CELLULAR IMMUNOTHERAPY AND AUTOLOGOUS TRANSPLANTATION FOR HEMATOLOGICMALIGNANCY

The success of allogeneic transplantation is in part due to the immuno therapeutic effect mediated by the graft. Autologous transplantation i s hampered by the absence of this effect, leading to a higher relapse rate. We have conducted a series of studies designed to augment the im munologic activity of the graft after autologous transplant with a vie w towards introducing an autologous graft-versus-tumor effect that cou ld decrease the rare of relapse after autologous transplant. These stu dies have included IL-2 activation of marrow followed by post-transpla nt infusional IL-2, the development of a never protocol for the genera tion of highly efficient cytotoxic effector cells, termed cycokine-ind uced killer (CIK) cells, with broad and potent antitumor activity. In order to determine the potential for generating peptide-specific cytol ytic T cells, studies have been conducted upon transducing antigen-pre senting cells (APC) with AAV vector-mediated gene transfer, a vector c apable of transducing non-proliferating target cells. Transduction of human monocytes and macrophages resulted in high expression of the tra nsduced gene. This latter study forms the basis for determining whethe r genetic modification of APC can potentiate specific immune responses to tumor-specific gene products. Taken together, these strategies wil l hopefully increase the therapeutic efficacy of autologous transplant ation.