Semiallogeneic cell hybrids as therapeutic vaccines for cancer

The authors have engineered a cell line that can be used in human studies a s a universal donor cell for the formation of semiallogeneic cell hybrids a fter fusion with patient-derived tumor cells. These hybrids can be irradiat ed and injected as a patient-tailored therapeutic vaccine in patients affec ted by virtually any type of cancer. A crucial step in this research effort has been the derivation of an allogeneic cell line (FO1-12) that expresses both a dominant selectable marker (neomycin resistance) and a recessive se lectable marker (sensitivity to hypoxanthine, aminopterin, and thymidine), which allows easy selection of semiallogeneic cell hybrids derived from the fusion of FO1-12 cells with patient-derived turner cells. Tumor-infiltrati ng lymphocytes derived from select patients with melanoma and exposed to se miallogeneic cell hybrids from the same patient were better able to specifi cally lyse autologous turner cells. Furthermore, FO1-12 cells express carci noembryonic antigen, which is ubiquitous in adenocarcinomas. and fusion of FO1-12 cells with various patient-derived adenocarcinoma cells showed that the hybrid cells also express carcinoembryonic antigen. Because of the resu lts of these preclinical studies, the authors were given permission to use semiallogeneic cell hybrids for immunotherapy of patients with metastatic m elanoma or metastatic adenocarcinoma who had not responded to standard trea tment regimens. Treatment with semiallogeneic vaccines is associated with m inimal or no toxicity and can induce a specific anti-tumor immune response.