Combined treatment of squamous cell carcinoma in mice with paclitaxel and a unique DNA-based cellular vaccine enriched for immunotherapeutic cells: Enrichment of a squamous carcinoma vaccine

Abstract

We describe a new vaccination strategy for squamous cell carcinoma. In a mouse model, the vaccine is prepared by transfer of unfractionated DNA-fragments (25 kb) from KLN205 cells, a squamous carcinoma cell line (DBA/2 mouse origin [H-2(d)]) into LM cells, a highly immunogenic mouse fibroblast cell line that expresses allogeneic major histocompatibility complex (MHC) class I-determinants (H-2(k)). The number of vaccine cells can then be expanded for multiple immunizations, as desired. As only a small proportion of the transfected cell population was expected to have incorporated DNA segments that included genes specifying antigens associated with the squamous carcinoma cells, we devised a novel strategy to enrich the vaccine for cells that induced immunity to the squamous carcinoma cells. Twenty-five percent of tumor-bearing mice treated by immunization with the vaccine appeared to have rejected the squamous carcinoma cells; they survived indefinitely (more than 70 days). The therapeutic benefits of the enriched vaccine could be further enhanced by treating the tumor-bearing mice with paclitaxel, a chemotherapeutic agent, followed by immunization with the enriched vaccine. Under these circumstances, 75% of mice with squamous carcinoma appeared to have rejected the squamous carcinoma cells. Toxic effects including the development of autoimmune disease were not detected in tumor-bearing mice receiving the combined therapy.