Redesigning allogeneic bone marrow transplantation as immunotherapy for solid cancers
Although only recently cancer immunotherapy has received great attention with the development of checkpoint inhibitors, cancer immunotherapy has been around for more than 3 decades. In fact, allogeneic bone marrow transplantation (alloBMT) was the first form of cancer immunotherapy as its anti-tumor effects are strictly dependent on immune-mediated anti-tumor reactivity mediated by immune cells contained in the transplanted graft or derived from the developing immune system (graft-versus-tumor effect, GvT). In this project, we aim to redesign alloBMT as immunotherapy for solid cancers using 2 approaches. First is the development of recipient lymphocyte infusion (infusion of host immune cells) as adoptive cell therapy following alloBMT to allow for potent GvT effects without risk for graftversus-host disease (GvHD). Myeloid-derived suppressor cells impede RLImediated anti-tumor effects and in this project, we will study the mechanisms underlying this effect, establish approaches to overcome it and extend our study to pediatric patients with solid tumors. The second approach is the develop T celldepleted alloBMT in the treatment of solid tumors as we recently established that T cell-depletion results in the absence GvHD and potent GvT effects in a murine melanoma model. This effect seems to be dependent tumor-associated macrophages. In this project, we will examine the underlying mechanisms of these phenomena and extend it to other tumor models.