymphocytes. LY75 expression has been observed in pancreatic, bladder, ovarian, breast (including triple negative), colorectal, esophageal, skin, thyroid, and lung (non-small cell) cancers as well as multiple myeloma and many different subtypes of lymphomas (including DLBCL) and leukemias. The anti-LY75 antibody can, in certain cases, cross-react with LY75 from a species other than human. For example, to facilitate clinical trials, anti-LY75 antibodies can cross-react with murine or primate LY75 molecules. Alternatively, in certain embodiments, the antibodies may be fully specific for human LY75 and may not exhibit non-human species or other cross-reactivity. Antibodies that are useful in the present invention can take a number of formats as described herein, including traditional antibodies as well as antibody derivatives, fragments, and mimetics, described below. In one embodiment, the invention provides antibody structures that contain a set of 6 CDRs as defined herein (including small amounts of amino acid changes as described below). "Antibody" in the present context includes a wide variety of structures, as will be appreciated by those in the art, which in some embodiments contain at least a set of 6 CDRs as defined herein; including, but not limited to, traditional antibodies (including both monoclonal and polyclonal antibodies), humanized and / or chimeric antibodies, antibody fragments, genetically engineered antibodies (for example, with amino acid modifications as described above). below), multispecific antibodies (including bispecific antibodies), and other analogs known in the art. Traditional antibody structural units typically comprise a tetramer. Each tetramer is generally composed of two identical pairs of polypeptide chains, each pair having a "light" chain (typically having a molecular weight of about 25 kDa) and a "heavy" chain (usually having a molecular weight of about 50 kDa). -70 kDa). Human light chains are classified as kappa and lambda light chains. Heavy chains are classified as mu, delta, gamma, alpha, or epsilon, and define the isotype of the antibody as IgM, IgD, IgG, IgA, and IgE, respectively. IgG has several subclasses, including, but not limited to, lgG1, lgG2, lgG3, and lgG4. IgM has subclasses, including, but not limited to, lgM1 and lgM2. Therefore, "isotype" in the present context means any of the immunoglobulin subclasses defined by the chemical and antigenic characteristics of their constant regions. Known human immunoglobulin isotypes are IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM1, IgM2, IgD, and IgE. It should be understood that therapeutic antibodies can also comprise hybrids of any combination of isotypes and / or subclasses. In many embodiments, IgG isotypes are used in the present invention, with IgG 1 having particular use in a number of applications. The amino terminal portion of each chain includes a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. In the variable region, three loops are joined together for each of the heavy chain and light chain V domains to form an antigen binding site. Each of the loops is referred to as a complementarity determining region (hereinafter referred to as a "CDR'j", where the variation in amino acid sequence is more significant. "Variable" refers to the fact that certain segments of the variable region differ widely in sequence between antibodies Variability within the variable region is not evenly distributed Instead, V regions consist of relatively invariant stretches called framework regions (FRs) i cci η / ηζηζ / Ε / γ of 15-30 amino acids separated by shorter regions of extreme variability called "hypervariable regions" that are each 9-15 amino acids or longer in length. Each VH and VL is composed of three hypervariable regions (“complementarity determining regions,” “CDRs”) and four FRs, arranged between the amino terminus and the carboxy terminus in the following order: FR1-CDR1-FR2-CDR2-FR3- CDR3-FR4. The hypervariable region generally encompasses amino acid residues between about amino acid residues 24-34 (LCDR1; "L" denotes light chain), 5056 (LCDR2), and 89-97 (LCDR3) in and around the light chain variable region. approximately 31-35B (HCDR1; "H" denotes heavy chain), 50-65 (HCDR2), and 95-102 (HCDR3) in the heavy chain variable region; Kabat et al, SEQUENCES OF PROTEINS OF IMMUNOLOGICAL INTEREST, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991) and / or those residues that form a hypervariable loop (eg residues 26-32 (LCDR1 ), 50-52 (LCDR2) and 91-96 (LCDR3) in the light chain variable region and 26-32 (HCDR1), 53-55 (HCDR2) and 96-101 (HCDR3) in the heavy chain variable region Chothia and Lesk (1987) J. Mol Biol 196:901-917 Specific CDRs of the invention are described below. Throughout this specification, the Kabat numbering system is generally used when referring to a residue in the variable domain (approximately, residues 1-107 of the light chain variable region and residues 1113 of the heavy chain variable region) (eg, Kabat et al., supra (1991)). CDRs contribute to the formation of the antigen-binding site, or more specifically, the epitope-binding site of antibodies. The term "epitope" or "antigenic determinant" refers to a site on an antigen to which an immunoglobulin or antibody specifically binds. Epitopes can be formed from either contiguous amino acids or non-contiguous amino acids juxtaposed by tertiary folding of a protein. Epitopes formed from contiguous amino acids are typically retained upon exposure to denaturing solvents, whereas epitopes formed by tertiary folding are typically lost upon treatment with denaturing solvents. An epitope typically includes at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acids in a single spatial conformation. As described herein, methods for determining which epitopes are bound by a given antibody (i.e., epitope mapping) are well known in the art and include, for example, immunoblotting and immunoprecipitation assays, where overlapping peptides or LY75 flanks are tested for reactivity with the given anti-LY75 antibody. Methods for determining the spatial conformation of epitopes include techniques in the art and those described in this invention, for example, X-ray crystallography and two-dimensional nuclear i cci η / ηζηζ / Ε / γ magnetic resonance (see, for example, Epitope Mapping Protocols in Methods in Molecular Blology, Vol. 66, G. E. Morris, Ed. (1996)). The term "epitope mapping" refers to the process of identifying the molecular determinants for antibody-antigen recognition. The carboxy terminal portion of each chain defines a constant region primarily responsible for effector function. Kabat et al. collected numerous primary sequences from the variable regions of heavy chains and light chains. Based on the degree of sequence conservation, they classified individual primary sequences into CDR and structure and listed them (see SEQUENCES OF IMMUNOLOGICAL INTEREST, 5th Edition, NIH Publication No. 91-3242, E.A. Kabat et al. .). In the IgG subclass of immunoglobulins, there are several immunoglobulin domains in the heavy chain. By "immunoglobulin (lg) domain" in this invention is meant a region of an immunoglobulin that has a distinctive tertiary structure. Of interest in the present invention are heavy chain domains, including constant heavy (OH) chain domains and hinge domains. In the context of IgG antibodies, the IgG isotypes each have three OH regions. Accordingly, "OH" domains in the context of IgG are as follows: "CH1" refers to positions 118220 according to the EU index as in Kabat. “CH2” refers to positions 237-340 according to the EU index as in Kabat, and “CH3” refers to positions 341-447 according to the EU index as in Kabat. Another type of heavy chain lg domain is the hinge region. By "hinge" or "hinge region" or "antibody hinge region" or "immunoglobulin hinge region" in this invention is meant the flexible polypeptide comprising the amino acids between the first constant domain and the second constant domain of an antibody. Structurally, the IgG CH1 domain ends at position EU 220, and the IgG CH2 domain begins at residue position EU 237. Therefore for IgG the antibody hinge is defined in this invention as including positions 221 (D221 in lgG1) up to 236 (G236 in lgG1), where the numbering is according to the EU index as in Kabat. In some embodiments, for example in the context of an Fe region, the bottom hinge is included, with "bottom hinge" generally referring to positions 226 or 230. Of particular interest in the present invention are the Fe regions. By "Fe" or "Fe region" or "Fe domain" in the present context is meant the polypeptide comprising the constant region of an antibody excluding the first immunoglobulin domain. constant region and in some cases, part of the hinge. Hence Fe refers to the last two constant region immunoglobulin domains of IgA, IgD, and IgG, the last three constant region immunoglobulin domains of IgE and IgM, and the flexible hinge i ccc i n / nznz / E / YiAi N-terminal to these domains. For IgA and IgM, Fe may include the J chain. For IgG, the Fe domain comprises the immunoglobulin domains Cy2 and Cy3 (Cy2 and Cy3) and the lower hinge region between Cy1 (Cy1) and Cy2 (Cy2). Although the boundaries of the Fe region may vary, the human IgG heavy chain Fe region is generally defined as including residues C226 or P230 at its carboxyl terminus, where numbering is according to the EU index as in Kabat. In some embodiments, as more fully described below, amino acid modifications are made to the Fe region, for example to alter binding to one or more FcyR receptors or to the FcRn receptor. In some embodiments, the antibodies are full length. By "full-length antibody" in this invention is meant the structure constituting the natural biological form of an antibody, including variable and constant regions, including one or more modifications as set forth in this invention. Alternatively, antibodies can be a variety of structures, including, but not limited to, antibody fragments, monoclonal antibodies, bispecific antibodies, minibodies, domain antibodies, synthetic antibodies (sometimes referred to in this invention as "antibody mimetics"), chimeric antibodies, humanized antibodies, antibody fusions (sometimes referred to as "antibody conjugates"), and fragments of each, respectively. Structures that are based on the use of a set of CDRs are included within the definition of "antibody". In one embodiment, the antibody is an antibody fragment. Specific antibody fragments include, but are not limited to, (i) the Fab fragment consisting of the VL, VH, CL, and CH1 domains, (ii) the Fd fragment consisting of the VH and CH1 domains, (iii) the Fv fragment consisting of the VL and VH domains of a single antibody; (iv) the dAb fragment (Ward et al., 1989, Nature 341:544-546, wholly incorporated by reference) which consists of a single variable region, (v) isolated CDR regions, (vi) F(ab) fragments ')2, a bivalent fragment comprising two linked Fab fragments (vii) single chain Fv (scFv) molecules, where a VH domain and a VL domain are linked by a peptide linker which allows the two domains to associate for form an antigen binding site (Bird et al., 1988, Science 242:423-426, Huston et al., 1988, Proc. Nati. Acad. Sci. U.S.A. 85:5879-5883, fully incorporated by reference), (viii) bispecific single chain Fv (WO 03 / 11161, incorporated herein by reference) and (ix) "diabodies" or "triabodies", multivalent or multispecific fragments constructed by gene fusion (Tomlinson et al. , 2000, Methods Enzymol. 326:461-479; WO94 / 13804; Holliger et al., 1993, Proc. Nati. Acad. Sci. U.S.A. 90:6444-6448, all of these documents are incorporated in their entirety by reference). In some embodiments, the antibody may be a mixture of different species, i ccc i η / ηζηζ / Ε / γίΛΐ for example a chimeric antibody and / or a humanized antibody. That is, in the present invention, the CDR arrays may be used with framework regions and constants other than those specifically described by sequence in this invention. In general, both "chimeric antibodies" and "humanized antibodies" refer to antibodies that combine regions from more than one species. For example, "chimeric antibodies" traditionally comprise variable regions from a mouse (or rat, in some cases) and the constant region(s) from a human. "Humanized antibodies" generally refer to non-human antibodies that have had the variable domain framework regions exchanged for sequences found in human antibodies. In general, in a humanized antibody, the entire antibody, except for the CDRs, is encoded by a polynucleotide of human origin or is identical to such an antibody except within its CDRs. CDRs, some or all of which are encoded by nucleic acids originating in a non-human organism, are grafted onto the beta-sheet structure of a human antibody variable region to create an antibody, the specificity of which is determined by the grafted CDRs. The creation of such antibodies is described in, for example, WO 92 / 11018, Jones, 1986, Nature 321:522-525, Verhoeyen et al., 1988, Science 239:1534-1536, all of which are incorporated in their entirety. for reference. "Backmutation" of selected acceptor framework residues to the corresponding donor residues is frequently required to regain affinity that is lost in the initial grafted construct (US 5530101; US ​​5585089; US 5693761; US ​​5693762; US 6180370; US 5859205; US 5821337; US 6054297; US 6407213, all of these documents are incorporated by reference in their entirety). The optimally humanized antibody will also comprise at least a portion of an immunoglobulin constant region, typically that of a human immunoglobulin, and thus will typically comprise a human Fe region. Humanized antibodies can also be generated using mice with a genetically engineered immune system. Roque et al., 2004, Biotechnol. Prog. 20:639-654, incorporated in its entirety by reference. A variety of techniques and methods for humanizing and remodeling non-human antibodies are well known in the art (See Tsurushita & Vasquez, 2004, Humanization of Monoclonal Antibodies, Molecular Biology of B Cells, 533-545, Elsevier Science (U.S.A.), and the references cited in said document, all incorporated in their entirety by reference). Humanization methods include, among others, the methods described in Jones et al., 1986, Nature 321:522-525; Riechmann et al.,1988; Nature 332:323-329; Verhoeyen et al., 1988, Science, 239:1534-1536; Queen et al., 1989, Proc Nati Acad Sci, USA. 86:10029-33; He et al., 1998, J. Immunol. 160: 1029-1035; Carter et al., 1992, Proc Nati Acad Sci E.U.A. 89:4285-9, Presta et al., 1997, Cancer Res. 57(20):4593-9; Gorman et al., 1991, Proc. nati. Acad. Sci. U.S.A. 88:4181-4185; O'Connor et i cci η / ηζηζ / Ε / γ a / ., 1998, Protein Eng 11:321-8, all incorporated by reference in their entirety. Humanization or other methods to reduce the immunogenicity of non-human antibody variable regions may include surface reshaping methods, as described for example in Roguska et al., 1994, Proc. nati. Acad. Sel. USA 91:969-973, incorporated in its entirety by reference. In one embodiment, the parent antibody has been affinity matured, as is known in the art. Structure-based methods for humanization and affinity maturation may be employed, for example as described in USSN 11 / 004,590. Selection-based methods may be employed to humanize and / or affinity-mature variable regions of antibodies, including but not limited to methods described in Wu et al., 1999, J. Mol. Biol. 294:151-162; Baca et al., 1997, J. Biol. Chem. 272(16):10678-10684; Rosok et al., 1996, J. Biol. Chem. 271(37): 22611-22618; Rader et al., 1998, Proc. nati. Acad. Sel. USA 95: 8910-8915; Krauss et al., 2003, Protein Engineering 16(10):753-759, all incorporated in their entirety by reference. Other humanization methods may involve grafting only portions of the CDRs, including but not limited to methods described in USSN 09 / 810,510; Tan et al., 2002, J. Immunol. 169:1119-1125; De Pascalis et al., 2002, J. Immunol.169:30763084, all incorporated in their entirety by reference. The antibodies disclosed herein can be isolated or recombinant. "Isolated," when used to describe the various polypeptides described in this invention, means a polypeptide that has been identified and separated and / or recovered from a cell or cell culture from which it was expressed. Thus, an isolated antibody is intended to refer to an antibody that is substantially free of other antibodies that have different antigen specificities (for example, an isolated antibody that specifically binds LY75 is substantially free of antibodies that specifically bind antigens). other than the LY75). Thus, an "isolated" antibody is one found in a form not normally found in nature (eg non-naturally occurring). An isolated antibody as defined in this invention can include, in one embodiment, at least one amino acid which is not present in the "natural" presenting antibody. This amino acid can be introduced by means of addition or substitution. It will be understood that the introduced amino acid may be a naturally occurring or non-naturally occurring amino acid. In some embodiments, the antibodies of the invention are recombinant proteins, isolated proteins, or substantially pure proteins. An "isolated" protein is not accompanied by at least some of the material with which it is normally associated in its natural state, for example constituting at least about 5%, or at least about 50% by weight of the total protein in a given sample. It is understood that the isolated protein can constitute between 5 and 99.9% by weight of the total protein content depending on the circumstances. For example, the i ccc i n / nznz / E / YiAi protein can be made at a significantly higher concentration through the use of an inducible promoter or high expression promoter, so that the protein is made at increased levels of concentration. . In the case of recombinant proteins, the definition includes the production of an antibody in a wide variety of organisms and / or host cells that are known in the art where it is not naturally produced. Commonly, an isolated polypeptide will be prepared by at least one purification step. An "isolated antibody" refers to an antibody which is substantially free of other antibodies having different antigenic specificities. For example, an isolated antibody that specifically binds to LY75 is substantially free of antibodies that specifically bind to non-LY75 antigens. The isolated anti-LY75 antibody can, of course, associate with Venetoclax. Isolated monoclonal antibodies, having different specificities, can be combined in a well-defined composition. Accordingly, by way of example, the antibody of the invention may be optionally and individually included or excluded in a formulation, as further described below. The anti-LY75 antibodies of the present invention specifically bind to LY75 (eg SEQ ID NO: 15). "Specific binding" or "binds specifically to" or is "specific for" a particular antigen or epitope means binding that is measurably different from a non-specific interaction. Specific binding can be measured, for example, by determining the binding of one molecule in comparison to the binding of a control molecule, which is generally a similarly structured molecule that has no binding activity. For example, specific binding can be determined by competition with a control molecule that is similar to the target. Specific binding for a particular antigen or epitope can be exhibited, for example, by an antibody having a KD for an antigen or epitope of at least about 10-4M, at least about 10-5M, at least about 10-6M, at least about 10-7M, at least about 10-8M, at least about 10-9M, alternatively at least about 10-10M, at least about 10"11M, at least about 10 -12M, or greater, where KD refers to a rate of dissociation of a particular antibody-antigen interaction. Typically, an antibody that specifically binds to an antigen will have a KD that is 20, 50, 100, 500, 1000, 5,000, 10,000 or more times greater for a control molecule relative to the antigen or epitope. However, in the present invention, when ADCs of the antibodies against LY75 of the invention are administered, what is important is that the KD be sufficient to cause internalization and therefore cell death without significant side effects. Additionally, specific binding for a particular antigen or epitope can i cci η / ηζηζ / Β / γ be exhibited, for example, by an antibody having a KA or Kafor an antigen or epitope of at least 20, 50, 100 , 500, 1000, 5,000, 10,000 or more times higher for the epitope relative to a control, where KA or Kase refers to a rate of association of a particular antibody-antigen interaction. Standard assays to assess the binding capacity of antibodies to LY75 can be performed on the protein or cellular level and are known in the art, including, for example, ELISAs, Western blots, RIAs, BIAcore® assays, and flow cytometric analysis. . Suitable tests are described in detail in the Examples. The binding kinetics (eg binding affinity) of antibodies can also be assessed by standard assays known in the art, such as by Biacore® system analysis. To assess binding to tumor cells of Raji or Daudi B cells, Raji (ATCC Deposit N2 CCL-86) or Daudi (ATCC Deposit N2 CCL-213) cells can be obtained from publicly available sources, such as the American Collection of Typed Cultures (“American Type Culture Collection”), and used in standard assays, such as flow cytometric analysis. LY75 antibodies that bind to LY75 (SEQ ID NO: 15) can be internalized when contacted with cells expressing LY75 on the cell surface. These antibodies are referred to herein as either "anti-LY75 antibodies" or, for ease of description, "anti-LY75 antibodies." Both terms are used interchangeably herein. Antibodies against LY75 are internalized upon contact with cells, particularly tumor cells, which express LY75 on the surface. That is, antibodies against LY75 as defined in this invention that also comprise drug conjugates are internalized by tumor cells, resulting in drug release and subsequent cell death, allowing treatment of cancers that exhibit LY75 expression. Internalization in this context can be measured in various ways. In one embodiment, LY75 antibodies are contacted with cells, such as a cell line as set forth in this invention, using standard assays such as MAbZap. It would be clear to the expert that the MabZap assay is representative of the effect that would be expected to be seen with an antibody-drug conjugate (ADC). In the latter case, the ADC would be internalized, thus taking the drug into the cell. A toxic drug would have the ability to kill the cell, that is, kill the targeted cancer cell. Data from MabZap assays are readily accepted by those skilled in the art as representative of ADC assays (Kohls, M and Lappi, D.,

