Keywords: Cancer immunotherapy, bone marrow transplantation, T lymphocyte danger model, cryoablation, adoptive immunotherapy.
The laboratory is currently investigating methods of augmenting immune responses against cancer in the setting of allogeneic bone marrow transplantation, or alloBMT. In alloBMT, the host’s immune system is destroyed by radiation therapy and is replaced by an immune system from a healthy donor. Alloreactive donor T cells recognize host cancer cells as “foreign” and destroy them, but also cause graft-versus-host disease (GVHD), a pathological attack on normal host tissues. We have developed non-toxic methods of inducing donor T cell engraftment without having to destroy the host immune system, and have recently found that tumor “vaccines”, crafted from the host’s tumor cells, can induce potent anti-tumor immunity after alloBMT without causing GVHD. We are currently employing tumors expressing defined antigens and tumor-specific transgenic T cells, which can be tracked in animals undergoing alloBMT. This model will be used to investigate the relative contributions of host versus donor, CD4+ versus CD8+, and alloreactive versus tumor-specific T cells in the eradication of malignancy following alloBMT.
Publications and Interests: https://jhu.pure.elsevier.com/en/persons/ephraim-j-fuchs