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.

Luznik, L., and Fuchs, E.J. (2002) Donor lymphocyte infusions to treat hematologic malignancies in relapse after allogeneic blood or marrow transplantation. Cancer Control 20:535-546 [PubMed]

Luznik, L., Engstrom, L.W., Iannone, R., and Fuchs, E.J. (2002) Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation. Biology of Blood and Marrow Transplantation 192:175-84 [PubMed]

O’Donnell, P.V., Luznik, L, Jones, R.J., Vogelsang, G.B., Leffell, M.S., Phelps, M., Rhubart, P., Cowan, K., Piantadosi, S., and Fuchs, E.J. (2002) Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biology of Blood and Marrow Transplantation 188:1633-1640 [PubMed]

Iannone, R., Luznik, L., Engstrom, L., Hawkins, A., Griffin , C., Noffsinger, L., Askin, F.B.,, Casella, J.F., and Fuchs, E.J. (2001) Effects of mixed hematopoietic chimerism in a mouse model of bone marrow transplantation for sickle cell anemia. Blood 171, 2421-2426 [PubMed]

Luznik, L., Iannone, R., Jalla, S., and Fuchs, E.J. (2001) Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide. Blood 193:1113-1121 [PubMed]