[2000] Biotechniques, vol. 28, no. 1, 162-165). In these in vitro assay modalities, LY75 antibodies are added, along with an anti-LY75 antibody comprising a toxin; for example, the antibody against i ccci η / ηζηζ / Ε / γ LY75 may be murine or humanized and the anti-LY75 antibody may be anti-murine or anti-humanized and may contain a toxin such as saponin. Upon formation of the [LY75 antibody]-[anti-LY75 antibody-drug conjugate] complex, the complex is internalized and drug (eg saponin) is released, resulting in cell death. Only after internalization is the drug released, and thus cells remain viable in the absence of internalization. As discussed below, without being limited by theory, in therapeutic applications, the anti-LY75 antibody contains the toxin, and upon internalization, the antibody-toxin binding is dissociated, releasing the toxin and killing the toxin. cell. In one embodiment, the anti-LY75 antibody comprises the heavy and light chain complementarity determining regions (CDRs) or variable regions (VRs) of the particular antibody described in this invention (eg, referred to herein as "LY75_A1"). Accordingly, in one embodiment, the antibody comprises the CDR1, CDR2, and CDR3 domains of the heavy chain variable region (VH) of antibody LY75_A1 having the sequence shown in SEQ ID NO:1, and the CDR1, CDR2 and CDR3 of the light chain variable region (VL) of the LY75_A1 antibody having the sequence shown in SEQ ID NO:2. In another embodiment, the anti-LY75 antibody comprises a heavy chain variable region comprising a first vhCDR comprising SEQ ID NO: 5; a second vhCDR comprising SEQ ID NO: 6; and a third vhCDR comprising SEQ ID NO:7; and a light chain variable region comprising a first vICDR comprising SEQ ID NO:8; a second vICDR comprising SEQ ID NO: 9; and a third vICDR comprising SEQ ID NQ:10. In another embodiment, the anti-LY75 antibodies of the invention bind to human LY75 and include a heavy chain variable region comprising an amino acid sequence comprising SEQ ID NO: 1, and conservative sequence modifications thereof. The antibody may further include a light chain variable region comprising an amino acid sequence comprising SEQ ID NO: 2, and conservative sequence modifications thereof. In a further embodiment, the anti-LY75 antibodies bind to human LY75 and include a heavy chain variable region and a light chain variable region comprising the amino acid sequences set forth in SEQ ID NOs:1 and / or 2, respectively, and their sequence conservative modifications. In a further embodiment, the anti-LY75 antibodies bind to human LY75 and include a heavy chain and a light chain comprising the amino acid sequences set forth in SEQ ID NO: 38 and / or 39, respectively, and conservative modifications of sequence of them. i ccc i η / ηζηζ / Ε / γίΛΐ In the present context, the term "conservative sequence modification" refers to, for example, the substitution of an amino acid with an amino acid having similar characteristics. It is common knowledge to a person skilled in the art which of these substitutions can be considered conservative. Other modifications which may be considered conservative sequence modifications include, for example, glycosylation. Optionally, one or more of SEQ ID NO: 5-10 independently comprise one, two, three, four or five conservative amino acid substitutions; optionally, one or more of SEQ ID NO: 5-10 independently comprise one or two conservative amino acid substitutions. Preferably, the term "conservative sequence modifications" is considered to include amino acid modifications that do not significantly affect or alter the binding characteristics of the antibody containing the amino acid sequence. Such conservative modifications include amino acid substitutions, additions, and deletions. Modifications can be introduced into an antibody of the invention by means of standard techniques known in the art, such as site-directed mutagenesis and POR-mediated mutagenesis. Conservative amino acid substitutions are those in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (for example, lysine, arginine, histidine), acidic side chains (for example, aspartic acid, glutamic acid), uncharged polar side chains (for example, glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, tryptophan), nonpolar side chains (eg, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine), beta-branched side chains (eg, threonine, valine, isoleucine), and aromatic side chains (eg, example, tyrosine, phenylalanine, tryptophan, histidine). Thus, one or more amino acid residues within the CDR regions of an antibody of the invention may be replaced with other amino acid residues from the same side chain family and the altered antibody assayed for retained function using the functional assays described herein. Isolated antibodies which include heavy and light chain variable regions that are at least 80%, or at least 85%, or at least 90%, or at least 91%, or at least 92%, or at least 93%, or at least 94%, or at least 95%, or at least 96%, or at least 97%, or at least 98%, or at least 99%, or more sequence identity to any of the aforementioned sequences are also included in the present invention. Intermediate ranges to the aforementioned values, for example, heavy chain and light chain variable regions that i cci η / ηζηζ / Ε / γ have at least 80-85%, 85-90%, 90-95% or 95-100% sequence identity to any of the aforementioned sequences are also intended to be encompassed by the present invention. In one embodiment, the anti-LY75 antibody comprises a heavy chain variable region comprising SEQ ID NO:1 or a sequence that is at least 90%, at least 91%, at least 92%, at least 93 %, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 1. In another embodiment, the anti-LY75 antibody comprises a light chain variable region comprising SEQ ID NO:2 or a sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 2. In another embodiment, the anti- LY75 comprises a heavy chain framework region comprising an amino acid sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or po r at least 99% identical in structure to the heavy chain variable region of SEQ ID NO: 1 comprising SEQ ID NOs: 16, 17 and 18. In another embodiment, the anti-LY75 antibody comprises a heavy chain framework region light comprising an amino acid sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96% , at least 97%, at least 98%, or at least 99% identical in structure to the light chain variable region of SEQ ID NO:2 comprising SEQ ID NOs:19, 20 and 21. In a further embodiment, the anti-LY75 antibody comprises a heavy chain comprising SEQ ID NO: 38 or a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 38. In another embodiment, the anti-LY75 antibody comprises a light chain comprising SEQ ID NO: 39 or a sequence that is at least 80%, at least 85%, at least 90%, at least least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99 % identical to SEQ ID NO: 39. The heavy chain may comprise the sequences of SEQ ID NO: 5-7 or 1. The light chain may comprise the sequences of SEQ ID NO: 8-10 or 2. In one embodiment, the anti-LY75 antibody is referred to herein as "LY75_A1 antibody" and comprises the following CDRs, as well as variants containing a limited number of amino acid variants: i ccc i η / ηζηζ / Ε / γίΛΐ A1 SEQ ID NOs heavy variable CDR1 5 heavy variable CDR2 6 heavy variable CDR3 7 light variable CDR1 8 light variable CDR2 9 light variable CDR3 10 i ccci η / ηζηζ / Β / γ Also disclosed herein are variable heavy and light chains comprising the CDR arrays of the invention, as well as full length heavy and light chains (eg comprising constant regions as well). As will be appreciated by those skilled in the art, the anti-LY75 antibody CDR arrays can be incorporated into murine, humanized, or human constant regions (including framework regions). Accordingly, the present disclosure provides variable heavy and light chains and full-length heavy and light chains that are at least about 90%-99% identical to the SEQ IDs described in this invention, with 90, 91, 92, 93, 94, 95, 96, 97, 98 and 99% all useful in the present invention. In some embodiments, the anti-LY 75 antibody is one that competes for binding to human LY 75 with an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 1, and a heavy chain variable region light chain comprising the amino acid sequence set forth in SEQ ID NO: 2. Competing antibodies can be identified using routine techniques. Such techniques include, for example, an immunoassay, which shows the ability of one antibody to block the binding of another antibody to a target antigen, ie, a competitive binding assay. Competitive binding is determined in an assay in which the immunoglobulin under test inhibits the specific binding of a reference antibody to a common antigen, such as LY75. Numerous types of competitive binding assays are known, for example: solid phase direct or indirect radioimmunoassay (RIA), solid phase direct or indirect enzyme immunoassay (EIA), sandwich competition (see Stahli et al., Methods in Enzymology 9:242 (1983)); Solid phase biotin-avidin EIA (see Kirkland et al., J. Immunol. 137:3614 (1986)); solid phase direct labeled assay, solid phase direct labeled sandwich assay (see Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Press (1988)); Solid phase direct label RIA using 1-125 label (see Morel et al., Mol. Immunol. 25(1):7 (1988)); Solid phase direct biotin-avidin EIA (Cheung et al., Virology 176:546 (1990)); and RIA direct labeling. (Moldenhauer et al., Scand. J. Immunol. 32:77 (1990)). Typically, that type of assay involves the use of purified antigen bound to a solid surface or cells bearing any of these, an unlabeled test immunoglobulin, and a labeled reference immunoglobulin. Competitive inhibition is measured by determining the amount of label bound to the solid surface or cells in the presence of the test immunoglobulin. In general the test immunoglobulin is present in excess. In general, when a competitive antibody is present in excess, it will inhibit the specific binding of a reference antibody to a common antigen by at least 50-55%, 55-60%, 60-65%, 65-70%. 70-75% 75-80% 80-85% 85-90% 9095% 95-99% or more. Monoclonal antibodies can be characterized for binding to LY75 using a variety of known techniques. In general, antibodies are initially characterized by ELISA. Briefly, microtiter plates can be coated with purified LY75 in PBS, and then blocked with irrelevant proteins such as bovine serum albumin (BSA) diluted in PBS. Plasma dilutions from LY75-immunized mice are added to each well and incubated for 1-2 hours at 37°C. Plates are washed with PBS / Tween 20 and then incubated with an alkaline phosphatase-conjugated goat anti-human IgG Fc-specific polyclonal reagent for 1 hour at 37°C. After washing, plates are developed with ABTS substrate, and analyzed at an OD of 405. Preferably, mice developing the highest titers will be used for the fusions. An ELISA assay as described above can be used to select for antibodies and thus antibody-producing hybridomas that show positive reactivity with the LY75 immunogen. Hybridomas that bind, preferably with high affinity, to LY75 can then be subcloned and further characterized. A clone of each hybridoma, which retains the reactivity of the parental cells (by ELISA), can then be chosen for preparation of a cell bank, and for purification of antibodies. To purify anti-LY75 antibodies, selected hybridomas can be grown in roller culture bottles, two-liter spinner flasks, or other culture systems. Supernatants can be filtered and concentrated prior to affinity chromatography with protein A-Sepharose (Pharmacia, Piscataway, NJ) to purify the protein. After exchange of buffer to PBS, the concentration can be determined by OD2so using extinction coefficient 1.43 or preferably by nephelometric analysis. IgG can be checked by gel electrophoresis and by the antigen specific method. To determine if selected anti-LY75 monoclonal antibodies bind unique epitopes, each antibody can be biotinylated using commercially available reagents (Pierce, Rockford, IL). Biotinylated MAb binding can be detected with a streptavidin-labeled probe. To determine the isotype of the purified antibodies, isotype ELISAs can be performed using art-recognized techniques. For example, microtiter plate wells can be coated with 10 pg / ml anti-lg overnight at 4°C. After blocking with 5% BSA, plates are reacted with 10 pg / ml monoclonal antibodies or purified isotype controls, at room temperature for two hours. The wells can then be reacted with either IgGI or other isotype-specific conjugate probes. Plates are developed and analyzed as described above. To assay the binding of the monoclonal antibodies to live cells expressing LY75, flow cytometry can be used. Briefly, cell lines and / or human PBMCs expressing membrane-bound LY75 (grown under standard culture conditions) are mixed with various concentrations of monoclonal antibodies in PBS containing 0.1% BSA at 4°C for 1 hour. After washing, cells are reacted with fluorescein-tagged anti-IgG antibody under the same conditions as the primary antibody staining. Samples can be analyzed by a FACScan instrument using light and side scatter properties to bypass single cells and binding of labeled antibodies determined. An alternative assay using fluorescence microscopy can be used (in addition to or instead of) the flow cytometry assay. Cells can be stained exactly as described above and examined by fluorescence microscopy. This method allows visualization of individual cells, although it may have decreased sensitivity depending on the density of the antigen. Anti-LY75 IgGs can be further assayed for reactivity with the LY75 antigen by Western blotting. Briefly, cell extracts from cells expressing LY75 can be prepared and subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis. After electrophoresis, the separated antigens will be transferred to nitrocellulose membranes, blocked with 20% mouse serum, and probed with the monoclonal antibodies to be tested. IgG binding can be detected using anti-IgG alkaline phosphatase and can be developed with BCIP / NBT substrate tablets (Sigma Chem. Co., St. Louis, MO). Methods for analyzing the binding affinity, cross-reactivity, and binding kinetics of various anti-LY75 antibodies include standard assays known in the art, for example, Biacore™ surface plasmon resonance (SPR) analysis. using an SPR Biacore™ 2000 instrument (Biacore AB, Uppsala, Sweden. In one embodiment, the antibody specifically binds to human LY75 comprising SEQ ID NO: 15). Preferably, the anti-LY75 antibody binds to human LY75 with high affinity. Preferably, the anti-LY75 antibody binds to a LY75 protein with a KD of 5 x 10"8M or less, binds to a LY75 protein with a KD of 2 x 10"8M or less, binds to a LY75 protein with a KD of 5 x 10"9M or less, binds to a LY75 protein with a KD of 4 x 10"9M or less, binds to a LY75 protein with a KD of 3 x 10"9M or less, binds to a LY75 protein with a KD of 2 x 10-9M or less, binds to a LY75 protein with a KD of 1 x 10-9M or less, binds to a LY75 protein with a KD of 5 x 10-10M or less, or it binds to a LY75 protein with a KD of 1 x 10-10M or less. In one embodiment, anti-LY75 antibodies compete (eg, cross-compete) for binding to LY75 with the particular anti-LY75 antibodies described herein (eg, LY75_A1). Such competitive antibodies can be identified based on their ability to competitively inhibit the LY75 binding of one or more of the mAbs in standard LY75 binding assays. For example, conventional ELISA assays can be used in which a recombinant human LY75 protein is immobilized on the plate, one of the antibodies is fluorescently labeled, and the ability of unlabeled antibodies to compete with the labeled antibody is assessed for binding. Additionally or alternatively, BIAcore analysis can be used to assess the ability of antibodies to cross compete. The ability of a test antibody to inhibit the binding of an anti-LY75 antibody of the invention to human LY75 demonstrates that the test antibody can compete with the antibody for binding to human LY75. In one embodiment, the competitive antibody is an antibody that binds to the same epitope on human LY75 as the particular anti-LY75 monoclonal antibodies described herein (eg, LY75 A1). Conventional epitope mapping techniques, such as X-ray crystallography and two-dimensional nuclear magnetic resonance, can be used to determine whether an antibody binds to the same epitope as a reference antibody (see, for example, Epitope Mapping Protocols in Methods in Molecular Biology, Vol. 66, G.E. Morris, Ed. (1996)). In one embodiment, the antibody that competes for binding to LY75 and / or binds to the same epitope on human LY75 is a human antibody. Once a unique, archetypal anti-LY75 mAb has been isolated that has the desired properties described in this invention, other mAbs with similar properties, eg, bearing the same epitope can be generated. For example, mice can be immunized with LY75 as described herein, hybridomas can be produced, and the resulting mAbs can be selected for the ability to compete with the archetypal mAb for binding to LY75. Mice can also be immunized with a smaller fragment of LY75 containing the epitope to which the archetypal mAb binds. The epitope can be localized, for example, by selection for binding to a series of overlapping peptides spanning LY75. Alternatively, the method of Jespers et al., Biotechnology 12:899, 1994 can be used to guide the selection of mAbs that have the same epitope and thus similar properties to the archetypal mAb. Using phage display, first the heavy chain of the archetypal antibody is annealed to a repertoire of light chains (preferably human) to select for a LY75-binding mAb, and then the new light chain is annealed to a repertoire of heavy chains (preferably human). ) to select for a LY75-binding mAb (preferably human) that has the same epitope as the archetypal mAb. Alternatively, they can obtain variants of the archetypal mAb by mutagenesis of cDNA encoding the heavy and light chains of the antibody. To assess the level of competition between two antibodies, for example, radioimmunoassays or assays using other antibody labels can be used. For example, a LY75 antigen can be incubated with a saturating amount of a first anti-LY75 antibody or its antigen-binding fragment conjugated to a labeled compound (eg, 3H, 125l, biotin, or rubidium) in the presence of the LY75 antigen. same amount of a second unlabeled anti-LY75 antibody. The amount of labeled antibody that is bound to antigen in the presence of the unlabeled blocking antibody is then assessed and compared to binding in the absence of the unlabeled blocking antibody. Competition is determined by the percent change in binding signals in the presence of the unlabeled blocking antibody compared to the absence of the blocking antibody. Thus, if there is 50% inhibition of labeled antibody binding in the presence of the blocking antibody compared to binding in the absence of the blocking antibody, then there is 50% competition between the two antibodies. Thus, reference to the competition between a first and a second antibody of 50% or more, 60% or more, 70% or more, such as 70%, 71%, 72%, 73%, 74%, 75 %, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more, means that the first antibody inhibits the binding of the second antibody (or vice versa) to the antigen by 50%, 60%, 70%, 71%, 72%, 73%, 74%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more (compared to antigen binding by the second antibody in the absence of the first antibody). Therefore, the inhibition of the binding of a first antibody to an antigen by a second antibody of 50%, 605, 70%, 71%, 72%, 73%, 74%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more indicates that the two antibodies bind to the same epitope. The present invention encompasses variant antibodies, sometimes referred to as "antibody derivatives" or "antibody analogs" as well. That is, there are a number of modifications that can be made to the antibodies disclosed in the present i cci η / ηζηζ / Ε / γ, including, but not limited to, amino acid modifications in the CDRs (affinity maturation), amino acids in the framework regions, amino acid modifications in the Fe region, glycosylation variants, covalent modifications of other types (eg for adhesion of drug conjugates, etc.). By "variant" in this invention is meant a polypeptide sequence that differs from that of a parent polypeptide by virtue of at least one amino acid modification. In this case, the parent polypeptide is the full-length variable heavy or light chains, for example, as listed in SEQ ID NOs: 1 or 2, respectively, or the CDR regions or heavy and light chain framework regions listed in SEQ ID NOs 5-10 and 16-21 for LY75. Amino acid modifications can include substitutions, insertions, and deletions, with the former being preferred in many cases. It will be understood that an amino acid substitution may be a conservative or non-conservative substitution with conservative substitutions being preferred. Additionally said substitution may be a substitution with either a naturally occurring or non-naturally occurring amino acid. In general, variants can include any number of modifications, as long as the antibody function is still present, as described herein. That is, LY75_A1, for example, the antibody should still specifically bind to human LY75. If the amino acid variants with the Fc region are generated, for example, the variant antibodies should maintain the receptor-binding functions required for the particular application or indication of the antibody. "Variants" in this case can be made from the listed CDR sequences, framework or Fe regions of the antibody. However, in general, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions are generally used as the goal is often to alter function with a minimal amount of modification. In some cases, between 1 and 5 modifications (eg, individual amino acid substitutions, insertions or deletions) exist, with between 1-2, 1-3 and 1-4 being useful in many embodiments as well. The number of modifications may depend on the size of the region being modified; for example, in general, minor amounts of modifications in CDR regions are desired. One skilled in the art will understand that even within CDR regions the location of the modification can significantly alter the effect. In one embodiment, the modifications can be made in any of CDR1, CDR2 or CDR3 of the heavy and / or light chains. In a further embodiment, the modifications are made in either CDR1 or CDR2 of the heavy and / or light chains. In yet another embodiment, the modifications are located in CDR1 of the heavy and / or light chains. It should be noted that the number of amino acid modifications may be i cci η / ηζηζ / Ε / γ within functional domains: for example, it may be desirable to have between 1-5 modifications in the Fe region of wild-type or engineered proteins , as well as between 1 and 5 modifications in the Fv region, for example. A variant polypeptide sequence will preferably possess at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the similar sequences (eg, the variable regions, the constant regions, and / or the heavy and light chain sequences and / or the CDRs of LY75_A1). It should be noted that depending on the size of the sequence, the percent identity will depend on the number of amino acids. By "amino acid substitution" or "substitution" in this invention is meant the replacement of an amino acid at a particular position in a precursor polypeptide sequence with another amino acid which may be a natural or non-naturally occurring amino acid. For example, the S100A substitution refers to a variant polypeptide in which the serine at position 100 is replaced with alanine. By "amino acid insertion" or "insertion" in the present context is meant the addition of an amino acid at a particular position in a precursor polypeptide sequence. By "amino acid deletion" or "deletion" in the present context is meant the removal of an amino acid at a particular position in a precursor polypeptide sequence. By "parent polypeptide," "parent protein," "parent polypeptide," or "precursor protein" in the present context is meant an unmodified polypeptide that is subsequently modified to generate a variant. In general, the precursor polypeptide in this invention is LY75_A1. Accordingly, by "parent antibody" in the present context is meant an antibody that is modified to generate a variant antibody. By "wild type" or "WT" or "native" in this invention is meant an amino acid sequence or a nucleotide sequence that is found in nature, including allelic variations. A WT protein, polypeptide, antibody, immunoglobulin, IgG, etc. has an amino acid sequence or a nucleotide sequence that has not been intentionally modified. By "variant Fe region" in this invention is meant an Fe sequence that differs from that of a wild-type Fe sequence by virtue of at least one amino acid modification. Variant Fe can refer to the Fe polypeptide itself, to compositions comprising the variant Fe polypeptide, or to the amino acid sequence. In some embodiments, one or more amino acid modifications are made to one or more of the CDRs of LY75_A1. In general, only 1 or 2 or 3 amino acids are substituted in any single CDR, and generally no more than 4, 5, 6, 7, 8, 9 or 10 changes are made within a set of 6 CDRs. However, it should be appreciated that i ccc i n / nznz / E / YiAi any combination of non-substitutions, 1, 2 or 3 substitutions in any CDR can be independently and optionally combined with any other substitution. It will be apparent that substitutions can be made in any of the 6 CDRs. In one embodiment, the substitutions are made in CDR1 of the heavy and / or light chains. In some cases, amino acid modifications in CDRs are referred to as "affinity maturation." An "affinity matured" antibody is one that has one or more alterations in one or more CDRs which results in an improvement in the affinity of the antibody for the antigen, compared to a parent antibody which does not possess those alterations. In some cases, although rare, it may be desirable to reduce the affinity of an antibody for its antigen, but this case is not generally preferred. Affinity maturation can be performed to increase the binding affinity of the antibody for the antigen by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 100%, about 110%, about 120%, about 130%, about 140%, about 150% or more, or 1,2, 3, 4 up to 5 times as compared to the antibody" precursor". Preferred affinity matured antibodies will have nanomolar or even picomolar affinities for the target antigen. Affinity matured antibodies are produced by known procedures. See, for example, Marks et al., 1992, Biotechnology 10:779-783 which describes affinity maturation by variable heavy (VH) and variable light (VL) chain domain shuffling. Random mutagenesis of CDRs and / or framework residues is described in: Barbas, et al. 1994, Proc. Nat. Acad. Seoul, U.S.A. 91:3809-3813; Shier et al., 1995, Gene 169:147-155; Yelton et al., 1995, J. Immunol. 155:1994-2004; Jackson et al., 1995, J. Immunol. 154(7):3310-9; and Hawkins et al., 1992, J. Mol. Biol. 226:889-896, for example. Alternatively, amino acid modifications can be made to one or more of the CDRs of the antibodies of the invention that are "silent", eg, that do not significantly alter the affinity of the antibody for the antigen. These can be done for a number of reasons, including optimization of expression (as can be done for nucleic acids encoding the antibodies of the invention). Thus, included within the definition of CDRs and antibodies disclosed herein are variant CDRs and antibodies; that is, the antibodies may include amino acid modifications in one or more of the LY75 A1 CDRs. In addition, as discussed below, amino acid modifications can also be independently and optionally made in any region outside of the CDRs, including framework and constant regions as described herein. In some embodiments, the anti-LY75 antibodies disclosed herein are i cci η / ηζηζ / Ε / γ composed of a variant Fe domain. As is known in the art, the Fe region of an antibody interacts with a number of Fe receptors and ligands, imparting a variety of important functional capabilities termed effector functions. These Fc receptors include, but are not limited to, (in humans) FcyRI (CD64) including the isoforms FcyRIa, FcyRIb, and FcyRIc; FcyRII (CD32), including the isoforms FcyRIIa (including the H131 and R131 allotypes), FcyRIIb (including FcyRllb-1 and FcyRllb-2), and FcyRIIc; and FcyRIII (CD16), including the isoforms FcyRIIIa (including the V158 and F158 allotypes, correlated with antibody-dependent cellular cytotoxicity (ADCC)) and FcyRIIIb (including the FcyRlllb-NA1 and FcyRlllb-NA2 allotypes), FcRn (the receptor neonatal), C1q (the complementary protein involved in complement-dependent cytotoxicity (CDC)) and FcRn (the neonatal receptor involved in serum half-life). Suitable modifications can be made in one or more positions as generally disclosed, for example in US Patent Application 11 / 841,654 and in the references cited therein, US 2004 / 013210, US 2005 / 0054832, US 2006 / 0024298, US 2006 / 0121032, US 2006 / 0235208, US 2007 / 0148170, USSN 12 / 341,769, US Patent No. 6,737,056, US Patent No. 7,670,600, US Patent No. 6,086,875 all of these documents are expressly incorporated by reference in their entirety , and in particular for specific amino acid substitutions that increase binding to Fe receptors. In addition to the modifications set forth above, other modifications may be made. For example, molecules can be stabilized by incorporating disulfide bridges that link the VH and VL domains (Reiter et al., 1996, Nature Biotech. 14:1239-1245, incorporated by reference in its entirety). In addition, cisternae modifications are particularly useful in antibody-drug conjugate (ADC) applications, described further below. In some embodiments, the constant region of antibodies can be engineered to contain one or more cisternae that are particularly "thiol reactive" so as to allow more specific and controlled placement of the drug moiety. See, for example, US Patent No. 7,521,541, incorporated by reference in its entirety herein. Additionally, there are a variety of covalent modifications of antibodies that can be performed as discussed below. Covalent modifications of antibodies are included within the scope of this invention, and are generally, though not always, performed in a post-translational manner. For example, various types of covalent modifications of the antibody are introduced into the molecule by reacting specific amino acid residues of the antibody with an organic derivatizing agent that is capable of reacting with selected i ccci η / ηζηζ / Ε / γ side chains or residues. of terminal N or C. Cysteinyl residues are most commonly reacted with α-haloacetates (and corresponding amines), such as chloroacetic acid or chloroacetamide, to give carboxymethyl or carboxyamidomethyl derivatives. Cysteinyl residues can also be derivatized by reaction with bromotrifluoroacetone, a-bromo-p-(5-imidozoyl)proponic acid, chloroacetyl phosphate, N-alkylmaleimides, 3-nitro-2-pyridyl disulfide, 2- methyl pyridyl disulfide, p-chloromercuribenzoate, 2-chloromercuri-4-nitrophenol, or chloro-7-nitrobenzo-2-oxa1,3-diazole and the like. Histidyl residues are derived by reaction with diethylpyrocarbonate at pH 5.5-7.0 since this agent is relatively specific for the histidyl side chain. Para-bromophenacyl bromide is also useful; the reaction is preferably carried out in 0.1 M sodium cacodylate at pH 6.0. Terminal lysinyl and amino residues are reacted with anhydrides of succinic acid and other carboxylic acids. Derivatization with these agents has the effect of reversing the charge of lysinyl residues. Other suitable reagents for derivatizing alpha-amino-containing residues include imidoesters such as methyl picolinimidate; pyridoxal phosphate; pyridoxal; chloroborohydride; trinitrobenzenesulfonic acid; O-methylisourea; 2,4pentandione; and transaminase-catalyzed reaction with glyoxylate. Arginyl residues are modified by reaction with one or more conventional reagents, including phenylglyoxal, 2,3-butandione, 1,2-cyclohexandione, and ninhydrin. The derivatization of arginine residues requires that the reaction be carried out under alkaline conditions due to the high pKa of the guanidine functional group. Additionally, these reagents can react with the lysine groups as well as the epsilonamino group of arginine. Specific modification of tyrosyl residues can be effected, with particular interest in the introduction of spectral labels into tyrosyl residues by reaction with aromatic diazonium compounds or tetranitromethane. More commonly, N-acetylimidizole and tetranitromethane are used to form O-acetyl tyrosyl species and 3-nitro derivatives, respectively. Tyrosyl residues are iodinated using 1251 or 1311 to prepare labeled proteins for use in radioimmunoassay, the chloramine T method described above being suitable. Carboxyl side groups (aspartyl or glutamyl) are selectively modified by reaction with carbodiimides (R'—N=C=N—R'), where R and R' are optionally different alkyl groups, such as 1 —cyclohexyl—3—( 2-morpholinyl-4-ethyl)carbodiimide or 1-ethyl-3-(4-azona-4,4-dimethylpentyl)carbodiimide. Additionally, aspartyl and glutamyl residues are converted to asparaginyl and glutaminyl residues by reaction with ammonium ions. i ccci η / ηζηζ / Ε / γ Derivatization with bifunctional agents is useful for cross-linking antibodies to a water-insoluble matrix or support surface for use in a variety of methods, in addition to the methods described below. Commonly used crosslinking agents include, for example, 1,1-bis(diazoacetyl)-2-phenylethane, glutaraldehyde, N-hydroxysuccinimide esters, for example, esters with 4-azidosalicylic acid, homobifunctional imidoesters, including disuccinimidyl esters such as 3, 3'-dithiobis(succinimidylpropionate), and bifunctional maleimides such as bis-N-maleimido-1,8-octane. Derivatizing agents such as methyl-3-[(pazidophenyl)dithio]propiodate provide photoactivatable intermediates that are capable of forming crosslinks in the presence of light. Alternatively, reactive water-insoluble matrices such as cyanogen bromide-activated carbohydrates and reactive substrates described in US Pat. Nos. 3,969,287; 3,691,016; 4,195,128; 4,247,642; 4,229,537; and 4,330,440, all incorporated in their entirety by reference, are used for protein immobilization. Glutaminyl and asparaginyl residues are frequently deamidated to the corresponding glutamyl and aspartyl residues, respectively. Alternatively, these residues are deamidated under mildly acidic conditions. Any form of these residues falls within the scope of this invention. Other modifications include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of the α-amino groups of lysine, arginine, and histidine side chains (T. E. Creighton, Proteins: Structure and Molecular Properties, W. H. Freeman & Co., San Francisco, pp. 79-86

