• Multiple Myeloma

I am a board-certified hematologist and stem cell transplant physician with more than 25 years of experience in the care of patients with hematopoietic neoplasms and benign hematologic disorders. In relation to the current grant, I have conducted translational research focused on the use of costimulated autologous T cells and vaccines to enhance immune recovery after autologous stem cell transplants for hematologic malignancies. Between 1998 and 2015, I have directed 6 major clinical trials of adoptive T-cell therapy that have enrolled more than 150 patients. Our group was among the first to show that combination immunotherapy using vaccine-primed and ex vivo costimulated autologous T cells could induce robust vaccine-specific immune responses early after autologous stem cell transplantation (ASCT) for myeloma.

We also demonstrated for the first time that early adoptive transfers of costimulated T cells could induce robust T-cell recovery posttransplant and elicit graft-versus-host disease–like reactions in the autologous transplant setting. In recent work, we described a novel combination of activated T cells, tumor antigen vaccine (MAGE-A3), and a novel vaccine adjuvant (Poly-ICLC), which generated a high frequency of tumor antigen vaccine–specific T-cell responses (>70 percent) after ASCT for myeloma.

In another major clinical trial, we have utilized high-affinity T-cell receptor (TCR) gene-modified T cells for adoptive cellular therapy after ASCT for myeloma. The engineered T cells expanded, persisted, trafficked to marrow, and exhibited cytotoxic function. These clinical trials have provided a new avenue for rapid reconstitution of T-cell–mediated immunity following blood/marrow transplantation and laid the groundwork for the development of effective cellular immunotherapy of myeloma.