2874 - Nanoparticles Reassembled Whole Cancer Cell Components, Detecting Tumor-Specific T Cells, and the Abscopal Effect

Z. Gao¹, Q. Zhao¹, J. Xue¹, Y. Yao¹, M. Liu², and S. Qin¹; ¹1st Affiliated Hospital of Soochow University, Suzhou, China, ²Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University,, Suzhou, China

Purpose/Objective(s): The mechanism underlying the abscopal effect induced by radiotherapy (RT) remains unclear. Tumor-specific T cells generated plays a crucial role during this procedure. However, it’s still challenging to monitor those T cells. Based on this situation, we innovatively established one technology which uses nanoparticles reassembled whole cancer cell components to detect tumor-specific T cells. Through the utilization of this detection approach, we can precisely elucidate the impact of different radiotherapy doses and fraction on immune system activation, thereby aiding in our exploration of the underlying mechanisms behind the abscopal effect. Materials/

Methods: Tumor lysis from mice were used to make nanoparticles. C57 mice were inoculated subcutaneous(s.c.) with the syngeneic EO771 breast cancer cells or LLC lung cancer cells, considering the left and right sides as the primary and abscopal sides, respectively. RT was delivered exclusively to the primary tumor in 9Gy × 3 fractions. Subcutaneous injection of nanoparticles to the primary tumor was performed on days 3, 6, 9, 14, and 19 post-tumor inoculation. Tumor size was measured every three days. Fourteen days after RT, tumor-specific T cell detection technology was employed to assess the proportion of tumor-specific T cells in draining lymph nodes, spleen, and peripheral blood.
Results: In the breast cancer tumor model, we observed that both RT and nanoparticle therapy, as well as their combination, exhibited significant tumor suppression effects on the primary side. Furthermore, the combination therapy group on the abscopal side showed a significant difference compared to the single nanoparticle therapy group (average tumor volumes of 235.2 mm³ vs 88.5 mm³, P=0.0194), indicating a clear abscopal effect. In the LLC tumor model, tumor-specific T cell detection technology (IFN-g⁺CD8⁺T/CD8⁺T=3.43%) in draining lymph nodes detected significantly higher levels of tumor-specific T cells compared to conventional detection methods (IFN-g⁺CD8⁺T/CD8⁺T=0.39%), indicating its heightened sensitivity. Moreover, under the use of this detection technology, the proportion of tumor-specific T cells in the combined therapy group (IFN-g⁺CD8⁺T/CD8⁺T=3.43%) was significantly higher than that in the control group (IFN-g⁺CD8⁺T/CD8⁺T=0.18%), consistent with the abscopal effect observed in the EO771 model. This indicates that the detection technology can represent the occurrence of abscopal effect with its accuracy.
Conclusion: The combined use of nanoparticles loaded with tumor components and radiation therapy can induce a significant abscopal effect. Additionally, utilizing tumor-specific T cell detection technology based on this approach enables the detection of tumor-specific T cells in LLC tumor models treated similarly. This phenomenon demonstrates the advantage of this detection method and suggests its potential for inducing abscopal effects, thereby aiding in the understanding of its underlying mechanisms.