[1983] , incorporated in their entirety by reference), acetylation of the N-terminal amine, and amidation of any C-terminal carboxyl groups. Furthermore, as will be appreciated by those skilled in the art, labels (including fluorescent, enzymatic, magnetic, radioactive, etc.) can all be added to antibodies (as can the other compositions of the invention). Another type of covalent modification is alterations in glycosylation. In some embodiments, the antibodies described in this invention may be fully or partially aglycosylated, eg, afucosylated. Another type of covalent modification of the antibody involves ligation of the antibody to various non-proteinaceous polymers, including, but not limited to, various polyols such as polyethylene glycol, polypropylene glycol, or polyoxyalkylenes, as set forth in, for example, the 2005-2006 PEG Nektar Catalog. Therapeutics (available on the Nektar website) US Patents Ne4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192 or 4,179,337, all incorporated in their entirety by reference. In addition, as is known in the art, amino acid substitutions can be made at various positions within the antibody to facilitate the addition of polymers such as PEG. See, for example, United States of America Publication No. 2005 / 0114037A1, incorporated by reference in its entirety. In additional embodiments, the antibodies may comprise a tag. By "labeling" in this invention is meant that a compound has at least one element, isotope, or chemical compound attached to it to allow detection of the compound. In general, labels fall into three classes: a) isotopic labels, which can be radioactive or heavy isotopes; b) magnetic, electrical, thermal; and c) colored or luminescent dyes; although the tags include enzymes and particles such as magnetic particles as well. Preferred labels include, but are not limited to, fluorescent lanthanide complexes (including those of Europium and Terbium), and fluorescent labels including, but not limited to, quantum dots, fluorescein, rhodamine, tetramethylrhodamine, eosin, erythrosine, coumarin, methyl- Coumarins, Pyrene, Malacite Green, Stilbene, Lucifer Yellow, Cascade Blue, Texas Red, Alexa Dyes, Cy Dyes, and others described in the Molecular Probes Handbook, Sixth Edition by Richard P. Haugland, expressly incorporated herein by way of reference. Antibody-Drug Conjugates In some embodiments, the anti-LY75 antibodies disclosed herein are conjugated with drugs to form antibody-drug conjugates (ADCs). In general, ADCs are used in oncology applications, where the use of antibody-drug conjugates for local delivery of cytotoxic and cytostatic agents allows targeted delivery of the drug moiety to tumors, which may allow for greater efficacy, less toxicity etc A review of this technology is provided in Ducry et al., Bioconjugate Chem., 21:5-13 (2010), Carter et al., Cancer J. 14(3):154 (2008) and Senter, Current Opin. Chem. Bio!. 13:235-244 (2009), all of which are incorporated herein by reference in their entirety. Thus the invention provides pharmaceutical combinations comprising, inter alia, drug-conjugated anti-LY75 antibodies. In general, conjugation is accomplished by covalent attachment to the antibody, as described further below, and generally relies on a linker, often a peptide ligation (which, as described below, can be designed to be sensitive to cleavage by proteases at the target site or not). Additionally, as described above, ligation of the linker-drug junction (LU-D) can be accomplished by binding to cisternae within the antibody. As will be appreciated by those skilled in the art, the amount of drug moieties per antibody can change, depending on reaction conditions, and can range from 1:1 to 10:1 drug:antibody. As will be appreciated by those skilled in the art, the actual amount is an average. i ccci η / ηζηζ / Ε / γ Thus, anti-LY75 antibodies can be conjugated to drugs. As described below, the ADC drug can be any number of agents, including but not limited to cytotoxic agents such as chemotherapeutic agents, growth inhibitory agents, toxins (eg, an enzymatically active toxin of bacterial, fungal, plant or animal, or fragments thereof), or a radioactive isotope (ie, a radioconjugate) are provided. In other embodiments, the invention further provides methods for using the ADCs. Drugs for use in the present invention include cytotoxic drugs, particularly those used for anticancer therapy. Such drugs include, in general, DNA damaging agents, anti-metabolites, natural products and their analogues. Exemplary classes of cytotoxic agents include enzyme inhibitors such as dihydrofolate reductase inhibitors, and thymidylate synthase inhibitors, DNA intercalators, DNA dissociators, topoisomerase inhibitors, the anthracycline family of drugs, the vinca drugs , mitomycins, bleomycins, cytotoxic nucleosides, the pteridine family of drugs, diinenes, podophyllotoxins, dolastatins, maytansinoids, differentiation inducers, and taxols. Members of these classes include, for example, taxol, methotrexate, metopterin, dichloromethotrexate, 5-fluorouracil, 6-mercaptopurine, cytosine arabinoside, melphalan, leurosine, leurosidein, actinomycin, daunorubicin, doxorubicin, mitomycin C, mitomycin A, caminomycin, aminopterin , thalisomycin, podophyllotoxin and podophyllotoxin derivatives such as etoposide or etoposide phosphate, vinblastine, vincristine, vindesine, taxanes including taxol, taxotere retinoic acid, butyric acid, N8-acetyl spermidine, camptothecin, calicheamicin, esperamicin, eno-diynes, duocarmycin A, duocarmycin SA, calicheamicin, camptothecin, hemiasterlins, maytansinoids (including DM1), monomethylauristatin E (MMAE), monomethylauristatin F (MMAF), and maytansinoids (DM4) and their analogs. Toxins can be used as antibody-toxin conjugates and include bacterial toxins such as diphtheria toxin, plant toxins such as ricin, small molecule toxins such as geldanamycin (Mandler et al (2000) J. Nat. Cancer Inst. 92(19 Letters 10:1025-1028; Mandler et al (2002) Bioconjugate Chem. 13:786-791), maytansinoids (EP 1391213; Liu et al., (1996) Proc. Nati. Acad. Sel. USA 93:8618-8623), and calicheamicin (Lode et al (1998) Cancer Res. 58:2928; Hinman et al (1993) Cancer Res. 53:3336-3342) , hemiasterlins (WO2004 / 026293; Zask et al., (2004) J. Med. Chem, 4774-4786). Toxins can exert their cytotoxic and cytostatic effects by mechanisms including tubulin binding, DNA binding, or topoisomerase inhibition. Conjugates of an anti-LY75 antibody and one or more small molecule toxins, such as maytansinoids, dolastatins, auristatins, a trichothecene, calicheamicin, iccci n / nznz / E / v duocarmycins, pyrrolobenzodiazepines, and CC1065, and derivatives thereof toxins having toxin activity may also be used. Preferably, the anti-LY75 antibody is conjugated to DM1 or DM4, more preferably DM4. Maytansine compounds suitable for use as maytansinoid drug moieties are well known in the art, and can be isolated from natural sources according to known methods, produced using genetic engineering techniques (see Yu et al (2002) PNAS 99:7968- 7973), or maytansinol and maytansinol analogues prepared synthetically according to known methods. As described below, drugs can be modified by incorporating a functionally active group such as a thiol or amine group for conjugation to the antibody. Exemplary maytansinoid drug moieties include those having a modified aromatic ring, such as: C-19-dechloro (US Patent No. 4,256,746) (prepared by lithium aluminum hydride reduction of ansamitocin P2); C-20hydroxy (or C-20-demethyl) + / -C-19-dechloro (US Patent Nos. 4,361,650 and 4,307,016) (prepared by demethylation using Streptomyces or Actinomyces or dechlorination using LAH); and C-20-demethoxy, C-20-acyloxy (—OCOR), + / -dechloro (US Patent No. 4,294,757) (prepared by acylation using acyl chlorides), and those having modifications at other positions. Exemplary maytansinoid drug moieties further include those having modifications such as: C-9-SH (US Patent No. 4,424,219) (prepared by the reaction of maytansinol with H2S or P2S5); C-14alkoxymethyl(demethox¡ / CH2OR) (US Patent No. 4,331,598); C-14-hydroxymethyl or acyloxymethyl (CH2OH or CH2OAc) (US Patent No. 4,450,254) (prepared from Nocardia); C-15-hydroxy / acyloxy (US Patent No. 4,364,866) (prepared by the conversion of maytansinol by Streptomyces); C-15-methoxy (US Patent Nos. 4,313,946 and 4,315,929) (isolated from Trewia nudlflora); C-18-N-demethyl (US Patent Nos. 4,362,663 and 4,322,348) (prepared by the demethylation of maytansinol by Streptomyces); and 4,5-deoxy (US Patent No. 4,371,533) (prepared by titanium trichloride / LAH reduction of maytansinol). Of particular use are DM1 (described in US Patent No. 5,208,020, incorporated by reference) and DM4 (described in US Patent No. 7,276,497, incorporated by reference). Also see a number of additional maytansinoid derivatives and methods at 5,416,064, WO / 01 / 24763, 7,303,749, 7,601,354, USSN 12 / 631,508, WO02 / 098883, 6,441,163, 7,368,565, WO02 / 16368 and WO02 / 09888, all of which are expressly incorporated20. for reference in its entirety. Maytansinoid-containing ADCs, methods for their preparation, and their therapeutic use are described, for example, in US Pat. Nos. 5,208,020; 5,416,064; 6,441,163 and in European Patent EP 0 425 235 B1, the descriptions of which are expressly incorporated herein by reference. Liu et al., Proc. nati. Acad. Sci. USA 93:8618-8623 (1996) described ADCs comprising a maytansinoid designated DM1 linked to the C242 monoclonal antibody directed against human colorectal cancer. The conjugate was found to be highly cytotoxic towards cultured colon cancer cells, and showed antitumor activity in an in vivo tumor growth assay. Chari et al., Cancer Research 52:127-131 (1992) describe ADCs in which a maytansinoid was conjugated via a disulfide linker to the murine A7 antibody that binds an antigen in human colon cancer cell lines, or to another murine monoclonal antibody TA.1 that binds to the HER-2 / neu oncogene. The cytotoxicity of the TA.I-maytansinoid conjugate was tested in vitro in the human breast cancer cell line SKBR-3, which expresses 3x10 5 HER-2 surface antigens per cell. The drug conjugate achieved a degree of cytotoxicity similar to the free maytansinoid drug, which could be increased by increasing the number of maytansinoid molecules per antibody molecule. The A7-maytansin¡de conjugate showed low systemic cytotoxicity in mice. For compositions comprising a plurality of antibodies, the drug load is represented by p, the average number of drug molecules per Antibody. The pharmacological load can range from 1 to 20 drugs (D) per Antibody. The average amount of drugs per antibody in the preparation of the conjugation reactions can be characterized by conventional means such as mass spectroscopy, ELISA assay, and HPLC. The quantitative distribution of Antibody-Drug Conjugates in terms of p can also be determined. In some cases, the separation, purification and characterization of homogeneous Antibody-Drug Conjugates where p is a certain value of Antibody-Drug Conjugates with other drug loads can be accomplished by means such as reverse phase HPLC or electrophoresis. In exemplary embodiments, p is 2, 3, 4, 5, 6, 7, or 8 or a fraction thereof. The generation of antibody-drug conjugate compounds can be accomplished by any technique known to the skilled person. Briefly, the antibody-drug conjugate compounds can include an anti-LY75 antibody as the antibody unit, a drug, and optionally a linker that binds the drug and binding agent. A number of different reactions are available for the covalent attachment of drugs and / or linkers to binding agents. This can be achieved by reaction of the amino acid residues of the binding agent, eg, antibody molecule, including the amine groups of lysine, the free carboxylic acid groups of i cci η / ηζηζ / Ε / γ glutamic and aspartic acid, the cysteine ​​sulfhydryl groups and the various portions of the aromatic amino acids. A commonly employed non-specific method of covalent linkage is the carbodiimide reaction to link a carboxy (or amino) group of a compound to amino (or carboxy) groups of the antibody. Additionally, bifunctional agents such as dialdehydes or imidoesters have been used to link the amino group of a compound to amino groups of an antibody molecule. Also available for binding of drugs to binding agents is the Schiff base reaction. This method involves the periodate oxidation of a drug containing glycol or hydroxy groups, thereby forming an aldehyde which is then reacted with the binding agent. The binding occurs through the formation of a Schiff base with amino groups of the binding agent. Isothiocyanates can also be used as coupling agents to covalently bind drugs to binding agents. Other techniques are known to the person skilled in the art and are within the scope of the present invention. In some embodiments, an intermediate, which is the precursor of the linker, is reacted with the drug under appropriate conditions. In other embodiments, reactive groups are used on the drug and / or intermediate. The product of the reaction between the drug and the intermediate, or the derivative drug, is subsequently reacted with an anti-LY75 antibody of the invention under appropriate conditions. It will be understood that chemical modifications may also be made to the desired compound in order to make reactions of that compound more convenient for the purposes of preparing conjugates of the invention. For example a functional group eg amine, hydroxyl, or sulfhydryl, may be attached to the drug in one portion which has little or acceptable effect on the activity or other properties of the drug. In general, antibody-drug conjugate compounds comprise a linker unit between the drug unit and the antibody unit. In some embodiments, the linker is cleavable under intracellular or extracellular conditions, such that dissociation of the linker releases the drug unit from the antibody into the appropriate environment. For example, solid tumors that secrete certain proteases can serve as the target of the cleavable linker; in other embodiments, intracellular proteases are used. In still other embodiments, the linker unit is not dissociable and the drug is released, for example, by degradation of antibodies in lysosomes. In some embodiments, the linker is cleavable by a cleavage agent that is present in the intracellular environment (eg, within a lysosome or endosome or caveolae). The linker can be, for example, a peptidyl linker that is cleaved by an intracellular peptidase or protease enzyme, including, but not limited to, a lysosomal or endosomal protease. In some embodiments, the peptidyl iccci n / nznz / E / v linker is at least two amino acids long or at least three amino acids long or more. Dissociation agents may include, but are not limited to, cathepsins B and D and plasmin, all of which are known to hydrolyze dipeptide drug derivatives resulting in the release of the active drug into target cells (see, for example, Dubowchik and Walker, 1999, Pharm Therapeutics 83:67-123). Peptidyl linkers can be cleaved by enzymes that are present in cells expressing LY75. For example, a peptidyl linker that is cleavable by the thiol-dependent protease cathepsin-B, which is highly expressed in cancer tissue (for example, a Phe-Leu or a Gly-Phe-Leu-Gly linker (SEQ ID NOT: 46)). Other examples of such linkers are described, for example, in US Patent No. 6,214,345, incorporated herein by reference in its entirety and for all purposes. In some embodiments, the peptidyl linker cleavable by an intracellular protease is a Val—Cit linker or a Phe-Lys linker (see, for example, US Patent No. 6,214,345, which describes the synthesis of doxorubicin with the val-cit linker ). In other embodiments, the cleavable linker is pH sensitive, ie, it is sensitive to hydrolysis at certain pH values. In general, the pH sensitive linker is hydrolyzable under acidic conditions. For example, an acid labile linker that is hydrolyzable in the lysosome can be used (eg, a hydrazone, semicarbazone, thiosemicarbazone, cisaconitic amide, orthoester, acetal, ketal, or the like). (See, for example, US Patent Nos. 5,122,368; 5,824,805; 5,622,929; Dubowchik and Walker, 1999, Pharm. Therapeutics 83:67-123; Neville et al., 1989, Biol. Chem. 264:14653-14661.) Such linkers are relatively stable under neutral pH conditions, such as those in blood, but are unstable below pH 5.5 or 5.0, the approximate pH of the lysosome. In certain embodiments, the hydrolyzable linker is a thioether linker (such as, for example, a thioether attached to the therapeutic agent via an acylhydrazone bond (see, for example, US Patent No. 5,622,929). In still other embodiments, the linker is cleavable under reducing conditions (eg, a disulfide linker). Various disulfide linkers are known in the art, including, for example, those that can be formed using SATA (N-succinimidyl-5-acetylthioacetate), SPDP (N-succinimidyl-3-(2-pyridyldithio)propionate), SPDB (N- succinimidyl-3(2-pyridyldithio)butyrate) and SMPT (N-succinimidyl-oxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio)toluene)-, SPDB and SMPT. (See, for example, Thorpe et al., 1987, Cancer Res. 47:5924-5931; Wawrzynczak et al., In Immunoconjugates: Antibody Conjugales in Radioimaging and Therapy of Cancer (C. W. Vogel ed., Oxford U. Press, 1987 See also US Patent No. 4,880,935). In other embodiments, the linker is a malonate linker (Johnson et al., 1995, i cci η / ηζηζ / Ε / γ Anticancer Res. 15:1387-93), a maleimidobenzoyl linker (Lau et al., 1995, Bioorg-MedChem. 3(10):1299-1304), or a 3'-N-amide analog (Lau et al ., 1995, Bioorg-Med-Chem. 3(10):1305-12). In still other embodiments, the linker unit is not dissociable and the drug is released by degradation of antibodies. (See US Publication No. 2005 / 0238649 incorporated by reference herein in its entirety and for all purposes). In many embodiments, the ligator is self-destructive. In the present context, the term "self-destructive spacer" refers to a bifunctional chemical moiety that is capable of covalently linking two spaced apart chemical moieties together in a stable tripartite molecule. It will spontaneously separate from the second chemical moiety if its bond to the first moiety is dissociated. See for example, WO 2007 / 059404A2, WO06 / 110476A2, WO05 / 112919A2, WO2010 / 062171, WO09 / 017394, WO07 / 089149, WO 07 / 018431, WO04 / 043493 and WO02 / 083180, with said drug jugates referring to - cleavable substrate where the drug and the cleavable substrate are optionally linked through a self-destructive linker and said documents are expressly incorporated by reference. Often the linker is not substantially sensitive to the extracellular environment. In the present context, "substantially not sensitive to the extracellular environment," in the context of a linker, means that no more than about 20%, 15%, 10%, 5%, 3%, or no more than about 1% of The linkers, in a sample of antibody-drug conjugate, dissociate when the antibody-drug conjugate is present in an extracellular environment (eg, plasma). Whether a linker is substantially insensitive to the extracellular environment can be determined, for example, by incubating the antibody-drug conjugate with plasma for a predetermined period of time (for example, 2, 4, 8, 16, or 24 hours) and then measuring the amount of free drug present in the plasma. In other, non-mutually exclusive embodiments, the linker promotes cell internalization. In certain embodiments, the linker promotes cellular internalization when conjugated to the therapeutic agent (ie, in the vicinity of the linker-therapeutic agent portion of the antibody-drug conjugate as described herein). In yet other embodiments, the linker promotes cell internalization when conjugated to both the auristatin compound and the anti-LY75 antibodies of the invention. A variety of exemplary linkers that can be used with the present compositions and methods are described in WO 2004 / 010957, US Publication No. 2006 / 0074008, US Publication No. 20050238649, and US Publication No. 2006 / 0024317 (each of which is incorporated by reference herein in its entirety and for all purposes). Preferably, the linker is SPDB (N-succ¡n¡m¡d¡l-3-(2-p¡r¡d¡ldit¡o)but¡rato). Drug loading is represented by p and is the average number of drug moieties for each antibody in a molecule. The drug loading ("p") can be 1,2,3, 4, 5, 6, 7, 8, 9,10,11,12,13, 14, 15, 16, 17, 18, 19, 20 or more portions (D) for each antibody, although often the average number is a fraction or decimal. In general, drug loading is 1 to 4 is often helpful, and 1 to 2 is also useful. The ADCs of the invention include pools of antibody conjugates with a range of drug moieties, between 1 and 20, eg, 1-15, 1-10, 2-9, 3-8, 4-7, 5-6 . The average number of drug moieties per antibody in ADC preparations from conjugation reactions can be characterized by conventional means such as mass spectroscopy and ELISA assay. The quantitative distribution of ADC in terms of p can also be determined. In some cases, the separation, purification and characterization of homogeneous DNA where p is a certain ADC value with other drug loads can be accomplished by means such as electrophoresis. For some antibody-drug conjugates, p may be limited by the number of binding sites on the antibody. For example, where the linkage is a cysteine ​​thiol, as in the above exemplary embodiments, an antibody may have only one or more cysteine ​​thiol groups, or may have only one or more sufficiently reactive thiol groups through which it can bind. a binder. In certain embodiments, a higher drug loading, eg p>5, can cause aggregation, insolubility, toxicity, or loss of cell permeability of certain antibody-drug conjugates. In certain embodiments, the drug loading for an ADC of the invention ranges from 1 to about 8; between about 2 and about 6; between about 3 and about 5; between about 3 and about 4; between about 3.1 and about 3.9; between about 3.2 and about 3.8; between about 3.2 and about 3.7; between about 3.2 and about 3.6; between about 3.3 and about 3.8; or between about 3.3 and about 3.7. In fact, it has been shown that for certain ADCs, the optimal ratio of drug moieties to each antibody may be less than 8, and may be from about 2 to about 5. See US 2005 / 0238649 A1 (incorporated herein by way of reference in its entirety). In certain embodiments, less than the theoretical maximum of drug moieties are conjugated to an antibody during a conjugation reaction. An antibody may contain, for example, lysine residues that do not react with the drug-binding intermediate or binding reagent, as described below. In general, antibodies do not contain many free and reactive cysteine ​​thiol groups which can be linked to a drug moiety; in fact most cysteine ​​thiol residues in antibodies exist as disulfide bridges. In certain embodiments, an antibody can be reduced with a reducing agent such as dithiothreitol (DTT) or tricarbonylethylphosphine (TCEP), under partially or fully reducing conditions, to generate cysteine ​​thiol reactive groups. In certain embodiments, an antibody is subjected to denaturing conditions to reveal reactive nucleophilic groups such as lysine or cysteine. The charge (drug / antibody ratio) of an ADC can be controlled in different ways, for example: (i) limiting the molar excess of drug-linker intermediate or linker reagent relative to antibody, (ii) limiting the time or the temperature of the conjugation reaction, (iii) partially or (sic) limiting the reductive conditions for cysteine ​​thiol modification, (iv) modified by recombinant techniques the amino acid sequence of the antibody so that the number and position of the cysteine ​​residues are modified for control of the amount and / or position of linker-drug adhesions (such as thioMab or thioFab prepared as described in this invention and in WO2006 / 034488 (herein incorporated by reference at its entirety)). It will be understood that where more than one nucleophilic group reacts with a drug-linker intermediate or linker reagent followed by drug moiety reagent, then the resulting product is a mixture of ADC compounds with a distribution of one or more drug moieties bound to an antibody. The average number of drugs for each antibody can be calculated from the mixture using a dual ELISA antibody assay, which is antibody-specific and drug-specific. Individual ADC molecules can be identified in the mixture by mass spectroscopy and separated by HPLC, eg hydrophobic interaction chromatography. In some embodiments, a homogeneous ADC with a single charge value can be isolated from the conjugation mixture by electrophoresis or chromatography. Methods to determine the cytotoxic effect of ADCs Methods for determining whether a drug or Antibody-drug conjugate exerts a cytostatic and / or cytotoxic effect on a cell are known. In general, the cytotoxic or cytostatic activity of an antibody-drug conjugate can be measured by: exposing mammalian cells expressing a target protein of the Antibody-Drug conjugate to cell culture medium; culturing the cells for a period between about 6 hours and about 5 days; and measuring cell viability. Cell-based in vitro assays can be used to measure the viability (proliferation), cytotoxicity, and induction of apoptosis (caspase activation) of the antibody-drug conjugate. To determine whether an Antibody-Drug conjugate exerts a cytostatic effect, a thymidine incorporation assay can be used. For example, cancer cells expressing a target antigen at a density of 5,000 cells / well from a plate of i cci η / ηζηζ / Ε / γ wells can be cultured for a period of 72 hours and exposed to 0.5 pCi of 3H- thymidine during the final 8 hours of the 72 hour period. 