Abstract 1303: FAP-targeted molecular radiotherapy attenuates tumor growth and synergizes with immunotherapy for the treatment of malignant melanoma

Abstract

Abstract Immunotherapy has drastically improved outcomes in many patients with melanoma, however the majority do not attain a durable response to treatment and therefore additional agents are desperately needed. Here, we tested the efficacy of 177Lu-FAPI-04, a novel FAP-targeted radiotherapy, alone and in combination with anti-PD-1 and anti-CTLA-4 immunotherapy in a mouse model of melanoma to attenuate tumor growth. Using B16F10 murine melanoma cells, we implanted tumors in C57BL/6 mice. Animals were divided into four groups: untreated control, molecular targeted 177Lu-FAPI-04 radiotherapy treatment, immunotherapy treatment, and combined radio- and immunotherapy treatment. We assessed tumor growth over time and animals were sacrificed at 21 days. After sacrifice, tumors were dissected out and preserved for immunohistochemistry and flow cytometry. Growth curves demonstrated that immunotherapy and radiotherapy each individually attenuated tumor growth, but together they resulted in tumor regression in the majority of animals. Immunohistochemistry demonstrated increased caspase-3 staining in tumors treated with combined 177Lu-FAPI-04 radiotherapy and immunotherapy compared to untreated tumors or tumors treated with either therapy alone indicating an increase in apoptotic cell death. Ki67 expression exhibited inverse staining with moderate expression in untreated samples, low expression in immunotherapy and radiotherapy treated samples, and no staining in tumors treated with combined therapy. Flow cytometric analysis demonstrated that tumors treated with either therapy exhibited an increase in M2 macrophages, however this population was obliterated in dual-treated tumors. Together, these data support that targeting FAP with targeted radiotherapy is an effective treatment which synergizes with immunotherapy to modulate cells of the myeloid lineage as an effective anticancer therapy for melanoma. Future translational studies are needed to further study the synergies between FAP-targeted radiotherapies and immunotherapy. Citation Format: Kathleen M. Capaccione, Mikhail Doubrovin, Brian Braumuller, Dvora Leibowiz, Nikunj Bhatt, Andrei Molotkov, Michael Kissner, Fatemeh Momen-Heravi, Akiva Mintz. FAP-targeted molecular radiotherapy attenuates tumor growth and synergizes with immunotherapy for the treatment of malignant melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1303.