Influence of tumor vaccines on graft versus tumor activity and graft versus host disease in allogeneic bone marrow transplantation

Powerful immunologically-mediated antitumor efforts can be observed in allogeneic hematopoietic stem cell transplantation. In the absence of specific immune interventions, this graft versus tumor effect is closely associated with graft versus host disease. In the work summarized here, the influence of cellular tumor vaccines on graft versus tumor activity and graft versus host disease is examined in a murine model of MHC-matched, minor histocompatibility antigen-mismatched bone marrow transplantation. The experiments have generated the following conclusions. First, complex cellular vaccines, which include recipient minor histocompatibility antigens, when administered to allogeneic donors generate powerful graft versus tumor effects but also induce unacceptable exacerbations of graft versus host disease. Second, cellular tumor vaccines, which contain recipient minor histocompatibility antigens, can be administered to transplant recipients after transplant without significant exacerbation of GVHD and with retention of clinically significant graft versus tumor effects. Third, immunization of donors with molecularly defined tumor-associated antigens, which are not recipient minor histocompatibility antigens, can be coupled with post-transplant immunization of recipients with cellular vaccines without exacerbation of GVHD.