Characterization of a novel anti-CD20 StradobodyTM with potent in vitro anti-tumor activity (TUM7P.935)

Despite the efficacy of anti-CD20 mAb in the treatment of B-cell malignancies, a proportion of patients are non-responsive or relapse after mAb therapy. Therefore, developing more effective mAbs represents a major area of interest. In this study, we assessed a novel anti-CD20 antibody (stradobody TM from Gliknik Inc.) consisting of an unmodified Fab sequence and a multimerized Fc domain. In vitro, the anti-CD20 stradobody TM mediates significantly enhanced inhibition of cell proliferation on select B lymphoma cell lines relative to the unmodified anti-CD20 mAb. In addition, B lymphoma cell lines exhibit increased susceptibility to Complement Dependent cytotoxicity in the presence of a low concentration of the anti-CD20 stradobody TM . However, anti-CD20 stradobody TM did not elicit enhanced anti-tumor efficacy in vivo in a Raji-scid xenograft model, in comparison with unmodified anti-CD20 mAb. This discrepancy of in vitro and in vivo anti-tumor efficacy of anti-CD20 stradobody TM might be attributable to less avidity of the modified human Fc domain to the murine receptors compared with human receptors and highlights the challenges with validating novel targeted mAb therapeutics in vivo.