Abstract 232: The abscopal effect: modelling and predicting the effect of radiation therapy on non-irradiated tumour when combined with immune checkpoint blockers

Abstract We have developed preclinical and clinical ‘Virtual Tumour' (‘VT') models that can predict how a tumour will respond to drug exposure. This agent-based method is particularly suitable for modelling not only tumour cells, but also those involved in the immune response, and interactions between cells (1-3). The purpose of the study was to extend the VT platform to be able to model simultaneously i) the response of a tumour treated with radiation only or in combination with immune-checkpoint blockers, ii) the tumour response in areas where radiation has not been performed in the absence/presence of an immune-checkpoint blocker. Building on previous work, in which the VT platform was extended by the addition of a module that captures the synergistic of PD(L)-1 blockade with conventional anticancer therapies, we have further expanded the model to integrate the immune-checkpoint blocker module with other immune species activated by irradiation of the target tumour - in particular circulating CD8+ T cells - in order to be able to mimic the systemic abscopal effect. Ultimately, this expansion enables us to simulate the effect of tumour growth control on out-of-field tumour lesions when delivered in combination with an immune-checkpoint blocker. Through preclinical case studies derived from the literature (4) we demonstrate that the extended VT can be applied to simulate the efficacy of diverse radiation regimens in combination with immune-checkpoint blockers, and correctly describe the combination treatment effect on the progression of irradiated and non-irradiated tumours. Furthermore, we demonstrate that the model can be applied to optimize the timing of the combination in order to maximize the systemic efficacy of the treatment. Our enhanced VT capability represents a key step towards a strategic tool for optimizing dosing and scheduling of immune-checkpoint block and radiation combinations. [1] Brightman, FA et al., Abstract 680. Cancer Res 75, 4866-66 (2015). [2] Ortega, F et al., Abstract 4866. Cancer Res 79, (13 Suppl) (2019). [3] Orrell, DA et al., Abstract 4918. Cancer Res 71, (8 Suppl) (2011). [4] Dovedi, S et al., Clin Cancer Res 23(18); 5514-26 (2017). Citation Format: Frances Brightman, Fernando Ortega, David Orrell, Christophe Chassagnole. The abscopal effect: modelling and predicting the effect of radiation therapy on non-irradiated tumour when combined with immune checkpoint blockers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 232.