Low-dose radiation as a preconditioning regimen for dendritic cell vaccines.

Abstract

e14519 Background: Dendritic cells are potent antigen-presenting cells that induce the adaptive immune system to protect against cancer. While anti-tumor immunity can be improved with dendritic cell vaccines, it is not fully known what approved preconditioning agents, if any, improve dendritic cell vaccine-induced antitumor T-cell response and tumor elimination. We explored the effect of low-dose radiation (LDR), cyclophosphamide, and paclitaxel as preconditioning regiments for a dendritic cell vaccine. Methods: KP tumors were engineered with ovalbumin and orthotopically injected subcutaneously (SQ) into the flank of wild type B6 mice. Preconditioning regiments of a control, LDR (2 Gy), cyclophosphamide (20mg/kg), LDR (2 Gy) + cyclophosphamide (20mg/kg), and paclitaxel (20mg/kg) were given on day 4. Bone marrow dendritic cells (DCs) were electroporated with ovalbumin peptide SIINFEKL and then one million cells were injected i.v. on day 5 and 8. Blood collection was done and ovalbumin-specific T-cell populations were examined by tetramer staining for SIINFEKL-specific TCR over time. Tumor size was measured over time and survival data was analyzed accordingly. Results: LDR effectively produced a significant increase in CD8+ SIINFEKL tetramer+ T-cell count per uL of blood compared to the non-preconditioned group. In addition, this LDR preconditioning regiment produced a significantly improved tumor response over time. The overall survival rate of subjects receiving LDR was significantly improved compared to all other groups. Conclusions: Here, we find that LDR is most effective as a preconditioning regimen prior to dendritic cell vaccination for inducing an antitumor T-cell response and achieving tumor control over time. LDR provides a promising method to supplement dendritic cell vaccination and potentially improve patient outcomes. Further study is needed to confirm its efficacy.