Abstract PO-098: Development of radioimmunotherapy using IL7 and FLT3 in a murine HPV related head and neck squamous cell carcinoma model
Authors: Yu Justin , Ross Richard B. , Darragh Laurel , Gadwa Jacob , Abdelazeem Khalid , Corbo Sophia , Hoen Maureen , Knitz Michael , Neupert Brooke , Nguyen Diemmy , Olimpo Nicholas , Van Court Benjamin , Karam Sana D. 
Published: September 2023

Background: Head and neck squamous cell carcinoma (HNSCC) is the most frequent cancer of the head and neck region, and an increasing proportion of this cancer has been linked to the human papilloma virus (HPV). Immunotherapy has emerged as an important modality in cancer treatment though remains underutilized in the treatment of HPV+ HNSCC. Recent literature suggests that B-cells play an important role in the immune response against HPV+ HNSCC through specific antibody targeting, tumor infiltration and formation of tertiary lymphoid structures. The receptors IL7 and FLT3 have been linked to promotion of B-cell formation and function and as a result serve as a valuable targets for immunomodulation. Methods: An orthotopic implantation model using the mEER cell line was utilized to establish a murine model to study HPV+ HNSCC. 100,000 mEER cells, which have been engineered to produce E6, E7, and HRAS, were implanted into the buccal mucosa. Mice were divided into 5 groups: untreated, radiotherapy (RT) only, RT+IL7, RT+FLT3, and RT+IL7+FLT3. IL7 was administered via intraperitoneal injection, and FLT3 ligand was given via hydrodynamic tail vein injection. Tumor growth was measured using electronic calipers, and overall survival was tracked. Mouse cheek bleeds were performed at time of tumor growth curve separation. Results: After 14 days post implantation, there was noted to be a statistically significant difference in tumor volume between the RT+IL7 group compared to the RT only and untreated groups (p&lt;0.001). This translated to a high cure rate after 30 days. 5 of 8 mice in the RT+IL7 group were found to be cured, compared to 3 out of 8 in the RT only. There was no detectable difference in tumor growth or cure rate between the RT+FLT3 mice compared to RT alone. In addition, tumor volumes of the RT+IL7+FLT3 group tracked similarly to the RT+IL7 group with no additional benefit on tumor reduction. Flow cytometry on circulating immune cells from cheek bleeding demonstrated decreased IgM expression on B-cells in the RT+IL7 group, suggesting that antibody class switching may be occurring. Conclusions: The combination of RT and IL7 caused reduced tumor growth in a HPV+ HNSCC murine model. The administration of FLT3 ligand did not provide any additional benefit to slowing tumor growth. Our current work indicates that circulating B-cells may play a role in the anti-tumor effect though future studies are needed to characterize changes in the TME after radioimmunotherapy.

Citation Format: Justin Yu, Richard B. Ross, Laurel Darragh, Jacob Gadwa, Khalid Abdelazeem, Sophia Corbo, Maureen Hoen, Michael Knitz, Brooke Neupert, Diemmy Nguyen, Nicholas Olimpo, Benjamin Van Court, Sana D. Karam. Development of radioimmunotherapy using IL7 and FLT3 in a murine HPV related head and neck squamous cell carcinoma model [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-098.