Preconditioning with Low-Dose Radiation Improves Antitumor Immunity and Survival in DC-Vaccinated Mice

Preconditioning regimens are essential for the immunologic success of cell therapies like CAR T cells. Nevertheless, their effect on cancer vaccines is underexplored, and preconditioning regimens are generally absent from cancer vaccine clinical trials. To address this knowledge gap, we evaluated the impact of various preconditioning strategies on dendritic cell (DC) vaccine efficacy in a murine tumor model. Mice bearing syngeneic tumors received preconditioning with 2 Gy low-dose radiation therapy (LD RT; whole-body or tumor-only), cyclophosphamide, paclitaxel, LD RT plus cyclophosphamide, or no preconditioning, followed by administration of antigen-loaded DCs. Whether whole-body or tumor-directed, LD RT preconditioning significantly enhanced vaccine-induced antitumor CD8⁺ T cell responses and improved survival compared to DC vaccine alone and all other preconditioning groups. Cyclophosphamide preconditioning reduced vaccine efficacy and negated the benefits of LD RT, while paclitaxel had no significant effect. Notably, whole-body LD RT induced the strongest tumor antigen-specific T cell response. These findings suggest that preconditioning regimens can significantly influence cancer vaccine outcomes, as in CAR T cell therapy. Rational selection of preconditioning agents may either maximize or minimize the therapeutic potential of DC cancer vaccines and should be considered carefully in clinical trials.