3Hthymidine incorporation into the culture cells is measured in the presence and absence of the Antibody-Drug conjugate. To determine cytotoxicity, necrosis or apoptosis (programmed cell death) can be measured. Necrosis is generally accompanied by increased plasma membrane permeability; cell dilation, and rupture of the plasma membrane. Apoptosis is generally characterized by vacuolization (“blebbing”) of the membrane, condensation of the cytoplasm, and activation of endogenous endonucleases. Determination of any of these effects on cancer cells indicates that an Antibody-Drug conjugate is useful in the treatment of cancers. Cell viability can be measured by determining in a cell the uptake of a dye such as neutral red, trypan blue, or ALAMAR™ blue (see, for example, Page et al., 1993, Intl. J. Oncology 3:473-476). . In that type of assay, cells are incubated in medium containing the dye, cells are washed, and the remaining dye, which reflects cellular uptake of the dye, is measured spectrophotometrically. The protein-binding dye sulforhodamine B (SRB) can also be used to measure cytotoxicity (Skehan et al., 1990, J. Nati. Cancer Inst. 82:1107-12). Alternatively, a tetrazolium salt, such as MTT, is used in a quantitative colorimetric assay for mammalian cell survival and proliferation by detecting live, but not dead cells (see, for example, Mosmann, 1983, J. Immunol. Methods 65 :55-63). Apoptosis can be quantified by measuring, for example, DNA fragmentation. Commercial photometric methods for the quantitative in vitro determination of DNA fragmentation are available. Examples of such assays, including TUNEL (which detects the incorporation of labeled nucleotides into fragmented DNA) and ELISA-based assays, are described in Biochemica, 1999, no. 2, p. 3437 (Roche Molecular Biochemicals). Apoptosis can also be determined by measuring morphological changes in a cell. For example, as with necrosis, loss of plasma membrane integrity can be determined by measuring the uptake of certain dyes (eg, a fluorescent dye such as, for example, acridine orange or ethidium bromide). A method for measuring the number of apoptotic cells has been described by Duke and Cohen, Current Protocols in Immunology (Coligan et al. eds., 1992, pp. 3.17.1-3.17.16). Cells can also be labeled with a DNA stain (eg, acridine orange, ethidium bromide, or propidium iodide) and cells observed for chromatin condensation and margination along the inner nuclear membrane. Other morphological changes i cci η / ηζηζ / Β / γ that can be measured to determine apoptosis include, for example, cytoplasmic condensation, increased membrane vacuolization, and cell shrinkage. The presence of apoptotic cells can be measured in both the attached and "floating" compartments of the cultures. For example, both compartments can be collected by removing the supernatant, trypsinizing attached cells, pooling the preparations after a wash step by centrifugation (eg, 10 min at 2000 rpm), and detecting apoptosis (eg, measuring fragmentation). of DNA). (See, eg, Piazza et al., 1995, Cancer Research 55:3110-16). In vivo, the effect of an anti-LY75 antibody therapeutic composition of the invention can be evaluated in a suitable animal model. For example, xenogeneic models of cancer can be used, where explants of cancer or explanted xenograft tissues are introduced into immunocompromised animals, such as nude or SCID mice (Klein et ai., 1997, Nature Medicine 3: 402-408). Efficacy can be measured using assays that measure inhibition of tumor formation, tumor regression or metastasis, and the like. The therapeutic compositions employed in the practice of the aforementioned methods may be formulated into pharmaceutical compositions comprising a suitable carrier for the desired method of administration. Suitable carriers include any material that when combined with the therapeutic composition retains the antitumor function of the therapeutic composition and is generally non-reactive with the patient's immune system. Examples include, but are not limited to, any of a number of conventional pharmaceutical carriers such as sterile phosphate-buffered saline solutions, bacteriostatic water, and the like (see, generally, Remington's Pharmaceutical Sciences Issue No. 16, A. Osal., ed., 1980). Methods to produce antibodies The antibodies disclosed herein can be prepared by any suitable method. These methods include culturing a host cell that contains isolated nucleic acids encoding the antibodies. As those skilled in the art will appreciate, this can be done in a number of ways, depending on the nature of the antibody. In the case where the antibodies are traditional full-length antibodies, for example, a heavy chain variable region and a light chain variable region under such conditions that an antibody is produced and can be isolated. The variable heavy and light chains of LY75_A1 are described in this invention (both protein and nucleic acid sequences); as will be appreciated in the art, this can be easily increased to produce full length heavy and light chains. That is, having provided the DNA fragments encoding VH and VK i cci η / ηζηζ / Ε / γ segments as set forth in the present invention, these DNA fragments can be further manipulated by conventional recombinant DNA techniques, for example, to converting the variable region genes to full length antibody chain genes, Fab fragment genes, or an scFv gene. In these manipulations, a DNA fragment encoding VK or VH is operatively linked to another DNA fragment encoding another protein, such as an antibody constant region or a flexible linker. The term "operably linked" as used in this context is intended to mean that the two DNA fragments are joined such that the amino acid sequences encoded by the two DNA fragments remain in frame. Isolated DNA encoding the VH region can be converted into a full-length heavy chain gene by operatively linking the VH-encoding DNA to another DNA molecule encoding heavy chain constant regions (CH1, CH2, and CH3). Sequences of murine heavy chain constant region genes are known in the art [see for example Kabat, E.A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, US Department of Health and Human Services, NIH Publication No. 91-3242] and DNA fragments spanning these regions can be obtained by standard POR amplification. The heavy chain constant region may be an IgG1, IgG2, IgG3, IgG4, IgA, IgE, IgM or IgD constant region, but more preferably is an IgG1 or IgG4 constant region. For a Fab fragment heavy chain gene, the DNA encoding VH may be operatively linked to another DNA molecule encoding only the heavy chain CH1 constant region. Isolated DNA encoding the VL / VK region can be converted into a full-length light chain gene (as well as a Fab light chain gene) by operatively ligating the VL-encoding DNA to another constant region-encoding DNA molecule. light chain, CL. Sequences of light chain wall constant regions genes are known in the art [see, for example, Kabat, E.A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, US Department of Health and Human Services, NIH Publication No. 91-3242] and DNA fragments spanning these regions can be obtained by standard POR amplification. In preferred embodiments, the light chain constant region may be a kappa or lambda constant region. To create an scFv gene, the DNA fragments encoding VH and VL / VK are operably linked to another fragment encoding a flexible linker, for example encoding the amino acid sequence (Gly4-Ser)3, such that the VH and VL / VK sequences VK can be expressed as a contiguous single chain protein, with the VL / VK and VH regions attached by the flexible linker [see for example Bird et al. (1988) Science 242:423-426; Huston et al. (1988) Proc. nati. Acad. Sel. USA 85:5879-5883; McCafferty et al., (1990) Nature 348:55246 554], Nucleic acids are provided which encode the antibodies disclosed herein. Said polynucleotides encode both the variable and constant regions of each of the heavy and light chains, although other combinations are also contemplated in accordance with the compositions described in this invention. Polynucleotides can be in the form of RNA or DNA. Polynucleotides in the form of DNA, cDNA, genomic DNA, nucleic acid analogs, and synthetic DNA are also usable. DNA can be double-stranded or single-stranded, and if it is single-stranded, it can be either the coding (sense) strand or the noncoding (antisense) strand. The coding sequence encoding the polypeptide may be identical to the coding sequence provided in this invention or may be a different coding sequence, which sequence, as a result of redundancy or degeneracy of the genetic code, encodes the same polypeptides as the DNA provided in this invention. In some embodiments, the nucleic acids encoding the antibodies disclosed herein are incorporated into expression vectors, which may be extrachromosomal or designed to integrate into the genome of the host cell into which it is introduced. Expression vectors may contain any number of appropriate regulatory sequences (including, but not limited to, transcriptional or translational control sequences, promoters, ribosomal binding sites, enhancers, origins of replication, etc.) or other components (selection genes). , etc.), these are all operatively linked as is well known in the art. In some cases two nucleic acids are used and each is placed in a different expression vector (for example the heavy chain in a first expression vector, the light chain in a second expression vector), or alternatively they can be placed in the same expression vector. Those skilled in the art will appreciate that the design of the expression vector(s), including the selection of regulatory sequences, may depend on factors such as the choice of host cell, the expression level of the desired protein, etc. In general, the nucleic acids and / or expression can be introduced into a suitable host cell to create a recombinant host cell using any method appropriate for the selected host cell (eg, transformation, transfection, electroporation, infection), such that the or the nucleic acid molecules are operatively linked to one or more expression control elements (eg, in a vector, in a construct created by processes in the cell, integrated into the genome of the host cell). The resulting recombinant host cell can be maintained under conditions suitable for expression (for example in the presence of an inducer, in a suitable non-human animal, in a suitable culture medium supplemented with appropriate salts, growth factors, antibiotics, nutritional supplements, etc. ), whereby i ccc i n / nznz / E / YiAi the encoded polypeptides are produced. In some cases, the heavy chains are produced in one cell and the light chain in another. Mammalian cell lines available as hosts for expression are known in the art and include many immortalized cell lines available from the American Typed Culture Collection (ATCC), Manassas, VA including but not limited to Chinese hamster ovary cells ( CHO), HEK 293 cells, NSO cells, HeLa cells, Baby Hamster Kidney (BHK) cells, Monkey Kidney (COS) cells, human hepatocellular carcinoma (eg, Hep G2), and a number of other cell lines. Non-mammalian cells including but not limited to bacterial, yeast, insect and plant cells can also be used to express recombinant antibodies. In some embodiments, the antibodies can be produced in transgenic animals such as cows or chickens. General methods for molecular biology, expression, purification, and selection of antibodies are well known, for example, see US Patent Nos. 4,816,567, 4,816,397, 6,331,415, and 7,923,221, as well as Antibody Engineering, edited by Kontermann & Dubel, Springer, Heidelberg, 2001 and 2010 Hayhurst & Georgiou, 2001, Curr Opin Chem Biol 5:683-689; Maynard & Georgiou, 2000, Annu Rev Biomed Eng 2:339-76; and Morrison, S. (1985) Science 229:1202. Component (B) of the pharmaceutical combination is Venetoclax, or a pharmaceutically acceptable salt thereof. Venetoclax is a small-molecule oral drug that blocks the anti-apoptotic B-cell lantern 2 (Bcl-2) protein, resulting in programmed cell death. It is indicated for chronic lymphocytic leukemia (CLL) in patients with a specific chromosomal abnormality (17p deletion). In 2015, the US Food and Drug Administration (FDA) granted Breakthrough Therapy designation to Venetoclax for subjects with CLL who have relapsed or been refractory to prior treatment and have the 17p deletion gene mutation. The structural formula of Venetoclax is given below: i ccci η / ηζηζ / Β / γ Cl Its IUPAC name is 4-(4-{[2-(4-Chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl]methyl}-1 p¡peraz¡n¡l)- N-({3-n¡tro-4-[(tetrahydro-2H-pyran-4-lmethyl)am¡no]fen¡l}sulfon¡l)-2-(1 H-pyrrolo[ 2,3b]pyridin-5-yloxy)benzamide. Venetoclax is sold under the trade names Venclexta® in the United States and Venclyxto® in Europe. Pharmaceutical Compositions The pharmaceutical combination of the invention is in the form of a combined preparation for simultaneous, separate or sequential use. Similarly, in the methods of the invention, components (A) and (B) of the pharmaceutical combination may be administered to a patient simultaneously, separately, or sequentially. The term "combined preparation" includes fixed combinations and non-fixed combinations. The term "fixed combination" means that the active ingredients (eg, components (A) and (B)) are in the form of a single entity or dose. In other words, the active ingredients are present in a single composition or formulation. The term "non-fixed combination" means that the active ingredients (eg, components (A) and (B)) are present in different entities or doses (eg, as separate compositions or formulations), eg, as a kit of parts. The independent components (A) and (B) (in their desired compositions or formulations) can then be administered separately or sequentially, at the same time interval or at different time intervals. When administration is sequential, the delay in administering the second component should not be such that the benefit of the effect arising from the use of the combination is lost. Thus, in one embodiment, sequential treatment involves administration of each component of the combination within an 11-day period. In another modality, this period is 10 days. In another modality, this period is 9 days. In another modality, this period is 8 days. In another modality, this period is 7 days. In another modality, this period is within 6 days. In another modality, this period is within 5 days. In another modality, this period is within 4 days. In another modality, this period is within 3 days. In another modality, this period is within 2 days. In another embodiment, this period is within 24 hours. In another modality this period is within 12 hours. Components (A) and (B) can be administered in any order, eg, component (A) first and then component (B); or component (B) first and then component (A). The ratio between the total amounts of component (A) and component (B) to be administered in the combined preparation may vary, for example, in order to meet the needs of a sub-population of patients to be treated or the needs of i ccci η / ηζηζ / Ε / γ a single patient with different needs that may be due to age, sex, body weight, etc. from the patients. Components (A) and (B), whether present in a single composition or in separate compositions, may be formulated independently with one or more pharmaceutically acceptable carriers. The pharmaceutical combinations of the invention may also include at least one other antitumor agent, or with an anti-inflammatory or immunosuppressive agent. Examples of therapeutic agents that can be used in combination therapy are described in more detail below in the section on uses of the antibodies disclosed herein. In the present context, "pharmaceutically acceptable carrier" includes any or all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption-delaying agents, and the like that are physiologically compatible. Preferably, the carrier is suitable for intravenous, intramuscular, subcutaneous, parenteral, spinal or epidermal administration (eg by injection or infusion). Depending on the route of administration, the active compound, ie the antibody, immunoconjugate, or bispecific molecule, may be coated in a material to protect the compound from the action of acids and other natural conditions that can inactivate the compound. Components (A) and / or (B) may be in the form of one or more pharmaceutically acceptable salts. A "pharmaceutically acceptable salt" refers to a salt that retains the desired biological activity of the parent compound and does not impart any unwanted toxicological effects [see, for example, Berge, S.M., et al. (1977) J. Pharm. 66:1-19]. Examples of such salts include acid addition salts and base addition salts. Acid addition salts include those derived from non-toxic inorganic acids such as hydrochloric, nitric, phosphoric, sulfuric, hydrobromic, hydroiodic, phosphorous and the like, as well as non-toxic organic acids such as mono- and dicarboxylic acids. aliphatics, phenyl-substituted alkanoic acids, hydroxy alkanoic acids, aromatic acids, aromatic aliphatic and sultanic acids, and the like. Base addition salts include those derived from alkaline earth metals, such as sodium, potassium, magnesium, calcium, and the like, as well as non-toxic organic amines, such as Ν,Ν'-dibenzylethylenediamine, N-methylglucamine, chloroprocaine, choline , diethanolamine, ethylenediamine, procaine and the like. A pharmaceutical combination of the invention or part thereof may also include a pharmaceutically acceptable antioxidant. Examples of pharmaceutically acceptable antioxidants include: (1) water-soluble antioxidants, such as ascorbic acid, cysteine ​​hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite, and the like; (2) oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole i ccc i η / ηζηζ / Ε / γίΛΐ (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, alpha-tocopherol, and the like; and (3) metal chelating agents, such as citric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like. Examples of suitable aqueous and non-aqueous carriers that may be employed in the pharmaceutical combinations of the invention include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils, such as olive oil, and injectable organic esters, such as ethyl oleate. Appropriate fluidity can be maintained, for example, by the use of coating materials, such as lecithin, by maintaining the required particle size in the case of dispersions, and by the use of surfactants. These combinations or parts thereof may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the presence of microorganisms can be ensured both by sterilization procedures, above, and by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents, such as sugars, sodium chloride, and the like in the compositions. Additionally, prolonged absorption of the injectable dosage form can be achieved by including agents which delay absorption such as aluminum monostearate and gelatin. Pharmaceutically acceptable carriers include sterile aqueous solutions or dispersions and sterile powders for extemporaneous preparation of sterile injectable solutions or dispersions. The use of such media and agents for pharmaceutically active substances is known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, its use in the pharmaceutical compositions of the invention is contemplated. Supplementary active compounds can also be incorporated into the compositions. Therapeutic compositions typically must be sterile and stable under the conditions of manufacture and storage. The composition can be formulated as a solution, microemulsion, liposome, or other ordered structure suitable for high drug concentration. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. Appropriate fluidity can be maintained, for example, by the use of a coating such as lecithin, by maintaining the required particle size in the case of a dispersion, and by the use of surfactants. In many cases, it will be preferable to include isotonic agents, for example, sugars, sugar alcohols such as mannitol, sorbitol, or sodium chloride in the composition. Prolonged absorption of injectable compositions can be achieved by including in the composition an iccc i n / nznz / E / YiAi agent that delays absorption, for example, monostearate salts and gelatin. Sterile injectable solutions can be prepared by incorporating the active compound in the required amount in an appropriate solvent with one or a combination of the ingredients listed above, as required, followed by sterile microfiltration. In general, dispersions are prepared by incorporating the active compound into a sterile vehicle containing a basic dispersion medium and the required other ingredients from those listed above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freeze drying (lyophilization) which provide a powder of the active ingredient plus any additional desired ingredients from a sterile pre-filtered solution of the same. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will vary depending on the subject being treated, and the particular mode of administration. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will generally be that amount of the composition which produces a therapeutic effect. In general, of 100 percent, this amount will range from about 0.01 percent to about 99 percent active ingredient, preferably from about 0.1 percent to about 70 percent, more preferably from about 1 percent to about 30 percent active ingredient. active ingredient in combination with a pharmaceutically acceptable carrier. Dosage regimens are adjusted to provide the optimal desired response (eg, synergistic combination, therapeutic response). For example, a single bolus may be administered, various divided doses may be administered over time, or the dose may be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. It is especially advantageous to formulate parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form in the present context refers to physically discrete units suitable as unit dosages for the subjects to be treated; each unit contains a predetermined amount of active compound that is calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and are directly dependent on (a) the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and (b) the inherent limitations of the technique of formation of that type of active compound for the treatment of sensitivity in individuals. For anti-LY75 antibody administration, the dosage ranges from about 0.0001 to 100 mg / kg, for example, 0.001 to 50mg / kg, 0.005 to 20mg / kg, 0.01 i cci η / ηζηζ / Ε / γ to 10mg / kg and more generally 0.01 to 5 mg / kg, of the body weight of the host. For example dosages may be 0.05 mg / kg body weight, 0.1 mg / kg body weight, 0.3 mg / kg body weight, 0.3 mg / kg body weight, 0.5 mg / kg body weight, 1 mg / kg body weight, 2 mg / kg body weight, 3 mg / kg body weight, 4 mg / kg body weight, 5 mg / kg body weight, 6 mg / kg body weight, 7 mg / kg body weight 8 mg / kg body weight, 9 mg / kg body weight, 10 mg / kg body weight, 12 mg / kg body weight, 15 mg / kg body weight, 20 mg / kg body weight, 25 mg / kg body weight, 30 mg / kg body weight, or within the range of 0.1-20 mg / kg, 0.5-15 mg / kg, 1-10 mg / kg, 2-8 mg / kg, 3 -7mg / kg, 4-6mg / kg. An exemplary treatment regimen encompasses administration once a day, once every 2 days, once a week, once every two weeks, once every three weeks, once every four weeks, once a month, once every 6 weeks, once every 3 months, or once every 3 to 6 months. Preferred dosage regimens for an anti-LY75 antibody of the invention include 1 mg / kg body weight or 3 mg / kg body weight by intravenous administration, the antibody being administered using one of the following dosage schedules: (i) every four weeks for six dosages, then every three months; (ii) every three weeks; (i¡¡) 3 mg / kg of body weight once followed by 1 mg / kg of body weight every three weeks. In some embodiments, the dose of anti-LY75 antibody (eg, LY75 DM4) is adjusted to obtain a plasma antibody concentration of 10 to 1500 nm or 18 to 1200 nM (eg, approximately 18.75, 37.5, 75, 150 , 300, 600 or 1200 nM). Preferably, the anti-LY75 antibody (eg LY75 DM4) is adjusted to achieve a plasma antibody concentration of 15 nM, 50 to 100 nM or 500-1200 nm. In some modalities, the dosage of Venetoclax (or a pharmaceutically acceptable salt thereof) is adjusted to obtain a plasma concentration of 0.5 to 500 nM or 0.64 to 400 nM (for example, approximately 0.64, 3.2, 16, 80, 400 or 2000nM). Preferably, Venetoclax (or a pharmaceutically acceptable salt thereof) is adjusted to obtain a plasma concentration of 0.5 nM to 20 nM, 20 to 50 nM, 50-100 nM or 100-500 nm. It can be administered orally. In some embodiments, the dose of Venetoclax (or a pharmaceutically acceptable salt thereof) is approximately 100 mg, 200 mg, 300 mg, 400 mg, or 500 mg. Venetoclax or a pharmaceutically acceptable salt thereof may be administered with one or more of cyclophosphamide, hydroxydaunorubicin, oncovlna, and predison or prednisolone (ie, CHOP therapy). Preferably, the combination of components (A) and (B) is a synergistic combination. One skilled in the art will understand that a synergistic combination is one where the effect of the combination is greater than the sum of the effects of the individual components. Synergy can be quantified using the ChouTalalay combination index (Cl) (see “Evaluation of combination chemotherapy: integration of nonlinear regression, i cci η / ηζηζ / Ε / γ curve shift, isobologram, and combination index analyses, Zhao L, et al Clin Cáncer Res. ", Chou TC, Motzer RJ, Tong Y, Bosl GJ., Nati J. Cancer Inst. (1994) Oct 19;86(20):1517-24). This combination index (Cl) method is based on the multidrug effect equation derived from the median effect principle of the law of mass action. It provides a quantitative definition of strong synergy (Cl < 0.3), synergy (Cl = 0.3-0.9), additive effect (Cl = 0.9-1.1) or antagonism / no benefit (Cl > 1.1), and provides the algorithm for the program. computer for automatic simulation for drug combinations. This takes into account the potency (the D(m) value) and the shape of the dose-effect curve (the m value) of each drug alone and their combinations. The Chou-Talalay combination index (Cl) can be estimated using the Synergy R package (see “Preclinical versus Clinical Drugs Combination Studies”, Chou TC. Leuk. Lymphoma. (2008);49(11):2059-2080, and the references cited therein, which are incorporated herein by reference in their entirety). The Cl of the combination can be assayed in a suitable cell line, eg, ABC-DLBLC cell lines (such as TMD8 or HBL1), eg, under the conditions used in Example 26. Preferably, the pharmaceutical combination of the invention is a synergistic combination where the Chou-Talalay Combination Index (Cl) is less than 0.9; 0.8; 0.7; 0.6; 0.5; 0.4; 0.3 or 0.2. Preferably, the Cl is 0.1-0.5, 0.1-0.3 or 0.1-0.2. In particular, a method of treating cancer in a patient is provided which comprises simultaneously, sequentially or separately administering to a patient in need thereof therapeutically effective synergistic amounts of components (A) and (B) of a pharmaceutical combination of the invention. . Also provided is a pharmaceutical combination of the invention for use in the treatment of cancer, wherein synergistic amounts of components (A) and (B) are administered to the patient simultaneously, separately or sequentially for the treatment of cancer. Preferably, amounts of components (A) and (B) are administered to the patient in order to provide the plasma concentrations disclosed above. Also provided is the use of synergistic amounts of components (A) and (B) of the pharmaceutical combination of the invention in the manufacture of a pharmaceutical combination for simultaneous, separate or sequential use for the treatment of cancer. Also provided is a synergistic pharmaceutical combination of the invention for use in treatment or for use as a medicament. In some methods, two or more anti-LY75 monoclonal antibodies with different binding specificities are administered simultaneously, in which case the dosage of i ccc i n / nznz / E / YiAi for each administered antibody falls within the indicated ranges. The antibody is generally administered multiple times. Intervals between single dosings can be, for example, daily, twice weekly, weekly, monthly, every three months, every six months, or annually. The intervals may also be irregular as indicated by measuring the blood levels of antibody against the target antigen in the patient. In some methods, the dosage is adjusted to achieve a plasma antibody concentration of approximately 1-1000 pg / ml, 5-750 pg / ml, 10-600 pg / ml, 15-500 pg / ml, 20-400 pg. / ml and in some methods approximately 25-300 pg / ml. Alternatively, the anti-LY75 antibody can be administered as sustained release formulations, in which case less frequent administration is required. Dosage and frequency vary depending on the half-life of the antibody in the patient. In general, human antibodies show the longest half-life, followed by humanized antibodies, chimeric antibodies, and non-human antibodies. The dosage and frequency of administration may vary depending on whether the treatment is prophylactic or therapeutic. In prophylactic applications, a relatively low dosage is administered at relatively infrequent intervals over a long period of time. Some patients continue to receive treatment for the rest of their lives. In therapeutic applications, a relatively high dosage is sometimes required at relatively short intervals until the progress of the disease is slowed or