Anti-clecl1 antibodies for treatment and prognosis of chronic lymphocytic leukemia and other diseases

A method for predicting disease relapse in a patient or for measuring residual disease in a patient, the method comprising analyzing a sample from blood, bone marrow or a lymph node of a patient who is or has been treated for the disease for the presence of CLECL1+ cells,

• wherein the presence of CLECL1+ cells in the patient's sample is detected using a monoclonal antibody to CLECL1 or antigen-binding fragment thereof,
• wherein appearance of CLECL1+ cells in the sample is indicative of development of resistance to therapy or presence of residual disease, and
• wherein the disease is one or more of chronic lymphocytic leukemia (CLL), a B-cell lymphoproliferative disorder, follicular lymphoma, Burkitt's lymphoma, mantle cell lymphoma, marginal zone lymphoma, Waldenstrom's macroglobulinemia, diffuse large B-cell lymphoma, multiple myeloma;
• acute leukemia, acute lymphocytic leukemia, acute myeloid leukemia, acute myelomonocytic leukemia, an autoimmune condition where the production of antibodies by B cells or their derivatives are pathogenic, systemic lupus erythematosus (SLE), rheumatoid arthritis, graft versus host disease (GvHD), multiple sclerosis, a disease where the generation of a Th2 microenvironment is detrimental, atopic dermatitis, asthma, hyper-IgE syndrome, Langerhans cell histiocytosis, a disease where cells of the granulocyte lineage are pathogenic, myelodysplastic syndrome (MDS), and chronic myelogenous leukemia (CML).

A monoclonal antibody to CLECL1 comprising:

• a) a heavy chain complementarity determining region (CDR) comprising SEQ ID NO:4, EVQLQQSGAELVRSGASVKLSCTTSGFNIKDFYIHWVRQRPEQGLEWIGWIDPKNDDTE YAPRFQGKATVTADTSSNTAYLHLSGLTSEDTAVYYCNGRYPTMDFWGQGTSVT, and a light chain CDR comprising SEQ ID NO:5, EIVLTQSPITMTTSPGEKITITCSASSSISSHYLHWYQQKPGFSPKLLIYRASNLASGVPTRF SGSGSGTSYSLTIDTMEAEDVATYFCQQGSSLPLTFGAGTKLELK;
• or
• b) a heavy chain CDR comprising SEQ ID NO:6, EVQLQQSGTVLVRSGASVKLSCTASGFNIKEYYIHWVKQRPEQGLEWIAWIDLENGESE YAPKFQGKATLTADTSSNTAYLQLSGLTSEDTAVYYCNAFHGNYAHNYAIDYWGQGTS VTVSQ, and a light chain CDR comprising SEQ ID NO:7, DIVMSQSPSSLAVSAGEKVTMTCKSSQSLLNSRTRKNYLAWYQQKPGQSPKLLIYWAST RKSGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCKQSYNLRTFGGGTKLEIK;
• or
• c) a heavy chain CDR comprising SEQ ID NO:8, EVKLLESGGGLVQPGGSLKLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTIN YTPSLKDKFIISRDNAKNTLYLQMSKVRSEDTALYYCARRGGYFAYWGQGTLVTVSA, and a light chain CDR comprising SEQ ID NO:9, DIVLTQSPASLAVSLGQRATISYRASKSVSTSGYSYMHWNQQKPGQPPRLLIYLVSNLES GVPARFSGSGSGTDFTLNIHPVEEEDAATYYCQHIRELTRSEGGPSWK.