Combination of CD80 and granulocyte-macrophage colony-stimulating factor coexpression by a leukemia cell vaccine: Preclinical studies in a murine model recapitulating Philadelphia chromosome-positive acute lymphoblastic leukemia

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a highly aggressive malignancy caused by the bcr-abl translocation oncogene . To explore alternative treatments for Ph+ ALL we tested gene-modified cel l vaccines in the BALB/c-derived BM185 leukemia model. We compared the effi cacy of BM185 cell vaccine expressing CD80 alone or in combination with IL- 2 or GM-CSF. Mice injected with viable BM185 leukemia cells modified to exp ress CD80 and GM-CSF (BM185/CD80+GM-CSF) showed the highest leukemia reject ion rates, Cell vaccines consisting of irradiated BM185/CD80+GM-CSF cells a dministered subcutaneously stimulated a potent cytotoxic T lymphocyte (CTL) response against parental BM185. Histological examination of the vaccinati on site showed a large concentration of immune cells, Administration of the BM185/CD80+GM-CSF cell vaccine before intravenous challenge with parental cells caused strong inhibition of leukemia development. Vaccination after s ubcutaneous challenge with BM185 cells caused efficient elimination of leuk emia promoting 40-60% long-term survival rates. The immunization efficacy o f the BM185/CD80+GM-CSF cell vaccine was directly correlated with the perce ntage of cells expressing the transgenes. In all, this preclinical study sh ows that leukemia cell vaccines coexpressing CD80 and GM-CSF can potentiall y be explored for immunotherapy in Ph+ ALL patients.