terminated, and preferably until the patient shows partial or complete improvement in the symptoms of the disease. The patient can then be administered a prophylactic regimen. Actual dosage levels of the active ingredients in the pharmaceutical combinations of the present invention may vary so as to obtain an amount of the active ingredient that is effective in achieving the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. The dosage level selected will depend on a variety of pharmacokinetic factors including the activity of the particular compositions of the present invention employed, or the ester, salt or amide thereof, the route of administration, the time of administration, the rate of excretion of the particular compound being used, duration of treatment, other drugs, compounds and / or materials used in combination with the particular compositions used, the age, sex, weight, condition, general health and previous medical history of the patient being treated, and similar factors well known in the medical arts. A "therapeutically effective dosage" of an anti-LY75 antibody preferably results in a decrease in the severity of disease symptoms, an increase in the frequency and duration of symptom-free periods of i ccc i η / ηζηζ / Ε / γίΛΐ disease, or a prevention of impairment or disability due to disease. For example, for the treatment of LY75-mediated tumors, a "therapeutically effective dosage" preferably inhibits cell growth or tumor growth by at least about 20%, at least about 30%, more preferably by at least about 40%, at least about 50% even more preferably at least about 60%, at least about 70%, and even more preferably at least about 80% or at least about 90%, relative to the subjects not treated. The ability of a compound to inhibit tumor growth can be assessed in an animal model system that predicts efficacy in human tumors. Alternatively, this property of a composition can be evaluated by examining the compound's ability to inhibit cell growth, such inhibition can be measured in vitro by assays known to those skilled in the art. A therapeutically effective amount of a therapeutic compound can decrease tumor size, or otherwise alleviate symptoms in a subject. One skilled in the art could determine such amounts based on factors such as the size of the subject, the severity of the subject's symptoms, and the particular composition or route of administration selected. A pharmaceutical combination of the present invention may be administered via one or more routes of administration using one or more of a variety of methods known in the art. Components (A) and (B) can be administered by the same route or by different routes. As those skilled in the art will appreciate, the route and / or mode of administration will vary depending on the desired results. Preferred routes of administration for the antibodies of the invention include intravenous, intramuscular, intradermal, intraperitoneal, subcutaneous, spinal or other parenteral routes of administration, for example by injection or infusion. The phrase "parenteral administration" in the present context means modes of administration other than enteral and topical administration, generally by injection, and includes, but is not limited to, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac injection and infusion. , intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, epidural and intrasternal. Alternatively, the anti-LY75 antibody can be administered via a non-parental route of administration, such as a topical, epidermal, mucosal route, eg, intranasally, orally, vaginally, rectally, sublingually, or topically. Preferably Venetoclax or a pharmaceutically acceptable salt thereof is administered orally, for example in a tablet. Active compounds can be prepared with carriers that will protect the compound against rapid release, such as a controlled release formulation, including implants, transdermal patches, and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Many methods for the preparation of such formulations are proprietary or generally known to those skilled in the art [see, for example, Sustained and Controlled Release Drug Delivery Systems (1978) J.R. Robinson, ed., Marcel Dekker, Inc., N.Y]. The therapeutic compositions can be administered with medical devices known in the art. For example, in a preferred embodiment, component (A) and / or component (B) can be administered with a needleless hypodermic injection device, such as the devices described in US Patent Nos. 5,399,163; 5,383,851; 5,312,335; 5,064,413; 4,941,880; 4,790,824; or 4,596,556. Examples of well-known implants and modules useful in the present invention include: US Patent No. 4,487,603, which describes an implantable microinfusion pump for dispensing medication at a controlled rate; US Patent No. 4,486,194, which describes a therapeutic device for delivering drugs through the skin; US Patent No. 4,447,233, which describes a drug infusion pump for delivering drug at a precise infusion rate; US Patent No. 4,447,224, which describes a variable flow implantable infusion device for continuous drug delivery; US Patent No. 4,439,196, which describes an osmotic drug delivery system having multi-chamber compartments; and US Patent No. 4,475,196, which describes an osmotic drug delivery system. These patents are incorporated herein by reference. Many other such implants, delivery systems, and modules are known to those skilled in the art. In certain embodiments, anti-LY75 antibodies can be formulated to ensure proper distribution in vivo. For example, the blood brain barrier (BBB) ​​excludes many highly hydrophilic compounds. To ensure that therapeutics cross the BBB (if desired), they can be formulated, for example, in liposomes. For methods of manufacturing liposomes, see, for example, US Patent Nos. 4,522,811; 5,374,548; and 5,399,331. Liposomes may comprise one or more moieties which are selectively transported into specific cells or organs, thereby enhancing targeted drug delivery [see, for example V.V. Ranade (1989) J. Clin. Pharmacol. 29:685]. Examples of targeting moieties include folate or biotin (see, for example, US Patent Ne5,416,016); mannosides [Umezawa et al. (1988) Biochem. Biophys. Res. Comm. 153:1038]; i cci η / ηζηζ / Ε / γ antibodies [P.G. Bloeman et al. (1995) FEBS Lett. 357:140; M. Owais et al. (1995) Antimicrob. Agents Chemother. 39:180]; surfactant Protein A receptor [Briscoe et al. (1995) Am. J. Physiol. 1233:134]; p120 [Schreier et al. (1994) J. Biol. Chem. 269:9090]; see also K. Keinanen; M.L. Laukkanen (1994) FEBS Lett. 346:123; J.J. Killion; LJ. Fidler (1994) Immunomethods 4:273. Uses and Methods In the present context, the term "subject" is intended to include human and non-human animals. Non-human animals include all vertebrates, for example mammals and non-mammals, such as non-human primates, sheep, dogs, cats, cows, horses, chickens, amphibians, and reptiles. Preferred subjects include human patients having disorders mediated by LY75 activity. In some preferred embodiments, the subject is a human subject who has a 17p deletion, eg, one that is characteristic of chronic lymphocytic leukemia. The methods are particularly suitable for treating human patients having a disorder associated with aberrant LY75 expression. Given the expression of LY75 on tumor cells, the combinations and methods of the present invention can be used to treat a subject with a tumorigenic disorder, for example, a disorder characterized by the presence of tumor cells that express LY75 or in the making of a drug for the treatment of said disorder, including, for example, leukemia, including chronic lymphocytic leukemia and acute myeloid leukemia, non-Hodgkin lymphoma, including DLBCL, B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, tissue lymphoma mucosa-associated lymphoid (MALT), B-cell lymphoma, T-cell / histiocyte-rich, Burkitt's lymphoma, lymphoplasmacytic lymphoma, small lymphocytic lymphoma, marginal zone lymphoma, T-cell lymphoma, peripheral T-cell lymphoma, anaplastic lymphoma of large cell and angioimmunoblastic T-cell lymphoma. LY75 has been shown to be internalized upon antibody binding as illustrated in Examples 5 and 7 below, thus allowing LY75 antibodies to be used in any payload mechanism of action, for example, in an ADC (antibody-drug conjugates), radioimmunoconjugates, or ADEPT (enzyme treatment) strategy. with antibody-directed prodrug). Anti-LY75 antibodies, generally administered as ADCs, can be used to inhibit or block LY75 function which, in turn, may be linked to the prevention or amelioration of certain disease symptoms, thereby implicating LY75 as a disease mediator. This can be accomplished by contacting a sample and a control sample with the anti-LY75 antibody under conditions that result in the formation of a complex between the antibody and LY75. Any complex formed between the antibody and LY75 is detected and compared in the sample and control. i ccc n / nznz / B / v Suitable routes for administering antibody compositions (eg, monoclonal antibodies and immunoconjugates) in vivo and in vitro are well known in the art and can be selected by those skilled in the art. For example, the antibody compositions can be administered by injection (eg intravenous or subcutaneous). Suitable dosages of the molecules used will depend on the age and weight of the subject and the concentration and / or formulation of the antibody composition. As previously described, anti-LY75 antibodies can be administered in conjunction with one or other therapeutic agents, for example with a cytotoxic agent, a radiotoxic agent or an immunosuppressive agent. The antibody can be linked to the agent (as an immune complex) or it can be administered separately from the agent. In the latter case (separate administration), the antibody can be administered before, after or concurrently with the agent or it can be administered in conjunction with other known therapies, eg anti-cancer therapy, eg radiation. Such therapeutic agents include, among others, antineoplastic agents such as doxorubicin (adriamycin), bleomycin sulfate cisplatin, carmustine, chlorambucil, and cyclophosphamide hydroxyurea which, by themselves, are only effective at levels that are toxic or subtoxic to a patient. Cisplatin is administered intravenously as a 100 mg / kg dose once every four weeks and adriamycin is administered intravenously as a 60-75 mg / ml dose once every 21 days. Other agents suitable for co-administration with the antibodies of the invention include other agents used for the treatment of cancers, for example gastric cancer, colorectal cancer, prostate cancer, breast cancer, ovarian cancer or lung cancer, such as Avastin®, 5FU and gemcitabine. Co-administration of the anti-LY75 antibodies or their antigen-binding fragments of the present invention with chemotherapeutic agents provides two anticancer agents which work by different mechanisms which provide a cytotoxic effect for human tumor cells. Such co-administration can solve problems due to the development of drug resistance or due to a change in the antigenicity of the tumor cells that would render them non-reactive with the antibody. The pharmaceutical combinations of the invention can also be administered together with serum and / or complement. These compositions can be advantageous when the complement is located in close proximity to the antibodies. Alternatively, the antibodies and the complement or serum can be administered separately. Within the scope of the present invention there are also kits comprising components (A) and (B) together with instructions for use. The kit may further contain one or i ccc i n / nznz / E / YiAi plus additional reagents, such as an immunosuppressive reagent, a cytotoxic agent or a radiotoxic agent, or one or more additional antibodies (for example, an antibody having a complementary activity that binds to an epitope on the LY75 antigen other than the first antibody). Accordingly, patients treated with pharmaceutical combinations of the invention may be additionally administered (prior to, simultaneously with, or following administration of an antibody disclosed herein) with another therapeutic agent, such as a cytotoxic or radiotoxic agent, which improves or increases the therapeutic effect of the antibodies. In other embodiments, the subject may be further treated with an agent that modulates, eg, enhances or inhibits, the expression or activity of Fcy or Fcy receptors, eg, by treating the subject with a cytokine. Preferred cytokines for administration during treatment with the multispecific molecule include granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), English), interferon-γ (IFN—γ), and tumor necrosis factor (TNF). All references cited in this specification, including but not limited to all documents, publications, patents, patent applications, presentations, texts, reports, manuscripts, brochures, books, internet publications, newsletter articles, newspapers, fact sheets, product, and the like, are incorporated by reference in this specification in their entireties. The description of the references in this invention is merely for the purpose of synthesizing the statements made by its authors and it is not admitted in any way that any reference constitutes prior art and Applicants reserve the right to test the accuracy and relevance of the cited references. . While the foregoing invention has been described in some detail by way of illustration and example for purposes of elucidating its understanding, it will be readily apparent to those skilled in the art in light of the teachings of this invention that certain changes and modifications thereto without departing from the spirit or scope of the dependent claims. The present invention is further illustrated by the following examples which should not be construed as further limiting. Example 1: Generation of Human Monoclonal Antibodies Against the LY75 Antigen Following standard procedures, mice (IgG1 from xeno mice) were immunized with full-length LY75-transfected CHO cells. The specificity of antibodies raised against LY75 was tested by flow cytometry in HEK293 cells transfected with LY75 and later in i cci η / ηζηζ / Β / γ cells. ΗΤ29 expressing LY75. To test the ability of the antibodies to bind to the cell surface protein LY75, the antibodies were incubated with the LY75-expressing cells. Cells were washed in FACS buffer (DPBS, 2% FBS), centrifuged, and resuspended in 100μΙ of diluted primary LY75 antibody (also diluted in FACS buffer). The cell line-antibody complex was incubated on ice for 60 min and then washed twice with FACS buffer as described above. The cell-antibody pellet was resuspended in 100 μΙ of the diluted secondary antibody (also diluted in FACS buffer) and incubated on ice for 60 min. The pellet was washed as described above and resuspended in 200μΙ FACS buffer. Samples were loaded onto the BD FACScanto II flow cytometer and data analyzed using BD FACSdiva software (results not shown). Example 2: Structural Characterization of Monoclonal Antibodies against LY75 The cDNA sequences encoding the heavy and light chain variable regions of the LY75_A1 monoclonal antibody were obtained using standard PCR techniques and were sequenced using conventional DNA sequencing techniques. Antibody sequences can be mutagenized to revert back to germline residues at one or more residues. The nucleotide and amino acid sequences of the LY75_A1 heavy chain variable region are shown in SEQ ID NO: 3 and 1, respectively. The nucleotide and amino acid sequences of the LY75 A1 light chain variable region are shown in SEQ ID NO: 4 and 2, respectively. The LY75_A1 heavy chain nucleotide and amino acid sequences are shown in SEQ ID NO: 38 and 202, respectively. The nucleotide and amino acid sequences of the LY75 A1 light chain are shown in SEQ ID NO: 39 and 203, respectively. Comparison of the LY75_A1 heavy chain immunoglobulin sequence with known human germline immunoglobulin heavy chain sequences demonstrated that the LY75_A1 heavy chain utilizes a VH3-15 human germline VH segment and a human germline JH segment. JHJH4. Further analysis of the LY75 A1 VH sequence using the Kabat system of CDR region determination led to the delineation of the heavy chain CDR1, CDR2 and CDR3 regions as shown in SEQ ID NOs: 5, 6 and 7, respectively. The alignments of the CDR1, CDR2 and CDR3 VH sequences of LY75_A1 to the germline VH3-15 and germline JHJH4 sequence are shown in FIGURE 1. Comparison of the LY75_A1 light chain immunoglobulin sequence with known human germline immunoglobulin light chain sequences i ccc i n / nznz / E / YiAi demonstrated that the LY75_A1 light chain utilizes a human germline VK012 VK segment and a JK segment from the human germ line JKJK4. Subsequent analysis of the LY75_A1 VK sequence using the Kabat system of CDR region determination led to the delineation of the light chain CDR1, CDR2 and CDR3 regions as shown in SEQ ID NOs: 8, 9 and 10, respectively. The alignments of the LY75_A1 CDR1, CDR2 and CDR3 VK sequences to the germline VK012 and germline JKJK4 sequences are shown in FIGURE 2. Example 3: Immunohistochemistry Using Monoclonal Antibody Against LY75 Using the human monoclonal antibodies specific for LY75, immunohistochemistry was performed on FFPE HT-29 and A549 cell pellets, FFPE pancreatic cancer and non-Hodgkin lymphoma pools, and fresh frozen lymphoma / leukemia tumors, ovarian cancer sections. , pancreatic cancer, and breast cancer and normal tissue groups. Materials and methods Materials Xylenes (X5P-1gal) from Fisher Scientific, PA, United States of America. Histoprep 100% ethanol (HC-800-1 GAL) from Fisher Scientific, PA, USA. 10x Citrate buffer for heat-induced epitope retrieval (AP9003125) from Thermo Scientific, MA, USA. Thermo Scientific* Pierce* Peroxidase Suppressor (35000) from Thermo Scientific, MA, United States of America. Serum Free Protein Block (X0909) from Dako, CA, USA Secondary Antibody: Goat Anti-Human IgG Fab-FITC Conjugate (109-097003) from Jackson Immunoresearch, PA, USA Whole Molecule, Pure Human IgG Chrome (09-000-003) from Jackson Immunoresearch, PA, United States of America Tertiary antibody: mouse anti-FITC (ab10257) from Abcam, MA, USA Purified Human IgG Isotype Control (1-001 A) from R&D Systems, MN, USA Tween-20 (BP337-100) from Fisher Scientific, PA, USA Acetone (BP2403-4) from Fisher Scientific, PA, USA HRP Conjugated Polymer Dual Link EnVision+, Mouse and Rabbit (K4063) from Dako , CA, United States of America. DAB 2 Solution Kit (882014) from Invitrogen, NY, USA. Harris Hematoxylin (23-245-677) from Fisher Scientific, PA, United States of i cci η / ηζηζ / Ε / γ America. Faramount Mounting Medium (S302580) from Dako, CA, United States of America. Sections and tissue pools were purchased from US Biomax Inc., MD, United States of America or Origine, MD, United States of America. FFPE Slide Preparation: Deparaffinization and Rehydration FFPE slides were deparaffinized in xylene (2x3 minutes) then rehydrated through 1:1 xylene: 100% ethanol (1x3 minutes), 100% ethanol (2x3 minutes), 95% ethanol (1x3 minutes), ethanol 70% (1x3 minutes), 50% ethanol (1x3 minutes), and tap water (1x3 minutes). FFPE Slide Preparation: Antigen Retrieval (Microwave). The LY75 antigen was recovered using microwave heat, high power to boiling then low power for 10 min in 50 mL 1x citrate buffer in a Coplin jar. The slides were then allowed to cool to room temperature for another 15 min, then washed in tap water, 3 min. Circles were drawn around each tissue / TMA section with a hydrophobic barrier pen and the slides were then washed 3 times in PBS, 3 minutes each wash. Preparation of FF slides Slides were removed from -80C storage and allowed to dry at room temperature in the fume hood for 20-30 min. Slides were fixed for 10 min in ice-cold acetone at -20C, then allowed to dry for 20 min in the fume hood at room temperature. Slides were washed and rehydrated in PBS, 3 washes for 3 min each. Sections were outlined with a hydrophobic barrier pen. Preparation of antibody complexes The primary anti-LY75 antibody was diluted in serum free protein block (SFPB) to obtain a solution with a concentration 20 times higher than the desired final concentration (20 pg / mL for 1 pg / mL final). . The secondary antibody, goat anti-human immunoglobulin G (IgG) antigen-binding fragment (Fab), was similarly prepared in SFPB to create an equal concentration solution. Equal volumes of primary and secondary antibodies were combined in a labeled tube, mixed gently, and incubated for 3 minutes at room temperature, resulting in a primary antibody concentration 10 times the desired final concentration (10 pg / mL for 1 pg / mL final). This mixture was diluted 1:5 with SFPB, mixed gently, and incubated for 30 minutes at room temperature, resulting in a primary antibody concentration twice that of the desired final concentration (2 pg / mL to 1 pg / mL final). ). To produce the final dye complexes, a 1% (10 i cci η / ηζηζ / Ε / γ pg / pL) solution of human IgG in SFPB was prepared and an equal volume added to the primary / secondary antibody mixture. This combination was mixed gently and incubated at room temperature for 30 minutes, diluting the primary antibody concentration of the primary / secondary antibody mixture by half, resulting in the desired final primary antibody concentration (1 pg / mL). Immunostaining Meanwhile, endogenous tissue peroxidase activity was blocked by incubating the tissues with peroxidase suppressant for 5-10 min at RT in a humidified chamber. The slides were then washed in PBS 3x3 minutes each wash. Tissues were incubated in SFPB for 30 minutes at room temperature in a humidified chamber. The final staining complexes were applied to each section and / or group of tissues, and the slides were incubated for 30 min at room temperature in a humidified chamber. Then, the slides were washed once in PBS and once in PBST (PBS+0.125% Tween-20), 3 min each wash. Tertiary antibody mouse anti-FITC was applied at a concentration of 2 pg / mL for 30 min, room temperature, in a humidified chamber. Sections were then washed once in PBS and once in PBST, 3 min each wash. Dual Link EnVision+ anti-mouse / rabbit HRP-conjugated polymer was then applied to the tissues and the slides were incubated for 30 min at room temperature in a humidified chamber. The slides were then washed once in PBS, once in PBST, 3 min each wash. Tissues were incubated in DAB solution prepared according to manufacturer's instructions at room temperature for 10 min. The slides were then washed once in running tap water for 2 minutes and once in PBS for 3 minutes. Slides were counterstained with Hematoxylin for 30 seconds at room temperature, and washed with tap water. The slides were dried at room temperature for 30 minutes and then coverslips were mounted on the slides using Faramount mounting medium. Results LY75_A1 showed positivity in FFPE Triple Negative Breast Cancer samples, where 77% of the sections showed positive staining and 55% exhibited strong staining (+++). Staining for LY75 in normal FF tissues was generally absent to low. The ductal epithelium of the breast, salivary gland, and pancreas exhibited marked low to moderate staining, and the spleen gave low positive staining. Therefore, antibodies directed against LY75 may have utility as therapeutic and diagnostic agents in some of the cancers tested and possibly in other types of cancers that show LY75 expression. Example 4: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 in HT-29 Cells Materials Cell Separator (Non-Enzymatic Cell Dissociation) (MT-25-056CI) from Fisher Scientific, PA, USA PBS pH 7.4 (1X) (SH30028LS) from Fisher Scientific, PA, USA RPMI 1640 Medium (MT-10-041-CM) from Fisher Scientific, PA, USA Glo Cell Titer (G7572) from Promega, Wl, USA Method Cells were dissociated using a cell sorter and counted. 5e3 cells / well were spun down in a pellet (for cells in suspension, more can be used depending on cell doubling time, such as 10e3 cells / well). The pellet was resuspended in culture medium to a concentration of 1-5 cells / mL. 50 ul / well of cell suspension was added to wells of a 96-well plate, white-sided and clear-bottomed. Antibodies were diluted and titrated to 8 points (3-fold titers) corresponding to concentrations between 0-20 nM (twice assay concentrations). Antibodies or diluted media (for untreated samples) (50ul / well) were added to the appropriate wells. Excess medium (200ul / well) was added to the outer rows and columns of the plate to prevent evaporation. The plate was incubated for 72h at 37C. The plate was removed from the incubator and incubated at room temperature for 30 minutes. Meanwhile the Cell Titer Glo solution was thawed. The plate was tilted and washed 1x with 10 µl / well PBS (for cells in suspension, the plate is first spun down to pellet cells). Add 100ul / well PBS and 10Oul Cell titer glo to each well and triturate to mix. The plate was incubated in the dark at room temperature for 15 minutes and visualized by microscopy to ensure efficient cell lysis occurred. The plate was then read in a Glomax luminometer. Results The results illustrated in FIGURE 3A show a subpopulation of antibodies, known to bind LY75, which can induce cell death of HT-29 cells. This suggests that while antibodies can bind to LY75 only a few exhibit efficacy when conjugated to DM1. Then, the antibodies were selected from the subpopulation for subsequent analysis of cytotoxic activity. i ccci η / ηζηζ / Ε / γ Example 5: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM4 and Conjugated to DM1 in Colorectal Cancer Cells Materials Cell Separator (Non-Enzymatic Cell Dissociation) (MT-25-056CI) from Fisher Scientific, PA, USA PBS pH 7.4 (1X) (SH30028LS) from Fisher Scientific, PA, USA RPMI 1640 Medium (MT-10-041-CM) from Fisher Scientific, PA, USA Cell Titer Glo (G7572) from Promega, Wl, USA Method Cells were dissociated using a cell separator and counted. 5e3 cells / well were centrifuged to form a pellet (for cells in suspension, more may be used depending on doubling the cells time, such as 10e3 cells / well). The pellet was resuspended in culture medium to a concentration of 1-5 cells / mL. 50ul / well of cell suspension were added to wells of a 96-well plate, with a clear bottom and white sides. Antibodies were diluted and titrated to 8 points (3-fold titers) corresponding to concentrations between 0-20 nM (twice assay concentrations). Diluted or medium (for untreated samples) antibodies (50ul / well) were added to the appropriate wells. Excess medium (200ul / well) was added to the outer rows and columns of the plate to prevent evaporation. The plate was incubated for 72h at 37C. The plate was removed from the incubator and incubated at room temperature for 30 minutes. Meanwhile the Cell Titer Glo solution was thawed. The plate was vortexed and washed 1x with 100ul / well PBS (for cells in suspension, the plate is first spun down to pellet cells). Add 100ul / well PBS and 10ul Cell titer glo to each well and triturate to mix. The plate was incubated in the dark at room temperature for 15 minutes and visualized by microscopy to ensure efficient cell lysis occurred. The plate was then read in a Glomax luminometer. Results FIGURE 3B shows the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 and DM4 towards HT-29 cells. These results demonstrate an increase in cytotoxic activity proportional to the concentration of antibodies and other anti-LY75 antibodies conjugated to a toxin (selected from Example 1). i ccci η / ηζηζ / Ε / γ Example 6: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Lymphoma Cell Lines Materials Cell Separator (Non-Enzymatic Cell Dissociation) (MT-25-056CI) from Fisher Scientific, PA, USA PBS pH 7.4 (1X) (SH30028LS) from Fisher Scientific, PA, USA RPMI 1640 Medium (MT-10-041-CM) from Fisher Scientific, PA, USA Cell Titer Glo (G7572) from Promega, Wl, USA Method Cells were dissociated using a cell separator and counted. 