Chaperone Rich Cell Lysate (CRCL) Vaccine for Chronic Myelogenous Leukemia

摘要

We evaluated whether immunization of mice with dendritic cells (DCs) loaded with 12B1 murine bcr-abl+ leukemia -derived chaperone-rich cell lysates (CRCL) induced BCR-ABL specific immune responses in vivo. We found that splenocytes from mice immunized with DCs loaded with CRCL secreted interferon gamma (lFN-gamma) when re-stimulated with a BCR-ABL peptide, GFKQSSKAL, indicating that BCR-ABL peptides are chaperoned by 12B1 tumor derived CRCL. Splenocytes from mice primed with 12B1 CRCL secreted higher amounts of lFN-gamma and had higher cytolytic activity upon re-stimulation with 12B1 derived CRCL when compared to re stimulation with BCR-ABL peptide alone suggesting that other antigenic peptides may also be present in the antigen repertoire of 12B1 CRCL and contribute to its superior immunogenicity. We also investigated the effects of combining imatinib with CRCL immunotherapy against 12B1. We demonstrated that the combination of imatinib with DC loaded with 12B1-derived CRCL yielded high activation of anti-12B1 specific T cells, and potent anti-tumor activity resulting in tumor-free survival in up to 63% of mice with bcr-abl+ 12B1 tumors. Our data suggest that immunotherapy can be effectively combined with imatinib for the treatment of CML.