PEGylated liposomal doxorubicin improves oral cancer response to radio-immunotherapy

Abstract Introduction: The immunosuppressive tumor microenvironment (TME) in oral cancer inhibits response to conventional treatment (surgery +/- chemoradiotherapy) and check-point inhibitor (αPD1) immunotherapy. The chemotherapeutic agent doxorubicin and its PEGylated liposomal nanoparticle formulation (PLD) have been shown to target myeloid derived suppressor cells (MDSCs) in the TME. In this preclinical work, we investigated whether PLD improves response to radio-immunotherapy in a highly aggressive and immunologically ‘cold’ oral cancer model. Experimental Procedure: Studies were performed in the MOC2 syngeneic mouse model of oral cancer. Mice were randomized to one of seven treatment groups: αPD1, Radiation (XRT), αPD1+XRT, PLD, PLD+αPD1, PLD+XRT, PLD+αPD1+XRT. High-resolution nanoparticle contrast-enhanced computed tomography (nCECT) imaging was performed, and whole-body T2-weighted magnetic resonance imaging (MRI) used to monitor primary tumor response and development of metastases. Response evaluation criteria in solid tumors (RECIST) were used to evaluate treatment outcomes. Results: Tumors in all non-PLD groups were treatment resistant and grew progressively, consistent with the immunologically ‘cold’ MOC2 model. In contrast, all PLD groups showed tumor regression with 25-38% complete responders (CR) and 12-88% partial responders (PR) while all animals in non-PLD groups showed progressive disease (PD). MR imaging identified a high incidence of regional and distant metastases in the non-PLD groups while the PLD groups showed decreased regional and no distant metastases (Table 1). Presence of metastases was confirmed by nCECT imaging and histopathological analysis. Conclusion: PLD improved response to radio-immunotherapy in a highly aggressive immunologically ‘cold’ mouse model of oral cancer while simultaneously preventing disease progression and metastasis. Citation Format: Laxman Devkota, Rohan Bhavane, Andrew Badachhape, Ratna Veeramachaneni, Renuka Menon, Prajwal Bhandari, Sofia Cortes, Fabio Henrique Brasil Da Costa, Ketan Ghaghada, Simon Young, Andrew G. Sikora, Ananth V. Annapragada. PEGylated liposomal doxorubicin improves oral cancer response to radio-immunotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5174.