The goal of my research is to develop effective immunotherapy for pediatric cancer. We build upon expertise in the biology of T cell homeostasis to enhance immune responses to tumor-associated antigens following T cell depleting chemotherapy and to amplify immune responses to tumor antigens in…
more lymphoreplete hosts. Through murine, primate and human studies, we have identified IL7 as a physiological modulator of T cell homeostasis, and a potent vaccine adjuvant. On this basis, we are currently participating in the clinical development of rhIL7. We also undertake clinical studies of tumor immunotherapy and immune reconstitution in patients with pediatric solid tumors. This work has demonstrated that age-associated thymic involution substantially limits immune reconstitution in most clinical situations. In an attempt to augment immune reconstitution and to improve clinical outcomes for patients with pediatric solid tumors, we are currently conducting trials of tumor vaccines administered with autologous lymphocyte infusions. Because clinical translation of our focuses on pediatric sarcomas, we are exploring the immunobiology of pediatric sarcomas. These studies have identified an important role for 4-1BB in immune responses to Ewing's sarcoma and have identified Ewing's sarcoma as exquisitely susceptible to TRAIL mediated cell death. In summary, we use the human model of a chemoresponsive pediatric solid tumor to investigate the biology of lymphopenia in mice and humans and are currently developing clinical trials aimed at exploiting alterations in T cell homeostasis induced by lymphopenia to improve the effectiveness of immunotherapy for cancer.
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