CD40-ACTIVATED HUMAN B-CELLS - AN ALTERNATIVE SOURCE OF HIGHLY EFFICIENT ANTIGEN-PRESENTING CELLS TO GENERATE AUTOLOGOUS ANTIGEN-SPECIFIC T-CELLS FOR ADOPTIVE IMMUNOTHERAPY

Multiple clinical trials have shown the efficacy of adoptively transfe rred allogeneic antigen-specific T cells for the treatment of viral in fections and relapsed hematologic malignancies. In contrast, the thera peutic potential of autologous antigen-specific T cells has yet to be established since it has been technically difficult to generate suffic ient numbers of these T cells, ex vivo. A major obstacle to the succes s of this objective derives from our inability to simply and rapidly i solate and/or expand large numbers of highly efficient antigen present ing cells (APCs) for repetitive stimulations of antigen-specific T cel ls in vitro. We show that autologous CD40-activated B cells represent a readily available source of highly efficient APC that appear to have several important advantages over other APCs for ex vivo T cell expan sion including: (a) methodological simplicity necessary to generate co ntinuously large numbers of APCs from just 50 cm(3) of peripheral bloo d without loss of APC function; (b) capacity to induce high peak T cel l proliferation and interferon-gamma production without IL-10 producti on; (c) ease in cryopreservation; and (d) markedly reduced cost. We, t herefore, contend that CD40-activated B cells are an alternative sourc e of highly efficient APCs with which to generate antigen-specific T c ells ex vivo for autologous adoptive immunotherapy.