Our group focuses on using preclinical mouse models of allogeneic blood and marrow transplant to cure pediatric leukemias and solid tumors with tumor-directed immunotherapies such as dendritic cell vaccines, natural killer (NK) cell and T cell-based infusions.
Dr. Capitini has previously demonstrated that even subclinical graft-versus-host-disease (GVHD) can have deleterious effects on the efficacy of tumor vaccines as well as promote tumor growth after allogeneic bone marrow transplant (alloBMT). He also showed a novel approach of modulating GVHD with preservation of anti-tumor responses by T cells and vaccine through usage of bone marrow deficient in gamma interferon receptor signaling. By using this platform, one can give high doses of T cells without inducing GVHD.
Ongoing studies in this laboratory are exploring the mechanism of this effect in donor-derived antigen presenting cells. He is also exploring the biology of expanding allogeneic NK cells ex vivo for treating pediatric tumors after alloBMT. Because of recent efforts to bring cytokines like IL-15 and IL-21 to the clinic, artificial antigen presenting cells that express costimulatory molecules are being combined with these cytokines to stimulate NK cell proliferation and activation ex vivo. Ongoing work is comparing NK cells expanded with a variety of agents against several pediatric tumors in the alloBMT setting.