Treatment with GM-CSF Secreting Myeloid Leukemia Cell Vaccine Prior to Autologous-BMT Improves the Survival of Leukemia-Challenged Mice

Abstract

Vaccination with irradiated autologous tumor cells, engineered to secrete granulocyte macrophage-colony stimulating factor (GM-CSF) (GM tumor), can generate potent antitumor effects when combined with autologous bone marrow transplantation (BMT). That notwithstanding, the post-BMT milieu, characterized by marked cytopenia, can pose a challenge to the implementation of vaccine immunotherapies. To bypass this problem, partial post-BMT immune reconstitution has been allowed to develop prior to vaccination. However, delaying vaccination can also potentially allow the expansion of residual tumor cells. Other approaches have used reinfusion of "primed" autologous lymphocytes and multiple administrations of GM tumor cells, which required the processing of large amounts of tumor. Utilizing the MMB3.19 murine myeloid leukemia model, we tested whether a single dose of GM tumor cells, 7 days prior to syngeneic BMT, could be a curative treatment in MMB3.19-challenged recipient mice. This vaccination protocol significantly improved survival of mice by eliciting long-lasting host immune responses that survived lethal irradiation, and were even protective against post-BMT tumor rechallenge. Furthermore, we demonstrated that mature donor lymphocytes can also play a limited role in mounting the antitumor response, but our pre-BMT vaccination strategy obviated the need for either established de novo immune reconstitution or the use of multiple post-BMT immunizations.