In MCA-induced sarcoma models, booster vaccination with GM-CSF-secreting whole-cell tumor vaccines maintain or improve efficacy but may alter trafficking of tumor-specific T cells (VAC13P.1128)

Abstract

Abstract Previously, we reported that while a single vaccination effectively generated therapeutic tumor-specific T cells for adoptive immunotherapy (AIT), repeated vaccination with the poorly immunogenic B16BL6 melanoma, modified to secrete GM-CSF, induced high levels of CD4+FoxP3+ T regulatory (Treg) cells and AIT with spleen cells was non-therapeutic. The effect could be overcome by transient depletion of CD4+ T cells, confirming the effect of Treg cells. Here experiments were performed to test whether this suppressive effect was observed in active-specific protection in 2 sarcoma models, MCA-304 and MCA-310. Mice were vaccinated once or thrice with either irradiated parental sarcoma or that sarcoma expressing GM-CSF. We did not observe significant changes in percentage or total count of splenic Treg cells under any conditions, however, tumor-specific IFN-γ release decreased in mice thrice vaccinated with GM-CSF-secreting tumors compared to parental (p < 0.001). Importantly, multiple vaccination offered tumor protection that was as good or better than single vaccination. In the most strongly immunogenic tumor, MCA-304, both single and triple vaccination with parental or GM-CSF-secreting tumors provided 100% protection. However, in the weakly immunogenic, MCA-310 sarcoma, multiple vaccinations improved effectiveness with the greatest effect seen with the GM-CSF-secreting MCA-310. Our results provide a rationale for the continued use of GM-CSF as a cancer vaccine adjuvant.