5e3 cells / well were centrifuged to form a pellet (for cells in suspension, more can be used depending on doubling the cells time, such as 10e3 cells / well). The pellet was resuspended in culture medium to a concentration of 1-5 cells / mL. 50ul / well of cell suspension was added to wells of a 96-well plate with a clear bottom and white sides. Antibodies were diluted and titrated to 8 points (3-fold titers) corresponding to concentrations between 0-20 nM (twice assay concentrations). Diluted or medium (for untreated samples) antibodies (50ul / well) were added to the appropriate wells. Excess medium (200ul / well) was added to the outer rows and columns of the plate to prevent evaporation. The plate was incubated for 72h at 37C. The plate was removed from the incubator and incubated at room temperature for 30 minutes. Meanwhile the Cell Titer Glo solution was thawed. The plate was vortexed and washed 1x with 100ul / well PBS (for cells in suspension, the plate is first spun down to pellet cells). Add 100ul / well PBS and 10Oul Cell titer glo to each well and triturate to mix. The plate was incubated in the dark at room temperature for 15 minutes and visualized by microscopy to ensure efficient cell lysis occurred. The plate was then read in a Glomax luminometer. Results FIGURE 3C shows the cytotoxic activity of DM1 and DM4 conjugated anti-LY75 antibodies towards RAJL cells. FIGURE 3D shows the cytotoxic activity of DM1 and DM4 conjugated anti-LY75 antibodies towards Namalwa cells. FIGURE 3E shows the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 and DM4 towards Karpas 299 cells. These results demonstrate an increase in cytotoxic activity proportional to the concentration of antibodies and other anti-LY75 antibodies conjugated to DM1 and DM4 i cci η / ηζηζ / Ε / γ (selected from Example 1). Example 7: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Pancreatic Cancer Cell Lines Materials Cell Separator (Non-Enzymatic Cell Dissociation) (MT-25-056CI) from Fisher Scientific, PA, USA PBS pH 7.4 (1X) (SH30028LS) from Fisher Scientific, PA, USA RPMI 1640 Medium (MT-10-041 -CM) from Fisher Scientific, PA, USA Cell Titer Glo (G7572) from Promega, Wl, USA Method Cells were dissociated using a cell separator and counted. 5e3 cells / well were centrifuged to form a pellet (for cells in suspension, more can be used depending on doubling the cells time, such as 10e3 cells / well). The pellet was resuspended in culture medium to a concentration of 1-5 cells / mL. 50ul / well of cell suspension was added to wells of a 96-well plate with a clear bottom and white sides. Antibodies were diluted and titrated to 8 points (3-fold titers) corresponding to concentrations between 0-20 nM (twice assay concentrations). Diluted or medium (for untreated samples) antibodies (50ul / well) were added to the appropriate wells. Excess medium (200ul / well) was added to the outer rows and columns of the plate to prevent evaporation. The plate was incubated for 72h at 37C. The plate was removed from the incubator and incubated at room temperature for 30 minutes. Meanwhile the Cell Titer Glo solution was thawed. The plate was vortexed and washed 1x with 100ul / well PBS (for cells in suspension, the plate is first spun down to pellet cells). Add 10µl / well PBS and 10µl Cell titer glo to each well and triturate to mix. The plate was incubated in the dark at room temperature for 15 minutes and visualized by microscopy to ensure efficient cell lysis occurred. The plate was then read in a Glomax luminometer. Results FIGURE 3F shows the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 and DM4 towards BxPC3 cells. FIGURE 3G shows the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 and DM4 towards HupT4 cells. FIGURE 3H shows the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 and DM4 towards HPAFFII cells. These results demonstrate an increase in cytotoxic activity proportional to the concentration i ccc i n / nznz / E / YiAi of antibodies and of other anti-LY75 antibodies conjugated to DM1 and DM4 (selected from Example 1). Example 8: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Chronic Lymphocytic Leukemia Cell Lines Materials Cell Separator (Non-Enzymatic Cell Dissociation) (MT-25-056CI) from Fisher Scientific, PA, USA PBS pH 7.4 (1X) (SH30028LS) from Fisher Scientific, PA, USA RPMI 1640 Medium (MT-10-041-CM) from Fisher Scientific, PA, USA Cell Titer Glo (G7572) from Promega, Wl, USA Method Cells were dissociated using a cell separator and counted. 5e3 cells / well were centrifuged to form a pellet (for cells in suspension, more can be used depending on doubling the cells time, such as 10e3 cells / well). The pellet was resuspended in culture medium to a concentration of 1-5 cells / mL. 50ul / well of cell suspension was added to wells of a 96-well plate with a clear bottom and white sides. Antibodies were diluted and titrated to 8 points (3-fold titers) corresponding to concentrations between 0-20 nM (twice assay concentrations). Diluted antibodies or medium (for untreated samples) (50ul / well) were added to the appropriate wells. Excess medium (200ul / well) was added to the outer rows and columns of the plate to prevent evaporation. The plate was incubated for 72h at 37C. The plate was removed from the incubator and incubated at room temperature for 30 minutes. Meanwhile the Cell Titer Glo solution was thawed. The plate was vortexed and washed 1x with 100ul / well PBS (for cells in suspension, the plate is first spun down to pellet cells). Add 10µl / well PBS and 10µl Cell titer glo to each well and triturate to mix. The plate was incubated in the dark at room temperature for 15 minutes and visualized by microscopy to ensure efficient cell lysis occurred. The plate was then read in a Glomax luminometer. Results FIGURE 3I shows the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 and DM4 towards EHEB cells. FIGURE 3J shows the cytotoxic activity of DM1 and DM4 conjugated anti-LY75 antibodies towards Mec-1 cells. These results demonstrate an increase in cytotoxic activity proportional to the concentration of antibodies and other i ccc i n / nznz / E / YiAi anti-LY75 antibodies conjugated to DM1 and DM4 (selected from Example 1). Example 9: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Acute Monocytic Leukemia Cell Lines Materials Cell Separator (Non-Enzymatic Cell Dissociation) (MT-25-056CI) from Fisher Scientific, PA, USA PBS pH 7.4 (1X) (SH30028LS) from Fisher Scientific, PA, USA RPMI 1640 Medium (MT-10-041 -CM) from Fisher Scientific, PA, USA Cell Titer Glo (G7572) from Promega, Wl, USA Method Cells were dissociated using a cell separator and counted. 5e3 cells / well were centrifuged to form a pellet (for cells in suspension, more can be used depending on doubling the cells time, such as 10e3 cells / well). The pellet was resuspended in culture medium to a concentration of 1-5 cells / mL. 50ul / well of cell suspension was added to wells of a 96-well plate with a clear bottom and white sides. Antibodies were diluted and titrated to 8 points (3-fold titers) corresponding to concentrations between 0-20 nM (twice assay concentrations). Diluted or medium (for untreated samples) antibodies (50ul / well) were added to the appropriate wells. Excess medium (200ul / well) was added to the outer rows and columns of the plate to prevent evaporation. The plate was incubated for 72h at 37C. The plate was removed from the incubator and incubated at room temperature for 30 minutes. Meanwhile the Cell Titer Glo solution was thawed. The plate was vortexed and washed 1x with 100ul / well PBS (for cells in suspension, the plate is first spun down to pellet cells). Add 100ul / well PBS and 10ul Cell titer glo to each well and triturate to mix. The plate was incubated in the dark at room temperature for 15 minutes and visualized by microscopy to ensure efficient cell lysis occurred. The plate was then read in a Glomax luminometer. Results FIGURE 3K shows the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 and DM4 towards AML-193 cells. These results demonstrate an increase in cytotoxic activity proportional to the concentration of antibodies and other anti-LY75 antibodies conjugated to DM1 and DM4 (selected from Example 1). i ccc i n / nznz / E / YiAi Example 10: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Breast Cancer Cell Lines Materials Cell Separator (Non-Enzymatic Cell Dissociation) (MT-25-056CI) from Fisher Scientific, PA, USA PBS pH 7.4 (1X) (SH30028LS) from Fisher Scientific, PA, USA RPMI 1640 Medium (MT-10-041-CM) from Fisher Scientific, PA, USA Cell Titer Glo (G7572) from Promega, Wl, USA Method Cells were dissociated using a cell separator and counted. 5e3 cells / well were centrifuged to form a pellet (for cells in suspension, more can be used depending on doubling the cells time, such as 10e3 cells / well). The pellet was resuspended in culture medium to a concentration of 1-5 cells / mL. 50ul / well of cell suspension was added to wells of a 96-well plate with a clear bottom and white sides. Antibodies were diluted and titrated to 8 points (3-fold titers) corresponding to concentrations between 0-20 nM (twice assay concentrations). Diluted or medium (for untreated samples) antibodies (50ul / well) were added to the appropriate wells. Excess medium (200ul / well) was added to the outer rows and columns of the plate to prevent evaporation. The plate was incubated for 72h at 37C. The plate was removed from the incubator and incubated at room temperature for 30 minutes. Meanwhile the Cell Titer Glo solution was thawed. The plate was vortexed and washed 1x with 100ul / well PBS (for cells in suspension, the plate is first spun down to pellet cells). Add 10µl / well PBS and 10µl Cell titer glo to each well and triturate to mix. The plate was incubated in the dark at room temperature for 15 minutes and visualized by microscopy to ensure efficient cell lysis occurred. The plate was then read in a Glomax luminometer. Results FIGURE 3L shows the cytotoxic activity of DM1 and DM4 conjugated anti-LY75 antibodies towards HCC 70 cells (ER negative, PR negative and Her2 negative). FIGURE 3M shows the cytotoxic activity of DM1 and DM4 conjugated anti-LY75 antibodies towards HCC 1806 cells (ER negative, PR negative and Her2 negative). FIGURE 3N shows the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 and DM4 towards MDA-MB-468 cells. These results demonstrate an increase in the cytotoxic activity i cci η / ηζηζ / Ε / γ proportional to the concentration of antibodies. Example 11: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Bladder Cancer Cell Lines Materials Cell Separator (Non-Enzymatic Cell Dissociation) (MT-25-056CI) from Fisher Scientific, PA, USA PBS pH 7.4 (1X) (SH30028LS) from Fisher Scientific, PA, USA RPMI 1640 Medium (MT-10-041 -CM) from Fisher Scientific, PA, USA Cell Titer Glo (G7572) from Promega, Wl, USA Method Cells were dissociated using a cell separator and counted. 5e3 cells / well were centrifuged to form a pellet (for cells in suspension, more can be used depending on doubling the cells time, such as 10e3 cells / well). The pellet was resuspended in culture medium to a concentration of 1-5 cells / mL. 50ul / well of cell suspension was added to wells of a 96-well plate with a clear bottom and white sides. Antibodies were diluted and titrated to 8 points (3-fold titers) corresponding to concentrations between 0-20 nM (twice assay concentrations). Diluted or medium (for untreated samples) antibodies (50ul / well) were added to the appropriate wells. Excess medium (200ul / well) was added to the outer rows and columns of the plate to prevent evaporation. The plate was incubated for 72h at 37C. The plate was removed from the incubator and incubated at room temperature for 30 minutes. Meanwhile the Cell Titer Glo solution was thawed. The plate was vortexed and washed 1x with 100ul / well PBS (for cells in suspension, the plate is first spun down to pellet cells). Add 100ul / well PBS and 10ul Cell titer glo to each well and triturate to mix. The plate was incubated in the dark at room temperature for 15 minutes and visualized by microscopy to ensure efficient cell lysis occurred. The plate was then read in a Glomax luminometer. Results FIGURE 30 shows the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 and DM4 towards RT4 cells. FIGURE 3P shows the cytotoxic activity of DM1 and DM4 conjugated anti-LY75 antibodies towards 5637 cells. FIGURE 3Q shows the cytotoxic activity of DM1 and DM4 conjugated anti-LY75 antibodies towards SW780 cells. These results demonstrate an increase in cytotoxic activity proportional to the concentration i cci η / ηζηζ / Ε / γ of antibodies. Example 12: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Head and Neck Cancer Cell Lines Materials Cell Separator (Non-Enzymatic Cell Dissociation) (MT-25-056CI) from Fisher Scientific, PA, USA PBS pH 7.4 (1X) (SH30028LS) from Fisher Scientific, PA, USA RPMI 1640 Medium (MT-10-041 -CM) from Fisher Scientific, PA, USA Cell Titer Glo (G7572) from Promega, Wl, USA Method Cells were dissociated using a cell separator and counted. 5e3 cells / well were centrifuged to form a pellet (for cells in suspension, more can be used depending on doubling the cells time, such as 10e3 cells / well). The pellet was resuspended in culture medium to a concentration of 1-5 cells / mL. 50ul / well of cell suspension was added to wells of a 96-well plate with a clear bottom and white sides. Antibodies were diluted and titrated to 8 points (3-fold titers) corresponding to concentrations between 0-20 nM (twice assay concentrations). Diluted or medium (for untreated samples) antibodies (50ul / well) were added to the appropriate wells. Excess medium (200ul / well) was added to the outer rows and columns of the plate to prevent evaporation. The plate was incubated for 72h at 37C. The plate was removed from the incubator and incubated at room temperature for 30 minutes. Meanwhile the Cell Titer Glo solution was thawed. The plate was vortexed and washed 1x with 100ul / well PBS (for cells in suspension, the plate is first spun down to pellet cells). Add 100ul / well PBS and 10ul Cell titer glo to each well and triturate to mix. The plate was incubated in the dark at room temperature for 15 minutes and visualized by microscopy to ensure efficient cell lysis occurred. The plate was then read in a Glomax luminometer. Results FIGURE 3R shows the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 and DM4 towards SCC-9 cells. These results demonstrate an increase in cytotoxic activity proportional to the concentration of antibodies. i ccc i n / nznz / E / YiAi Example 13: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Esophageal Cancer Cell Lines Materials Cell Separator (Non-Enzymatic Cell Dissociation) (MT-25-056CI) from Fisher Scientific, PA, USA PBS pH 7.4 (1X) (SH30028LS) from Fisher Scientific, PA, USA RPMI 1640 Medium (MT-10-041 -CM) from Fisher Scientific, PA, USA Cell Titer Glo (G7572) from Promega, Wl, USA Method Cells were dissociated using a cell separator and counted. 5e3 cells / well were centrifuged to form a pellet (for cells in suspension, more can be used depending on doubling the cells time, such as 10e3 cells / well). The pellet was resuspended in culture medium to a concentration of 1-5 cells / mL. 50ul / well of cell suspension was added to wells of a 96-well plate with a clear bottom and white sides. Antibodies were diluted and titrated to 8 points (3-fold titers) corresponding to concentrations between 0-20 nM (twice assay concentrations). Diluted or medium (for untreated samples) antibodies (50ul / well) were added to the appropriate wells. Excess medium (200ul / well) was added to the outer rows and columns of the plate to prevent evaporation. The plate was incubated for 72h at 37C. The plate was removed from the incubator and incubated at room temperature for 30 minutes. Meanwhile the Cell Titer Glo solution was thawed. The plate was vortexed and washed 1x with 100ul / well PBS (for cells in suspension, the plate is first spun down to pellet cells). Add 100ul / well PBS and 10ul Cell titer glo to each well and triturate to mix. The plate was incubated in the dark at room temperature for 15 minutes and visualized by microscopy to ensure efficient cell lysis occurred. The plate was then read in a Glomax luminometer. Results FIGURE 3S shows the cytotoxic activity of DM1 and DM4 conjugated anti-LY75 antibodies towards OE 19 cells. These results demonstrate an increase in cytotoxic activity proportional to antibody concentration. i ccci η / ηζηζ / Ε / γ Example 14: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Ovarian Cancer Cell Lines Materials Cell Separator (Non-Enzymatic Cell Dissociation) (MT-25-056CI) from Fisher Scientific, PA, USA PBS pH 7.4 (1X) (SH30028LS) from Fisher Scientific, PA, USA RPMI 1640 Medium (MT-10-041-CM) from Fisher Scientific, PA, USA Cell Titer Glo (G7572) from Promega, Wl, USA Method Cells were dissociated using a cell separator and counted. 5e3 cells / well were centrifuged to form a pellet (for cells in suspension, more can be used depending on doubling the cells time, such as 10e3 cells / well). The pellet was resuspended in culture medium to a concentration of 1-5 cells / mL. 50ul / well of cell suspension was added to wells of a 96-well plate with a clear bottom and white sides. Antibodies were diluted and titrated to 8 points (3-fold titers) corresponding to concentrations between 0-20 nM (twice assay concentrations). Diluted or medium (for untreated samples) antibodies (50ul / well) were added to the appropriate wells. Excess medium (200ul / well) was added to the outer rows and columns of the plate to prevent evaporation. The plate was incubated for 72h at 37C. The plate was removed from the incubator and incubated at room temperature for 30 minutes. Meanwhile the Cell Titer Glo solution was thawed. The plate was vortexed and washed 1x with 100ul / well PBS (for cells in suspension, the plate is first spun down to pellet cells). Add 100ul / well PBS and 10ul Cell titer glo to each well and triturate to mix. The plate was incubated in the dark at room temperature for 15 minutes and visualized by microscopy to ensure efficient cell lysis occurred. The plate was then read in a Glomax luminometer. Results FIGURE 3T shows the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 and DM4 towards OVCAR-3 cells. FIGURE 3U shows the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 and DM4 towards SK-OV-3 cells. These results demonstrate an increase in cytotoxic activity proportional to the concentration of antibodies. i ccci η / ηζηζ / Ε / γ Example 15: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Multiple Myeloma Cell Lines Materials Cell Separator (Non-Enzymatic Cell Dissociation) (MT-25-056CI) from Fisher Scientific, PA, USA PBS pH 7.4 (1X) (SH30028LS) from Fisher Scientific, PA, USA RPMI 1640 Medium (MT-10-041 -CM) from Fisher Scientific, PA, USA Cell Titer Glo (G7572) from Promega, Wl, USA Method Cells were dissociated using a cell separator and counted. 5e3 cells / well were centrifuged to form a pellet (for cells in suspension, more can be used depending on doubling the cells time, such as 10e3 cells / well). The pellet was resuspended in culture medium to a concentration of 1-5 cells / mL. 50ul / well of cell suspension was added to wells of a 96-well plate with a clear bottom and white sides. Antibodies were diluted and titrated to 8 points (3-fold titers) corresponding to concentrations between 0-20 nM (twice assay concentrations). Diluted or medium (for untreated samples) antibodies (50ul / well) were added to the appropriate wells. Excess medium (200ul / well) was added to the outer rows and columns of the plate to prevent evaporation. The plate was incubated for 72h at 37C. The plate was removed from the incubator and incubated at room temperature for 30 minutes. Meanwhile the Cell Titer Glo solution was thawed. The plate was vortexed and washed 1x with 100ul / well PBS (for cells in suspension, the plate is first spun down to pellet cells). 100ul / well PBS and 100μΙ Cell titer glo were added to each well and triturated to mix. The plate was incubated in the dark at room temperature for 15 minutes and visualized by microscopy to ensure efficient cell lysis occurred. The plate was then read in a Glomax luminometer. Results FIGURE 3V shows the cytotoxic activity of anti-LY75 antibodies conjugated to DM1 and DM4 towards MOLP-8 cells. FIGURE 3W shows the cytotoxic activity of DM1 and DM4 conjugated anti-LY75 antibodies towards RPMI8226 cells. These results demonstrate an increase in cytotoxic activity proportional to the concentration of antibodies. i ccci η / ηζηζ / Β / γ Example 16: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Raü Xenograft Models The efficacy of LY75_DM1 and LY75_DM4 was tested in a SCID mouse xenograft model of subcutaneous Raji Burkitt lymphoma. Immunodeficient SCID mice were inoculated subcutaneously with Raji (human Burkitt's lymphoma) tumor cells. Tumors were allowed to establish and mice were distributed into five treatment groups of 3-6 mice per group. When the mean tumor volume reached an average size of 129-132 mm3 per group, each group was treated with one of the following compounds, administered intravenously at the indicated doses: Group 1 (Vehicle; phosphate buffered saline (PBS, for its acronym in English)); Group 2 (LY75_DM1; 10 mg / kg), Group 3 (Control isotype-DM1; 10 mg / kg), Group 4 (LY75_DM4; 5 mg / kg), Group 5 (control isotype-SPBDDM4; 5 mg / kg) . A second dose was administered one week later. Body weights (BWs) were monitored, mice were frequently examined for adverse side effects and health, and tumors were measured twice weekly. Mice were euthanized when their tumors reached the tumor volume endpoint of 2000 mm3 or after 60 days, whichever came first. Efficacy was determined from tumor growth delay (TGD), increased time to endpoint (TTE), and from logrank analysis of the differences in Kaplan Meier survival curves in ADC-treated mice compared to PBS-treated mice. Samples were obtained from the first five vehicle-treated control mice to reach endpoint for tumors that were processed by formalin fixation and paraffin embedded. Results FIGURE 4A shows that LY75 DM1 and LY75 DM4 each demonstrated significant antitumor activity and significantly extended survival in the SCID mouse xenograft model of Raji Burkitt lymphoma compared to controls; however, 5 mg / kg doses of LY75_DM4 were significantly more effective than 10 mg / kg doses of LY75_DM1, resulting in 5 of 6 mice with complete but transient tumor regression. All treatments were well tolerated and no clinical signs of toxicity were observed. These data suggest the potential for ADCs directed towards LY75, eg LY75 DM1 and LY75 DM4, to provide clinical benefit in the treatment of human non-Hodgkin lymphoma cancer patients. Example 17: Efficacy of DM1-Conjugated and DM4-Conjugated Anti-LY75 Monoclonal Antibodies in Namalwa Xenograft Models The efficacy of LY75 DM1 and LY75 DM4 was tested in a subcutaneous Namalwa Burkitt lantern SCID i cci η / ηζηζ / Ε / γ mouse xenograft model. Immunodeficient SCID mice were inoculated subcutaneously with Namalwa (human Burkitt's lymphoma) tumor cells. Tumors were allowed to establish and mice were distributed into five treatment groups of 6 mice per group. When the mean tumor volume reached an average size of 114 mm3 per group, each group was treated with one of the following compounds, administered intravenously at the indicated doses: Group 1 (Vehicle; phosphate buffered saline (PBS)); Group 2 (LY75_DM1; 10 mg / kg), Group 3 (Control isotype-DM1; 10 mg / kg), Group 4 (LY75_DM4; 5 mg / kg), Group 5 (Control isotype-SPBDDM4; 5 mg / kg). Body weights (BW) were monitored, mice were frequently examined for health and adverse side effects, and tumors were measured twice weekly. Mice were euthanized when their tumors reached the tumor volume endpoint of 2000 mm3 or after 60 days, whichever occurs first. Efficacy was determined from tumor growth delay (TGD), increase in median time to endpoint (TTE), and from log-rank analysis of differences in Kaplan Meier survival curves in treated mice. with ADC compared to those treated with PBS. Samples were obtained from the first five vehicle-treated control mice to reach the endpoint for tumors that were processed by formalin fixation and paraffin embedded. Results FIGURE 4B shows that LY75 DM1 and LY75DM4 each demonstrated significant antitumor activity and extension of survival in the xenograft model in Namalwa Burkitt lymphoma SCID mice compared to controls; however, the 5 mg / kg dose of LY75_DM4 was significantly more effective than the 10 mg / kg dose of LY75 DM1, causing a brief reduction in tumor volume. All treatments were well tolerated and no clinical signs of toxicity were observed. These data suggest the potential for ADCs directed towards LY75, eg LY75_DM1 and LY75_DM4, to provide clinical benefit in the treatment of human non-Hodgkin lymphoma cancer patients. Example 18: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Pancreatic Cancer Xenograft Models The efficacy of LY75 DM1 and LY75 DM4 was tested in the xenograft model in athymic nude mice of subcutaneous HPAFII pancreatic adenocarcinoma. Immunodeficient athymic nude mice were inoculated subcutaneously with HPAFII (human pancreatic adenocarcinoma) tumor cells. Tumors were allowed to establish and mice were distributed into five treatment groups of 6 mice per group. When the mean tumor volume reached a mean size of -114 mm3 / group, each group was treated with one of the following compounds, administered intravenously at the indicated doses: Group 1 (Vehicle; phosphate buffered saline (PBS)); Group 2 (LY75_DM1; 10 mg / kg), Group 3 (Control isotype-DM1; 10 mg / kg), Group 4 (LY75_DM4; 5 mg / kg), Group 5 (Control isotype-SPBDDM4; 5 mg / kg). Body weights (BWs) were monitored, mice were frequently examined for health and adverse side effects, and tumors were measured three times a week. Mice were euthanized when their tumors reached the tumor volume endpoint of 2000 mm3 or after 90 days, whichever came first. Efficacy was determined from the effect of treatment on tumor volume and from log-rank analysis of the differences in Kaplan-Meier survival curves in mice treated with ADC or PBS. Tumor samples were obtained from vehicle-treated control mice and processed by formalin fixation and paraffin embedded. Results FIGURE 4C shows that LY75 DM1 and LY75DM4 exhibited significant and similarly potent antitumor activity and extension of survival in the HPAFII nude mouse xenograft model compared to controls. All treated were well tolerated and no clinical signs of toxicity were observed. These data suggest the potential for ADCs directed towards LY75, eg LY75_DM1 and LY75_DM4, to provide clinical benefit in the treatment of human patients with pancreatic cancer. Example 19: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Xenograft Models of Bladder Cancer The efficacy of LY75 DM1 and LY75 DM4 was tested in the SCID mouse xenograft model with subcutaneous SW780 human bladder carcinoma. Immunodeficient athymic nude mice were inoculated subcutaneously with HPAFII (human pancreatic adenocarcinoma) tumor cells. Tumors were allowed to establish and mice were distributed into five treatment groups of 6 mice per group. When the mean tumor volume reached a mean size of ~114 mm3 / group, each group was treated with