Anti-CD37 mAb (BI 836826)

CD37 is a leukocyte-specific cell surface protein, expressed on B and T lymphocytes, monocytes, macrophages, neutrophils and dendritic cells.1 High levels of CD37 are found on mature B-cell leukaemia and lymphoma cells,2,3 which makes it a potential target for immunotherapy using monoclonal antibodies (mAb).4

Boehringer Ingelheim is currently investigating BI 836826, a chimeric IgG1 anti-CD37 mAb. BI836826 has been engineered for improved antibody-dependent cellular cytotoxicity (ADCC) by replacing two amino acids in the Fc region to increase binding affinity to FcyRIIIa.4 The compound induces cell death by two different mechanisms and displays intrinsic pro-apoptotic activity.4 In vitro studies in Ramos and chronic lymphocytic leukaemia (CLL) cells indicate that BI 836826 seems to have superior ADCC and apoptotic activity compared with the anti-CD20 mAb rituximab. BI 836826 shows efficient depletion of CLL cells in whole blood samples ex vivo, which also seems to be superior to rituximab.5 Combination of BI 836826 with chemotherapy or rituximab resulted in improved efficacy against lymphoma cells in vitro as well as in a xenograft model of human lymphoma in mice.5

BI 836826 is currently being investigated in Phase I studies with patients with malignancies of the lymphoid system, CLL and non-Hodgkin’s lymphoma.

References: 
  1. van Spriel AB, Puls KL, Sofi M, et al. A regulatory role for CD37 in T cell proliferation. J Immunol 2004;172(5):2953-2961.
  2. Barrena S, Almeida J, Yunta M, et al. Aberrant expression of tetraspanin molecules in B-cell chronic lymphoproliferative disorders and its correlation with normal B-cell maturation. Leukemia 2005;19(8):1376-1383.
  3. Belov L, de la Vega O, dos Remedios CG, Mulligan SP, Christopherson RI. Immunophenotyping of leukemias using a cluster of differentiation antibody microarray. Cancer Res 2001;61(11):4483-4489.
  4. Heider KH, Kiefer K, Zenz T, et al. A novel Fc-engineered monoclonal antibody to CD37 with enhanced ADCC and high proapoptotic activity for treatment of B-cell malignancies. Blood 2011;118(15):4159-4168.
  5. Krause G, Baki I, Kerwien S, et al. Cytotoxicity of the CD37 antibody BI 836826 against chronic lymphocytic leukaemia cells in combination with chemotherapeutic agents or PI3K inhibitors. Br J Haematol 2016;173(5):791–794.
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