Abstract
BackgroundIn vivo use of monoclonal antibodies has become routine clinical practice in the treatment of human cancer. CD38 is an attractive target, because it has double roles, as a receptor and an ectoenzyme. Daratumumab, an anti-CD38 antibody, is currently in the clinical trials for multiple myeloma.ResultsHere we obtained a humanized anti-CD38 antibody, SG003, using SDR-grafting method. SG003 possessed stronger antigen binding activity than Daratumumab, and its epitope was far from that of Daratumumab, an anti-CD38 antibody currently in the clinical trials for multiple myeloma; besides, SG003 showed enhanced antibody-dependent cell-mediated cytotoxicity function and in vivo inhibitory efficacy of tumor growth in xenograft mice model.ConclusionSG003 seemed to be a good option to improve the curative effect of CD38-related cancers.
Highlights
In vivo use of monoclonal antibodies has become routine clinical practice in the treatment of human cancer
3G3 can kill the lymphocytes by Antibody-dependent cell cytotoxicity (ADCC) function 3G3 was screened out using classical hybridoma technology
Dosage ELISA showed the EC50 value of SG003 as 0.0498 μg/mL to bind the coated sCD38, which is ~ 6 times stronger than Daratumumab (EC50 = 0.3005 μg/mL); the maximum OD value of SG003 was obviously higher than Daratumumab (Fig. 3a, 2.4 of SG003 V.S. 1.5 of Daratumumab); flow cytometry assays showed that SG003 had stronger cell surface CD38-binding activity than Daratumumab in either Raji (Fig. 3b) or Daudi (Fig. 3c) cells
Summary
In vivo use of monoclonal antibodies has become routine clinical practice in the treatment of human cancer. SG003 possessed stronger antigen binding activity than Daratumumab, and its epitope was far from that of Daratumumab, an anti-CD38 antibody currently in the clinical trials for multiple myeloma; besides, SG003 showed enhanced antibody-dependent cell-mediated cytotoxicity function and in vivo inhibitory efficacy of tumor growth in xenograft mice model. It’s expressed highly in committed progenitor bone marrow (early BM cells are CD38 negative), and B lymphocytes in germinal centers. It is expressed at low levels on lymphoid and myeloid cells and in some tissues of non-hematopoietic origin [1]; besides, many studies reported that myeloma
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