one of the following compounds, administered intravenously at the indicated doses: Group 1 (Vehicle; phosphate buffered saline (PBS)); Group 2 (LY75_DM1; 1 mg / kg), Group 3 (LY75_DM1; 2.5 mg / kg), Group 4 (LY75_DM1; 5 mg / kg), Group 5 (LY75_DM4; 1 mg / kg), Group 6 ( LY75_DM4; 2.5 mg / kg) ), Group 7 (LY75_DM4; 5 mg / kg) ), Group 8 (Isotype control-SPBDDM4; 5 mg / kg). Body weights (BWs) were monitored, mice were frequently examined for health and adverse side effects, and tumors were measured three times a week. Mice were euthanized i ccc i n / nznz / E / YiAi when their tumors reached the tumor volume endpoint of 2000 mm3 or after 90 days, whichever came first. Efficacy was determined from the effect of treatment on tumor volume and from log-rank analysis of the differences in Kaplan-Meier survival curves in mice treated with ADC or PBS. Tumor samples were obtained from vehicle-treated control mice and processed by formalin fixation and paraffin embedded. Results FIGURE 4D shows that LY75_DM1 and LY75_DM4 exhibited significant and similarly potent antitumor activity and extension of survival in the SW780 nude mouse xenograft model compared to controls. All treatments were well tolerated and no clinical signs of toxicity were observed. These data suggest the potential for LY75-directed ADCs, eg LY75_DM1 and LY75_DM4, to provide clinical benefit in the treatment of human bladder cancer patients. Example 20: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Xenograft Models of Breast Cancer The efficacy of LY75 DM1 and LY75 DM4 in the xenograft model was tested in subcutaneous MDA-MB-468 athymic nude mice. Immunodeficient athymic nude mice were inoculated subcutaneously with MDA-MB-468 (triple negative human breast adenocarcinoma) tumor cells. Tumors were allowed to establish and mice were distributed into seven treatment groups of 10 mice per group. When the mean tumor volume reached an average size of 167 mm3 per group, each group was treated with one of the following compounds, administered intravenously at the indicated doses: Group 1 (Vehicle; 20 mM sodium succinate, pH 5.0, 6 trehalose %, 0.04% polysorbate); Group 2 (LY75 DM1; 5 mg / kg), Group 3 (LY75_DM1; 10 mg / kg), Group 4 (LY75_DM4; 5 mg / kg), Group 5 (LY75_DM4; 2.5 mg / kg), Group 6 (LY75_DM4; 1 mg / kg), Group 7 (control isotype-DM4; 5 mg / kg). Body weights (BWs) were monitored, mice were examined frequently for health and adverse side effects, and tumors were measured twice weekly. Mice were euthanized 82 days after tumor inoculation. Efficacy was determined from antitumor activity (mean tumor size in treatment groups / mean tumor size in control group x 100) and increase in median time to endpoint (TTE) in treated mice. with ADC compared to those treated with PBS. Samples of the five largest tumors in vehicle-treated control mice were obtained on day 71 post-inoculation and processed by formalin fixation and paraffin embedded. i ccci η / ηζηζ / Ε / γ Results FIGURE 4E shows that LY75_DM1 and LY75_DM4 each demonstrated dramatic antitumor activity in the MDA-MB-468 nude mouse xenograft model compared to controls. Dose-dependent activity was observed with LY75_DM4, where 2.5 and 5 mg / kg were much more potent than 1 mg / kg. At 5 mg / kg, LY75DM1 and LY75DM4 had similar efficacy. Sustained regressions in mean tumor volume were observed for LY75_DM1 at 10 and 5 mg / kg and LY75_DM4 at 5 and 2.5 mg / kg. All treatments were well tolerated and no clinical signs of toxicity were observed. These data suggest the potential for LY75-directed ADCs, eg, LY75_DM1 and LY75_DM4, to provide clinical benefit in the treatment of human triple-negative breast cancer patients. Example 21: Efficacy of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Xenograft Models of Colorectal Cancer The efficacy of LY75 DM1 and LY75 DM4 in the xenograft model was tested in athymic nude mice with subcutaneous COLO205 colorectal adenocarcinoma. Immunodeficient athymic nude mice were inoculated subcutaneously with COLO205 (human colorectal adenocarcinoma) tumor cells. Tumors were allowed to establish and mice were distributed into five treatment groups of 6 mice per group. When the mean tumor volume reached an average size of 117 mm3 per group, each group was treated with one of the following compounds, administered intravenously at the indicated doses: Group 1 (Vehicle; phosphate buffered saline (PBS)); Group 2 LY75_DM1; 10 mg / kg), Group 3 (Control isotype-DM1; 10mg / kg), Group 4 (LY75_DM4; 5 mg / kg), Group 5 (Control isotype-DM4; 5 mg / kg). A second dose was administered twelve days after the first. Body weights (BWs) were monitored, mice were examined frequently for health and adverse side effects, and tumors were measured twice weekly. Mice were euthanized when their tumors reached the tumor volume endpoint of 1000 mm 3 or after 60 days, whichever occurs first. Efficacy was determined from tumor growth delay (TGD), increase in median time to endpoint (TTE), and from log-rank analysis of differences in Kaplan Meier survival curves in mice treated with ADC compared to those treated with PBS. Samples were obtained from the first five vehicle-treated control mice to reach the endpoint for tumors that were processed by formalin fixation and paraffin embedded. Results FIGURE 4F shows that LY75 DM1 and LY75 DM4 exhibited similar modest antitumor activity and extension of survival in the xenograft model in i ccc i n / nznz / E / YiAi nude mice with COLO205 colorectal adenocarcinoma compared to controls. All treatments were well tolerated and no clinical signs of toxicity were observed. These data suggest the potential for LY75-directed ADCs, eg LY75_DM1 and LY75_DM4, to provide clinical benefit in the treatment of human colorectal cancer patients. Example 22: Toxicity of Anti-LY75 Monoclonal Antibodies Conjugated to DM1 and Conjugated to DM4 in Cvnomolgus Monkeys Six male monkeys were assigned to the study with 2 monkeys / group. Either vehicle (PBS), LY75_DM4 (cleavable) or LY75_DM1 (non-cleavable) was administered twice (on Day 1 and Day 29) by 15 minute intravenous infusion at 0 mg / kg / dose (PBS, vehicle ), 5 mg / kg / dose (LY75_DM4, dissociable) or 10 mg / kg / dose (LY75_DM1, non-dissociable). Blood samples for toxicokinetic evaluations were collected prior to dosing (Day 1), and 1, 2, 3, 7, 14, 21, and 28 days after each dose. Blood samples for clinical pathology analysis were collected prior to dosing initiation (Day 1), and 1, 3, 7, 14, 21, and 28 days post each dose (28 days post-1 dose was also served as the pre-dose time point for the second dose). All study animals were euthanized and necropsied after the final bleed on Day 57. Plasma separated from each bleed was isolated, frozen, and transported to Oxford BioTherapeutics, Inc. for analysis for concentration. of ADC by ELISA. Treatment-related clinical pathological findings included mild regenerative anemia and transient decreases in blood leukocyte profile most notably neutrophil counts. Anemia was observed in both the animals treated with 5 mg / kg LY75_DM4 and one of the two animals treated with 10 mg / kg LY75 DM1. Severe neutropenia with a nadir was observed at one week post-dose and rapid recovery in counts was observed in all animals; the nadir in absolute neutrophil count was lower in LY75_DM4-treated animals. There were no effects related to the article under study on the coagulation parameters APTT and PT. Changes in serum chemistry included transient increases in AST, CK, LDH (in 1 of 2 animals in each treatment group), and globulin following administration of 5 mg / kg of LY75 DM4 and 10 mg / kg of LY75DM1. In addition, a transient increase in ALT of liver-specific enzymes was observed only in the LY75_DM4-treated animals. The short duration of, and / or the magnitude of, the increases in chemical parameters suggest that they were not adverse. There were no urinalysis findings related to the test article. Upon necropsy examination after a 4-week recovery period, there were no treatment-related gross pathological findings or changes in absolute and relative body weights. The i ccci n / nznz / B / v histopathological findings only in the thyroid gland (an alteration in colloidal morphology in the follicles) and in the kidney (dilated tubules in the outer cortex), were considered of minimal severity; not associated with changes in other study parameters; and, non-adverse and of minimal toxicological importance. Conclusion: Repeated-dose treatment with two doses of 5 mg / kg LY75_DM4 or 10 mg / kg LY75_DM1 was well tolerated in cynomologus monkeys. All treatment-related toxicity findings were reversible after a 4-week recovery period. Example 23: Characterization of LY75 A1 Epitopes by Competitive Fluorescence Activated Cell Sorting (FACS) Binding Analysis Method COLO205 cells (ATCC, catalog # CCL-222) were detached from tissue culture flasks with the Cell Stripper (Cellgro, catalog # MT-25-056CI). Cells were washed and resuspended in FACS buffer (PBS + 2% FBS), neutralized with growth medium, and counted. Cells were plated at 50,000 cells per well in a V-Bottom 96-well plate. Cells were washed once with FACS buffer (PBS (Fisher, catalog # SH30028-03) + 2% FBS). . An anti-LY75 (Selected from Example 1) or LY75_A1 mAb was added to wells starting at 250 nM and serially diluted 3-fold and applied to relevant wells for 45 min on ice. Test wells that required one or more staining steps were left in FACS buffer as appropriate to ensure that final staining was completed simultaneously for all conditions tested. Two wells remained unstained in FACS buffer as controls. After incubation with blocking antibody, cells were washed twice in FACS buffer. Cells were resuspended in FACS buffer containing MCC-DM1 conjugated anti-LY75 mAb (1 nM) and incubated on ice for 45 min. Cells were washed as described above and resuspended in FACS buffer plus 1 pg / ml mouse anti-maytansine antibody and incubated on ice for 45 minutes. Cells were washed as described above and resuspended in FACS buffer containing 2 ug / ml goat anti-mouse kappa RPE. Cells were incubated on ice for 45 minutes and then washed as described above. Cells were resuspended in FACS buffer at 200 μΙ per well. Mean fluorescence intensity of each sample was determined using a Guava EasyCyte Plus HT Flow Cytometer (96-well plate formats) and raw data analyzed using Guava Cytosoft. i ccci η / ηζηζ / Ε / γ Results FIGURE 5A shows that blocking with anti-LY75-mAb-MCC-DM1 reduced anti-LY75 mAb binding. Analysis of LY75_A1 binding to COLO205 cells showed that LY75_A1 is unable to block the binding of anti-LY75-mAb-l\ / ICC-DI\ / l1 (see FIGURE 5B). Therefore, it can be determined that the anti-LY75 mAb and LY75_A1 are non-competitive antibodies and LY75_A1 recognizes a different and unique epitope of LY75 than that of other anti-LY75 antibodies. Example 24 LY75 A1 Epitope Characterization by Peptide Microarray Assay. methods Peptide microarray analysis was performed by LC Sciences, Houston TX, briefly, the method comprised the following steps:- Contiguous 8mer peptides from LY75 protein having an amino acid overlap spanning residues 216 to 1666 of the protein Full length LY75 were synthesized and immobilized on a microarray chip. The chip comprised three panels so the experiment was carried out in triplicate. The microarray was challenged with LY75_A1 to identify the peptides to which the antibody bound. The binding assay was carried out under the following conditions: The microarray comprising the contiguous peptides in triplicate was washed with 1 mL of 4aC binding buffer for 20 min. It was then incubated with 1 pg / mL of LY75_A1 in binding buffer (pH 7.0) at 4 °C for 2 hrs. The array was washed again with 0.5 mL of washing buffer at 4 °C for 30 min and then incubated with 25 ng / mL anti-human IgG Alexa 647 conjugate in binding buffer (pH 7.0) at 4 °C for 1 hr. . The array was again washed with 0.5 mL of washing buffer at 4SC for 30 min. The array was then scanned at 635 nm and PMT 500 and the signal intensity was recorded. The peptide was classified as detectable if it was present in at least 2 / 3 of the legal duplicates. The average signal intensity of the replications was reported as the final signal intensity. Results As can be seen from FIGS. 6A-6J the LY75 A1 antibody showed specific binding to a number of peptides located in the array. The maximum observed signal for LY75_A1 binding was 25000 (scale 1-65535), with the average signal for all points in the array being approximately 885. A signal intensity of 3000 was set as the background cut. ”) dot for non-specific binding. Based on the observed antibody binding signal intensity level potential epitope-forming sequences for LY75_A1 were identified. These regions are shown in FIGURES 6A i ccc i n / nznz / E / YiAi 6J and as SEQ ID NOs: 22-31. Example 25 LY75 A1 peptide interaction v precipitation assay ("pull down") Method 7.1 Interaction and precipitation test (“pull down”) Recombinant LY75 protein was digested by on-bead tryptic proteolysis (Promega, USA). The resulting digest peptides were recovered using a C18 capture column (Thermo Fisher Scientific). The purified peptides were then incubated with 200 μΙ protein A beads cross-linked with LY75A1 antibody overnight at 4°C. The next day, unbound peptides were collected and the beads were washed with 1 ml PBS twice. Antibody-bound peptides were eluted from the beads by heating them at 90°C in 100 μΙ PBS for 5 minutes. This elution step was repeated. 1.2 Mass spectrometry Samples were analyzed by liquid chromatography-mass spectrometry using a Waters nanoACQUITY UPLC System equipped with a C18 nanoACQUITY UPLC BEH 130 column, 75 μιτι x 250mm (186003545) and an LTQ Orbitrap Velos (Thermo Fisher Scientific). Peptides were eluted with a 300nl / min gradient increasing from 3% to 35% acetonitrile over 120 min. Full scan mass spectra were acquired at 60,000 power of resolution between the 400-2000 m / z mass range on the Orbitrap. At each cycle, the twenty most intense peptides were selected for CID MS / MS scans in the linear ion trap with on-instrument fitted nanospray ion source. 1.3 Analysis of peptide amino acid sequences Raw data from the LTQ Orbitrap Velos instrument were processed through the Mascot software (Matrix Science) which employs the Mowse algorithm (Curr Biol. 1993 Jun 1 ;3(6) :327-3) to infer sequences of amino acids from the peak lists by searching against a sequence database consisting of Ensembl (http: / / www.ensembl.org / index.html), IPI (www.ebi.ac.uk / IPI / IPIhuman.html ) and SwissProt (http: / / www.uniprot.org) along with contaminating protein sequences. Criteria for peptide identification included trypsin digestion, up to 2 missing cleavage sites, and various biological and chemical modifications (oxidized methionine, cisterna modification by MMTS or iodoacetamide, and phosphorylation of serine, threonine, and tyrosine). Peptides ranked 1 with an expectation value of 0.05% or less, an ion score of 28 or higher were uploaded to the OGAP database. 1.4 Discrimination of LY75-associated peptides The process to identify LY75 used peptide sequences obtained experimentally by mass spectrometry, as described previously, from naturally occurring human i cci η / ηζηζ / Ε / γ proteins to identify and organize coding exons into the human genome sequence. published. These experimentally determined sequences were compared with the OGAP® database which was compiled by processing and integrating peptide masses, peptide signatures, ESTs and Public Domain Genomic Sequence Data according to as described in the International Patent Application WO2009 / 087462. Results The results of the peptide interaction and precipitation ("polishing down") assay using the LY75_A1 antibody are shown in Table 1 below and in FIGURE 7. The peptides that were identified in both peptide elutions 1a and 1b in the interaction and precipitation assay ("pull down") and in the microarray assay were considered as the most likely candidates to form the epitope. i ccc n / nznz / E / v Table 1 Comparison of peptide microarray and peptide interaction and pull down experiments SEQ ID NO: Peptide Identified by Microarray Assay Peptide Identified by Interaction and Precipitation Assay (“Pulli Down”) Region 1 (aa609-618) - Region 2 (aa651-662) - Region 3 (aa761-780) GWHFYDDR ( 765-772) 41 42 Region 4 (aa883-901) ISEWPIDDHFTYSR(877 to 890) FPVTFGEECLYMSAK(896-910) 43 Region 5 (aa1029-1040) ELTYSNFHPLLVSGR(1030-1044) 44 Region 6 (aa1077-10834) HF108LCK -1091) 45 Region 7 (aa1107-1118) QTLQNASETVK (1099-1109) Region 8 (aa1368-1378) - Region 9 (aa1518-1528) - Region 10 (aa1535-1554) - Table 1 shows that a number of overlapping LY75 peptide regions were identified in both the Peptide Microarray assay and in both elutions 1a and 1b of the peptide "pull down" assay. These regions are considered to be the most likely to contain the epitope recognized by the LY75_A1 antibody since they are bound by LY75_A1 assayed by both techniques employed. Example 26 Synergistic combinations of LY75 DM4 and Venetoclax Several activated B-cell (ABC) diffuse large B-cell lymphoma cell lines DLBCL) (ie U2932, HBL1, OCI-Ly10, TMD8 cell lines) were exposed for 72 hours to increasing doses of LY75_DM4 (ie 18.75 - 37.5 - 75 - 150 - 300 - 600 - 1200 nM) either alone or in combination with increasing doses of Venetoclax (0.64 - 3.2 - 16 - 80 400 - 2000 - 10000 nM). This was followed by an assay of MTT [3-(4,5d¡methylt¡azol¡l-2)-2,5-diphenyltetrazolium bromide]. The Chou-Talalay combination index (C.l.) was estimated using the Synergy R package (Preclinical versus Clinical Drugs Combination Studies. Chou TC. Leuk. Lymphoma. 2008;49(11):2059-2080). This provides a quantitative definition of strong synergy (<0.3), synergy (0.3-0.9), additive effect (0.9-1.1), or antagonism / no benefit (>1.1). Figures 8A-11 show plots of algebraic estimation of OI vs. the Fractional Effect of different doses of LY75_DM4 in combination with Venetoclax on various ABC-DLBCL cell lines. Supporting data is given in Tables 2-5 below. (The “fractional effect” is the effect of one drug dose, or in this case a combination of two different drug doses, on cell viability. See “Drug combination studies and their synergy quantification using the Chou-Talalay method”, Chou TC Cancer Res. 2010 Jan 15;70(2):440-6. Doi: 10.1158 / 0008-5472.CAN-09-1947. Ezine dated 2010 Jan 12; “Evaluation of combination chemotherapy: integration of nonlinear regression, curve shift, isobologram, and combination index analyses", Zhao L1, Wientjes MG, Au JL. Clin Cancer Res. 2004 Dec 1;10(23):7994-8004; and "Computerized quantification of synergism and antagonism of taxol, topotecan, and cisplatin against human teratocarcinoma cell growth: a rational approach to clinical protocol design", Chou TC1, Motzer RJ, Tong Y, Bosl GJ. J Nati Cancer Inst. 1994 Oct 19;86(20):1517 -24). Table 2: Chou-Talalay Combination Index (Cl) of different doses of LY75 DM4 in combination with Venetoclax in the U2932 ABC-DLBCL cell line. No. Rituximab (nM) LY75_DM4 (nM) Cl 1 0.64 18.75 0.228628 2 3.2 18.75 48390.23 3 16 18.75 0.832871 4 80 18.75 48571.11 5 400 18 .75 1.283932 6 2000 18.75 4.300007 7 0.64 37.5 0.20187 8 3.2 37.5 0.158138 9 16 37.5 0.162302 10 80 37.5 0.359423 11 400 37.5 1.063934 12 2000 37.5 4.016023 13 0.64 75 0.240453 14 3.2 75 0.318658 15 16 75 0.269793 16 80 75 0.449203 17 403 194 4 18 2000 75 4.535702 19 0.64 150 0.668392 20 3.2 150 0.503223 21 16 150 0.368141 22 80 150 0.78697 23 400 150 1.229211 7.408 24 2005 2000 300 0.674222 26 3.2 300 0.614852 27 16 300 0.471318 28 80 300 0.612392 29 400 300 1.0508 30 2000 300 2.887408 31 0.64 600 3 8 0.39280 , 269578 33 16 600 0.215265 34 80 600 0.262392 35 400 600 0.482253 36 2000 600 1.556613 37 0.64 1200 0.311401 38 3.2 1200 0.201658 39 16 1200 0.131998 40 80 1200 0.143223 41 400 1200 0.264552 42 2000 1200 0.889985 i ccc ι η / ηζηζ / Ε / γίΛΐ Table 3: Combination index (Ch Chou-Talalavde different doses of LY75 DM4 in combination with Venetoclax in cell line HBL-1 ABC-DLBCL i cci n / nznz / B / v No. Venetoclax (nM) LY75_DM4 (nM) CI 1 0.64 18.75 0.060475 2 3.2 18.75 0.066231 3 16 18.75 0.072936 4 80 18.75 0.103875 5 400 18 .75 0.2431 6 2000 18.75 0.723887 7 10000 18.75 2.513073 8 0.64 37.5 0.2091 9 3.2 37.5 0.126913 10 16 37.5 0.130206 11 80 37.5 0.181304 12 400 37.5 0.257498 13 2000 37.5 0.723106 14 10000 37.5 2.455379 15 0.64 75 0.307332 16 3.2 75 0.251612 75 17 0.235462 18 80 75 0.185182 19 400 75 0.304787 20 2000 75 0.717305 21 10000 75 2.213852 22 0.64 150 0.429262 23 3.2 150 0.324116 24 16 150 0.379524 25 80 150 0.276266 26 400 150 0.341981 27 2000 150 0.641475 28 10000 150 1.688396 29 0.64 300 0.530256 30 3.2 300 0.558872 31 16 300 0.48397 32 80 300 0, 427943 33 400 300 0.411042 34 2000 300 0.581318 35 0.64 600 0.81368 36 3.2 600 0.7166 37 16 600 0.688208 38 80 600 0.539914 39 400 600 0.447228 40 2000 600 , 576687 41 10000 600 0.927968 42 0.64 1200 1,462271 43 3.2 1200 1,463631 44 16 1200 1.240995 45 80 1200 0.962969 46 400 1200 0.699419 47 2000 1200 0.834858 48 10000 1200 1.20449 Table 4: Combination index (Ch Chou-Talalav of different doses of LY75 DM4 in combination with Venetoclax in the OCI-LY10 ABC-DLBCL cell line No. Venetoclax (nM) LY75_DM4 (nM) Cl 1 0.64 18.75 0.358713 2 3.2 18.75 0.390664 3 16 18.75 0.528223 4 80 18.75 0.519535 5 400 18 .75 0.48347 6 2000 18.75 0.449909 7 0.64 37.5 0.76338 8 3.2 37.5 0.792829 9 16 37.5 0.863246 10 80 37.5 0.849432 11 400 37.5 0.842251 12 2000 37.5 0.83696 13 0.64 75 1.620332 14 3.2 75 1.497024 15 16 75 1.52695 16 80 75 1.247205 17 400 75 1.03465 18 2000 75 0.679064 19 0.64 150 2.591237 20 3.2 150 2.543499 21 16 150 2.319816 22 80 720 250 9 150 .529779 24 2000 150 1.245879 i ccci η / ηζηζ / Ε / γ Table 5: Chou-Talalav Combination Index (Cl) of different doses of LY75 DM4 in combination with Venetoclax in the TMD8 ABC-DLBCL cell line No. Venetoclax (nM) LY75_DM4 (nM) Cl 1 0.64 18.75 3.857478 2 3.2 18.75 0.280543 3 16 18.75 0.384029 4 80 18.75 0.317572 5 400 18 .75 0.746108 6 2000 18.75 1.517033 7 10000 18.75 5.015455 8 0.64 37.5 0.563791 9 3.2 37.5 0.501728 10 16 37.5 0.518688 11 80 37.5 0.54784 12 400 37.5 0.769738 13 2000 37.5 1.419712 14 10000 37.5 5.250996 15 0.64 75 1.002662 16 3.2 75 0.925877 75 16 0.941806 18 80 75 0.952971 19 400 75 1.073273 20 2000 75 1.592762 21 10000 75 4.559974 22 0.64 150 1.564785 23 3.2 150 1.540005 24 16 150 1.522806 25 80 150 1.396608 26 400 150 1.273743 27 2000 150 1.376175 28 10000 150 0.217978 i ccci η / ηζηζ / Ε / γ INFORMATION ABOUT SEQUENCE LISTING: SEQ ID No Descripción Secuencia 1 A1VH aa EVQLVESGGGLVKPGGSLRLSCAASGFTYSNAWMSWVRQ APGKGLEWVGRIKSKTDGGTTDYAAPVQGRFTISRDDSKN TLYLQMNSLKTEDTAVYYCTIFGVVSFDYWGQGTLVTVSS 2 A1VL aa DVQMTQSPSSLSASVGDRVTITCRASQSISDYLSWYQQRP GKAPNLLIYAASNLKTGVPSRFSGSGSGTDFTLTISTLQPED FATYYCQQSYRSPWTFGQGTKVEIKR 3 A1VH nt gaggtgcagctggtggagtctgggggaggcttggtaaagccgggggggtccctta gactctcctgtgcagcctctggcttcacttacagtaacgcctggatgagctgggtccg ccaggctccagggaaggggctggagtgggttggccgtattaaaagcaaaactgat ggtgggacaacagactacgctgcacccgtgcaaggcagattcaccatctcaagag atgattcaaaaaacacgctgtatctgcaaatgaacagcctgaaaaccgaggacac agccgtgtattactgtacgatttttggagtggttagctttgactactggggccagggaac cctg g tcaccg tctcctca 4 A1VL nt gacgtccagatgacccagtctccatcctccctgtctgcatctgttggagacagagtca ccatcacttgccgggcaagtcagagcattagcgactatttaagttggtatcagcaga g accag g g aaagcccctaacctcctg atctatgctg catccaatttaaag actg gg g tcccatcaag g ttcag tg gcag tg g atctg g g acag atttcactctcaccatcagcac tctgcaacctg aag attttgcaacg tactactg tcaacag ag ttacag g tccccg tg g acg t tcg gccaag g g accaagg tg g aaatcaaacg a 5 A1VHCDR 1 aa NAWMS 6 A1VHCDR 2 aa RIKSKTDGGTTDYAAPVQG 7 A1VHCDR 3 aa FGVVSFDY 8 A1VLCDR1 RASQSISDYLS aa 9 A1VLCDR2 aa AASNLKT 10 A1VLCDR3 aa QQSYRSPWT 11 VH3|3- 15 / D4|411 EVQLVESGGGLVKPGGSLRLSCAASGFTFSNAWMSWVRQ APGKGLEWVGRIKSKTDGGTTDYAAPVKGRFTISRDDSKNT LYLQMNSLKTEDTAVYYCI I I I VT 12 JH4 YFDYWGQGTLVTVSS 13 012 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPG KAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDF ATYYCQQSYS 14 JK1 WTFGQGTKVEIKR 15 LY75 (DEC- 205) MRTGWATPRRPAGLLMLLFWFFDLAEPSGRAANDPFTIVH GNTGKCIKPVYGWIVADDCDETEDKLWKWVSQHRLFHLHS QKCLGLDITKSVNELRMFSCDSSAMLWWKCEHHSLYGAAR YRLALKDGHGTAISNASDVWKKGGSEESLCDQPYHEIYTRD GNSYGRPCEFPFLIDGTWHHDCILDEDHSGPWCATTLNYE YDRKWGICLKPENGCEDNWEKNEQFGSCYQFNTQTALSW KEAYVSCQNQGADLLSINSAAELTYLKEKEGIAKIFWIGLNQ LYSARGWEWSDHKPLNFLNWDPDRPSAPTIGGSSCARMD AESGLWQSFSCEAQLPYVCRKPLNNTVELTDVWTYSDTRC DAGWLPNNGFCYLLVNESNSWDKAHAKCKAFSSDLISIHSL ADVEVVVTKLHNEDIKEEVWIGLKNINIPTLFQWSDGTEVTL TYWDENEPNVPYNKTPNCVSYLGELGQWKVQSCEEKLKY VCKRKGEKLNDASSDKMCPPDEGWKRHGETCYKIYEDEVP FGTNCNLTITSRFEQEYLNDLMKKYDKSLRKYFWTGLRDVD SCGEYNWATVGGRRRAVTFSNWNFLEPASPGGCVAMSTG KSVGKWEVKDCRSFKALSICKKMSGPLGPEEASPK PDDPC PEGWQSFPASLSCYKVFHAERIVRKRNWEEAERFCQALGA HLSSFSHVDEIKEFLHFLTDQFSGQHWLWIGLNKRSPDLQG SWQWSDRTPVSTHMPNEFQQDYDIRDCAAVKVFHRPWRR GWHFYDDREFIYLRPFACDTKLEWVCQIPKGRTPKTPDWY NPDRAGIHGPPLIIEGSEYWFVADLHLNYEEAVLYCASNHSF LATITSFVGLKAIKNKIANISGDGQKWWIRISEWPIDDHFTYS RYPWHRFPVTFGEECLYMSAKTWLIDLGKPTDCSTKLPFIC i ccci η / ηζηζ / Ε / γ EKYNVSSLEKYSPDSAAKVQCSEQWIPFQNKCFLKIKPVSL TFSQASDTCHSYGGTLPSVLSQIEQDFITSLLPDMEATLWIG LRWTAYEKINKWTDNRELTYSNFHPLLVSGRLRIPENFFEE ESRYHCALILNLQKSPFTGTWNFTSCSERHFVSLCQKYSEV KSRQTLQNASETVKYLNNLYKIIPKTLTWHSAKRECLKSNM QLVSITDPYQQAFLSVQALLHNSSLWIGLFSQDDELNFGWS DGKRLHFSRWAETNGQLEDCVVLDTDGFWKTVDCNDNQP GAICYYSGNETEKEVKPVDSVKCPSPVLNTPWIPFQNCCYN FIITKNRHMATTQDEVHTKCQKLNPKSHILSIRDEKENNFVLE QLLYFNYMASWVMLGITYRNKSLMWFDKTPLSYTHWRAGR PTIKNEKFLAGLSTDGFWDIQTFKVIEEAVYFHQHSILACKIE MVDYKEEYNTTLPQFMPYEDGIYSVIQKKVTWYEALNMCS QSGGHLASVHNQNGQLFLEDIVKRDGFPLWVGLSSHDGSE SSFEWSDGSTFDYIPWKGQTSPGNCVLLDPKGTWKHEKC NSVKDGAICYKPTKSKKLSRLTYSSRCPAAKENGSRWIQYK GHCYKSDQALHSFSEAKKLCSKHDHSATIVSIKDEDENKFV SRLMRENNNITMRVWLGLSQHSVDQSWSWLDGSEVTFVK WENKSKSGVGRCSMLIASNETWKKVECEHGFGRVVCKVP LGPDYTAIAIIVATLSILVLMGGLIWFLFQRHRLHLAGFSSVR YAQGVNEDEIMLPSFHD 16 A1VHFR1 EVQLVESGGGLVKPGGSLRLSCAASGFTYS 17 A1VHFR2 WVRQAPGKGLEWVG 18 A1VHFR3 RFTISRDDSKNTLYLQMNSLKTEDTAVYYCTI 19 A1VHFR4 WGQGTLVTVSS 20 A1VLFR1 DVQMTQSPSSLSASVGDRVTITC 21 A1VLFR2 WYQQRPG KAPNLLIY 22 A1VLFR3 GVPSRFSGSGSGTDFTLTISTLQPEDFATYYC 23 A1VLFR4 FGQGTKVEIKR 24 LY75 609-618 WEVKDCRSFK 25 LY75 651-662 PASLSCYKVFHA 26 LY75 761 -780 PWRRGWHFYDDREFIYLRPF 27 LY75 883-901 DDHFTYSRYPWHRFPVTFG 28 LY75 1029- 1040 RELTYSNFHPLL 29 LY75 1077- 1093 FTSCS E R H FVS LCQKYS i ccci η / ηζηζ / Ε / γ 30 LY75 1107- 1118 TVKYLNNLYKII 31 LY75 1368- 1378 EAVYFHQHSIL 32 LY75 1518- 1528 KKLSRLTYSSC 33 LY75 1535- 1554 NGSRWIQYKGHCYKSDQALH 34 LY75 877-901 ISEWPIDDHFTYSRYPWHRFPVTFG 35 LY75 1099- 1118 QTLQNASETVKYLNNLYKII 36 LY75 883-892 DDHFTYSRYP 37 LY75 1077- 1091 FTSCSERHFVSLCQK 38 A1_H (amino acid) MEWSWVFLFFLSVTTGVHSEVQLVESGGGLVKPGGSLRLS CAASGFTYSNAWMSWVRQAPGKGLEWVGRIKSKT DGGTTDYAAPVQGRFTISRDDSKNTLYLQMNSLKTEDTAVY YCTIFGVVSFDYWGQGTLVTVSSASTKGPSVFPLAP SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK 39 A1 L (amino acid) MSVPTQVLGLLLLWLTDARCDVQMTQSPSSLSASVGDRVTI TCRASQSISDYLSWYQQRPGKAPNLLIYAASN LKTGVPSRFSGSGSGTDFTLTISTLQPEDFATYYCQQSYRS PWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGT ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYS LSSTLTLSKADYEKHKVYACEVTHQGLS SPVTKSFNRGEC 40 (765-772) GWHFYDDR 41 (877 to 890) ISEWPIDDHFTYSR i ccci η / ηζηζ / Ε / γ 42 (896-910) FPVTFGEECLYMSAK 43 (1030-1044) ELTYSNFHPLLVSGR 44 (1084-1091) HFVSLCQK 45 (1099-1109) QTLQNASETVK 46 Linker Gly-Phe-Leu-Gly Free text of the sequence listing: SEQ ID NO: 38 <223> A1 heavy chain SEQ ID NO: 39 <223> A1 heavy chain SEQ ID NO: 46 <223> Ligator SEQ ID NOs: 47-157 <223> Peptide SEQ ID NOs: 159-201 <223> Peptide i cci η / ηζηζ / Ε / γ NOVELTY OF THE INVENTION Having described the present invention as above, it is considered a novelty and, therefore, what is contained in the following is claimed as property:

