A humanizedaAnti-CD40 monoclonal antibody (SGN-40) demonstrates antitumor activity in non-Hodgkin’s lymphoma: Initiation of a phase I clinical trial

6572 Background: CD40, a member of the Tumor Necrosis Factor (TNF) receptor family, is expressed on the cell surface of normal B lymphocytes, their progenitors, and B cell malignancies, including both indolent and aggressive forms of non-Hodgkin’s lymphoma (NHL). Because this represents an attractive target for immunotherapy, a humanized monoclonal anti-CD40 antibody (SGN-40) has been developed and tested in preclinical models. Methods: SGN-40-dependent proliferation and cell killing were tested in vitro using normal B cells and malignant lymphoma cell lines. Antibody-dependent cell-mediated cytotoxicity (ADCC) was assessed by adding peripheral blood mononuclear cells or purified NK cells to malignant cell lines in the presence of SGN-40. In vivo activity of SGN-40 was determined by xenograft models in SCID mice. Results: Although SGN-40 induces proliferation of normal B cells when crosslinked and exposed to exogenous IL-4, there was dose-dependent B cell depletion and no evidence of activation in non-hum...