Tumor-Derived Chaperone-Rich Cell Lysate (CRCL) Can Be Effectively Combined with Syngeneic Bone Marrow Transplantation to Treat Bcr-abl⁺ Leukemia in a Murine Model.

We have previously reported that purified tumor derived chaperone-rich cell lysate (CRCL) containing multiple heat shock proteins (HSPs) is a promising cancer vaccine, capable of generating tumor-specific T cell responses and protective immunity in different animal tumor models. In this study, we have explored the therapeutic applicability of CRCL in the context of syngeneic bone marrow transplantation (BMT) to treat preexisting leukemia. BALB/c mice received a 10-fold LD₁₀₀ dose of bcr-abl⁺ leukemia cells (12B1) subcutaneously (s.c.) on day -7. On day -1, 900cGy of total body irradiation (TBI) was given followed by syngeneic bone marrow transplantation (BMT) on day 0. Transplanted mice received 20X10⁶ bone marrow cells along with 50X10⁶ splenocytes (SPC) intravenously (i.v.). We have demonstrated that BMT/SPC prolonged survival of mice by a median time of 7 days (median survival time [MST] from tumor inoculation of no BMT versus BMT/SPC =19 vs 26 days), however, all mice eventually died of disseminated leukemia. When recipients received BMT and SPC from syngeneic donors that had been previously immunized with 12B1-derived CRCL (immune BMT/SPC) the MST was increased to 29 days with 26.1% of transplanted mice surviving without tumor (p<0.01 immune BMT/SPC vs naive BMT/SPC). Vaccination of immune BMT/SPC recipients with 20 mg 12B1-derived CRCL in the early post-transplant period (day +1 and day +6) increased MST to 32 days (p<0.01 vs naïve BMT/SPC control) but did not significantly improve overall survival (26.3%) when compared to immune BMT/SPC mice not receiving post transplant 12B1-CRCL vaccine. Eleven to 17 weeks later, mice with no evidence of disease were re-challenged with 12B1 cells in one groin and A20 B cell leukemia cells in the opposite groin. Eighty percent of the mice demonstrated long term tumor specific immunity by rejecting the 12B1 rechallenge while 100% of the mice developed A20 tumors. Our results indicate that CRCL is a promising vaccine that can be used to generate specific anti-tumor immunity that can be effectively transferred to a host via BMT.