Claims

1. A pharmaceutical combination, characterized in that it comprises: (A) an anti-LY75 antibody, or an antigen-binding portion thereof, which competes for binding to LY75 with an antibody comprising a heavy-chain variable region comprising the amino acid sequence set out in SEQ ID NO: 1, and a light-chain variable region comprising the amino acid sequence set out in SEQ ID NO: 2; or an anti-LY75 antibody, or an antigen-binding portion thereof, said antibody comprising: (a) a heavy-chain variable region comprising: (i) a first vhCDR comprising SEQ ID NO: 5; (ii) a second vhCDR comprising SEQ ID NO: 6; (iii) a third vhCDR comprising SEQ ID NO: 7; and (b) a light-chain variable region comprising: (i) a first vICDR comprising SEQ ID NO: 8; (ii) a second vICDR comprising SEQ ID NO: 9; and iii) a third vICDR comprising SEQ ID NO: 10;optionally wherein any one or more of the SEQ ID NOs listed above independently comprise one, two, three, four or five amino acid substitutions, additions or deletions; and (B) Venetoclax or a pharmaceutically acceptable salt thereof wherein the pharmaceutical combination is in the form of a combination preparation for simultaneous, separate or sequential use, preferably for the treatment of cancer.

2. The pharmaceutical combination according to claim 1, characterized in that any one or more of the SEQ ID NO: 5-10 independently comprise one, two, three, four or five preservative amino acid substitutions.

3. The pharmaceutical combination according to claim 2, characterized in that any one or more of the SEQ ID NO: 5-10 independently comprise one or two preservative amino acid substitutions.

4. The pharmaceutical combination according to any one of claims 1 to 3, characterized in that the anti-LY75 antibody or an antigen-binding portion thereof comprises: (i) a heavy chain variable region having at least 80%, 85%, 90%, 95%, 99% or 100% amino acid sequence identity with SEQ ID NO: 1; and (ii) a light chain variable region having at least 80%, 85%, 90%, 95%, 99% or 100% amino acid sequence identity with SEQ ID NO:

2.

5. The pharmaceutical combination according to any one of claims 1 to 4, characterized in that the anti-LY75 antibody comprises: (i) a heavy chain having at least 80%, 85%, 90%, 95%, 99% or 100% amino acid sequence identity with SEQ ID NO: 38; and (II) a light chain having at least 80%, 85%, 90%, 95%, 99% or 100% amino acid sequence identity with SEQ ID NO:

39.

6. The pharmaceutical combination according to any of claims 1 to 5, characterized in that the anti-LY75 antibody is a human monoclonal IgG1 antibody.

7. The pharmaceutical combination according to any of claims 1 to 6, characterized in that the anti-LY75 antibody or an antigen-binding portion thereof further comprises a covalently bound portion.

8. The pharmaceutical combination according to claim 7, characterized in that said portion is a drug.

9. The pharmaceutical combination according to claim 8, characterized in that said drug is a maitansinoid or a derivative thereof.

10. The pharmaceutical combination according to claim 9, characterized in that said drug is DM4 or DM1.

11. The pharmaceutical combination according to any of claims 1 to 10, characterized in that (A) and / or (B) further comprise one or more pharmaceutically acceptable diluents, excipients or carriers.

12. The pharmaceutical combination according to any of claims 1 to 11, characterized in that the pharmaceutical combination is in the form of a combined preparation for simultaneous, separate or sequential use for the treatment of diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin lymphoma.

13. The pharmaceutical combination according to any of claims 1 to 12, further characterized in that it comprises instructions for treating cancer in a patient requiring such treatment by administering (A) and (B) to the patient.

14. A method for treating cancer in a patient, characterized in that it comprises administering simultaneously, sequentially or separately to a patient in need therapeutically effective quantities of components (A) and (B) of a pharmaceutical combination as defined in any of claims 1 to 11.

15. The method according to claim 14, characterized in that the anti-LY75 antibody or an antigen-binding portion thereof is internalized by a cell expressing LY75.

16. The method according to claim 14 or 15, characterized in that the anti-LY75 antibody or the antigen-binding portion thereof comprises a covalently bound conjugated drug.

17. The method according to claim 16, characterized in that the covalently bound conjugated drug is a maitansinoid, preferably DM4.

18. The method according to any of claims 14 to 17, characterized in that the cancer is diffuse large B cell lymphoma (DLBCL) or non-Hodgkin lymphoma.

19. A pharmaceutical combination according to any of claims 1 to 11, characterized in that it is for use in the treatment of cancer, wherein components (A) and (B) are administered simultaneously, separately or sequentially to a patient for the treatment of cancer.

20. The pharmaceutical combination for use according to claim 19, characterized in that the anti-LY75 antibody or an antigen-binding portion thereof is internalized by a cell expressing LY75.

21. The pharmaceutical combination for use according to claim 19 or 20, characterized in that the anti-LY75 antibody or an antigen-binding portion thereof comprises a covalently bound conjugated drug.

22. The pharmaceutical combination for use according to any one of claims 19 to 21, characterized in that the covalently bound conjugated drug is a maitansinoid, preferably DM4.

23. The pharmaceutical combination for use according to any one of claims 19 to 22, characterized in that the cancer is diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin lymphoma.

24. Use of components (A) and (B) of the pharmaceutical combination defined in any of claims 1 to 15 in the preparation of a pharmaceutical combination for simultaneous, separate or sequential use for the treatment of cancer.

25. Use according to claim 24, wherein the anti-LY75 antibody or an antigen-binding portion thereof is internalized by a cell expressing LY75.

26. Use according to claim 24 or 25, wherein the anti-LY75 antibody or an antigen-binding portion thereof comprises a covalently bound drug conjugate.

27. Use according to claim 26, wherein the covalently bound conjugated drug is a maitansinoid, preferably DM4.

28. Use in accordance with any one of claims 24 to 27, wherein the cancer is diffuse large B-cell lymphoma (DLBCL) or non-Hodgkin lymphoma.

29. A pharmaceutical combination according to any one of claims 1 to 11, characterized in that it is for use in therapy or for use as a medicament.