Abstract P013: Low-dose radiation acts as a promising preconditioning regimen for dendritic cell vaccines
Authors: Kwon Eric , Namen Shelby , Kang Solomon , Wiloughby Colin , Zhang Kevin , Pandey Gaurav , DeSelm Carl J. 
Published: January 2025

Background: 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 whole-body and tumor-directed low-dose radiation (LD RT), cyclophosphamide, and paclitaxel as preconditioning regiments for antigen-loaded dendritic cell vaccine-induced antitumor T-cell response. Methods: Syngeneic KP tumors were engineered with ovalbumin and injected subcutaneously into the flank of wild-type B6 mice. Preconditioning regiments of LD RT (2 Gy to the whole body), cyclophosphamide (250mg/kg), LD RT (2 Gy to the whole body) + cyclophosphamide (250mg/kg), paclitaxel (20mg/kg), or nothing (control) were given on day 4. Bone marrow dendritic cells (DCs) were electroporated with ovalbumin protein, and then one million cells were injected i.v. on days 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: The usage of cyclophosphamide and paclitaxel resulted in a higher tumor burden than the no preconditioning group, which indicated that lymphodepletion chemotherapy should be avoided during dendritic cell vaccines, unlike in other cellular therapies such as CAR T-cells. Whole-body LD RT performed significantly better than the control group in both tumor burden and survival, which led to further examination of LD RT and the potential difference in whole-body and tumor-specific LD RT as a preconditioning regimen. There was a significant difference in the percentage of SIINFEKL tetramer+ T-cells amongst all CD8+ cells when LD RT was administered compared to other preconditioning regimens. Furthermore, whole-body LD RT produced a significantly higher percentage of SIINFEKL tetramer+ T-cells than tumor-directed LD RT. The overall survival rate and tumor burden of subjects receiving whole-body or tumor LD RT significantly improved compared to all other groups. Interestingly, intergroup comparisons of tumor growth and survival rates between the whole-body and tumor LD-RT groups had no significant difference. Conclusions: Here, we find that LD-RT is the most effective preconditioning regimen before dendritic cell vaccination for inducing an antitumor T-cell response and achieving tumor control over time. LD RT provides a promising method to supplement dendritic cell vaccination to potentially improve patient outcomes. However, further study of the differences in whole-body and tumor-specific LD RT is necessary to determine the most ideal preconditioning regimen for dendritic cell vaccination.

Citation Format: Eric Kwon, Shelby Namen, Solomon Kang, Colin Wiloughby, Kevin Zhang, Gaurav Pandey, Carl J. DeSelm.Low-dose radiation acts as a promising preconditioning regimen for dendritic cell vaccines.[abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr P013