Abstract 6512: Tissue engineered metastases to improve cancer immunotherapy

Abstract

Abstract Background: Radiotherapy can induce the abscopal effect when combined with immune checkpoint inhibition. The main limitations to this treatment are the lack of control over the tumor microenvironment and the tumor is not amendable for radiosurgery. To overcome this, we hypothesize that using ex-vivo engineered cancer metastases treated with radiotherapy can improve the impact of the abscopal effect, as the immune cascade reaction is radiotherapy dose dependent and tumors can be exposed to higher amounts of radiation ex-vivo without the risk of radiation toxicity using our tissue engineered metastases model to boost immune response. Methods: Using B16F10 as a model, we first engineered B16F10 lung metastasis ex-vivo using decellularized rat lung biomatrix scaffolds. The engineered lung metastases were then lethally irradiated with 100 Gy of radiotherapy. The cells were then injected subcutaneously into tumor bearing C57BL6 mice in combination with anti PD-1 checkpoint inhibitor. Experimental groups included: no treatment, anti PD-1 only, cell lysate with and without anti PD-1, and irradiated engineered metastases with and without anti PD-1. All the mice were inoculated with 50,000 plastic grown B16F10 cells. On days 3, 6, and 9 the mice received immunotherapy and radiotherapy combinations based on their respective groups. The tumors were then analyzed by flow cytometry and IHC staining for different T cell populations. Results: We successfully engineered B16F10 lung metastasis ex vivo. We then demonstrated that mice treated irradiated engineered lung metastasis had significantly better survival than any other treatment arms with median survival twice that of irradiated cells (P <0.01). Correlative studies showed that mice that received irradiated engineered metastasis had increased CD8+ cells and lower Treg cells when compared to other experimental groups. This indicates that engineered metastasis increased immune activation and response to tumor. Conclusions: Our data demonstrates that engineered metastases can indeed improve cancer immunotherapy and induce a robust abscopal/vaccine effect. Citation Format: Nikhila Reddy Sultanpuram. Tissue engineered metastases to improve cancer immunotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6512.