Cooperation of the proapoptotic receptor agonist rhApo2L/TRAIL with the CD20 antibody rituximab against non-Hodgkin lymphoma xenografts

摘要: Recombinant human rhApo2L/TRAIL selectively stimulates apoptosis in various cancer cells through its receptors DR4 and DR5, is currently clinical trials. Preclinical studies have established antitumor activity of models epithelial cancers; however, efficacy non-Hodgkin lymphoma (NHL) not well studied. Of 7 NHL cell lines tested vitro, stimulated BJAB, Ramos RA1, DoHH-2 cells. Rituximab, a CD20 antibody used to treat certain types NHL, augmented rhApo2L/TRAIL-induced caspase activation RA1 DoHH2 but BJAB or SC-1 cells, modulation intrinsic rather than extrinsic signaling. In vivo, rituximab cooperated attenuate reverse growth tumor xenografts all 4 these lines. Depletion natural killer (NK) serum complement substantially reduced combined against tumors, suggesting involvement antibody-dependent cell- complement-mediated cytotoxicity. Both agents exhibited greater disseminated subcutaneous xenografts, worked together inhibit abolish tumors increase survival. Moreover, helped circumvent acquired resistance variant. These findings provide strong rationale for investigation combination with as novel strategy therapy.