Abstract 697: Enhanced tumor control and survival in solid tumor models following combined low dose radiotherapy and T cell therapy

Abstract Background: Solid tumors remain a significant challenge in cancer therapy due to their resistance to conventional treatments. Chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising approach for treating solid tumors, but its effectiveness is often limited by the poor infiltration of CAR-T cells into the tumor microenvironment. Thus, enhancing a robust infiltration of chimeric antigen receptor T cells into solid tumors is essential for an effective antitumor response and therapeutic success. Methods: In this study, we investigated the combined effects of multiple doses of low-dose radiotherapy (LD-RT) and CAR T-cell therapy on tumor growth and survival using two models of NSG mice implanted with gastric carcinoma (GSU) or pancreatic adenocarcinoma (CAPAN-2) cells. The engineered CAR-T cells were designed to target guanyl cyclase-C (GCC) or mesothelin, respectively. Furthermore, our study employed atomic force microscopy (AFM) in a small cohort to investigate the impact of LD-RT and CAR-T cell therapy on tumor stiffness and plasticity. Results: The synergistic effect of combining low-dose radiotherapy (LD-RT) with T-cell therapy resulted in enhanced tumor control and prolonged survival in mice with tumors, surpassing the outcomes observed with either monotherapy alone. This combined treatment holds promise for improving responses in patients with solid tumors by leveraging LD-RT to enhance the intratumoral infiltration of effector T cells. Our findings suggest that the nanomechanical signature may be a potential biomarker for LD-RT combined CAR T cell therapy in solid tumors. Conclusions: Our findings substantially contribute to treating solid tumors using cell therapies, highlighting the potential for improved infiltration of adoptively transferred T cells following radiotherapy (RT), which can transform existing therapeutic strategies for solid tumors while minimizing toxicity. Citation Format: Nahum Puebla, Gitika Srivastava, Sara Nizzero, Natalie Wall Fowlkes, Hampartsoum Barsoumian, Yun Hu, Carola Leuschner, Thomas Riad, Marko Loparic, Marija Plodinec, James Welsh. Enhanced tumor control and survival in solid tumor models following combined low dose radiotherapy and T cell therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 697.