Working Paper Article Version 1 This version is not peer-reviewed

Combined Radionuclide Therapy and Immunotherapy for Treatment of Triple Negative Breast Cancer

Version 1 : Received: 8 April 2021 / Approved: 9 April 2021 / Online: 9 April 2021 (13:26:23 CEST)

A peer-reviewed article of this Preprint also exists.

Vito, A.; Rathmann, S.; Mercanti, N.; El-Sayes, N.; Mossman, K.; Valliant, J. Combined Radionuclide Therapy and Immunotherapy for Treatment of Triple Negative Breast Cancer. Int. J. Mol. Sci. 2021, 22, 4843. Vito, A.; Rathmann, S.; Mercanti, N.; El-Sayes, N.; Mossman, K.; Valliant, J. Combined Radionuclide Therapy and Immunotherapy for Treatment of Triple Negative Breast Cancer. Int. J. Mol. Sci. 2021, 22, 4843.

Journal reference: Int. J. Mol. Sci. 2021, 22, 4843
DOI: 10.3390/ijms22094843

Abstract

Triple negative breast cancer (TNBC) is an aggressive subtype of the disease with poor clinical outcomes and limited therapeutic options. Immune checkpoint blockade (CP) has surged to the forefront of cancer therapies with widespread clinical success in a variety of cancer types. However, the percentage of TNBC patients that benefit from CP as a monotherapy is low and clinical trials have shown the need for combined therapeutic modalities. Specifically, there has been interest in combining CP therapy with radiation therapy where clinical studies primarily with external beam have suggested their therapeutic synergy, contributing to the development of anti-tumor immunity. Here, we have developed a therapeutic platform combining radionuclide therapy (RT) and immunotherapy utilizing a radiolabelled biomolecule and CP in an E0771 murine TNBC tumor model. Survival studies show that while neither monotherapy is able to improve therapeutic outcomes, the combination of RT + CP extended overall survival. Histologic analysis showed that RT + CP increased necrotic tissue within the tumor and decreased levels of F4/80+ macrophages. Flow cytometry analysis of the peripheral blood also showed that RT + CP suppressed macrophages and myeloid-derived suppressive cells, both of which actively contribute to immune escape and tumor relapse.

Keywords

triple negative breast cancer; immunotherapy; immune checkpoint therapy; radionuclide therapy

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