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Article

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

1
Department of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada
2
Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4K1, Canada
*
Authors to whom correspondence should be addressed.
The authors contributed equally to this publication.
Academic Editor: Peter C. Hart
Int. J. Mol. Sci. 2021, 22(9), 4843; https://doi.org/10.3390/ijms22094843
Received: 8 April 2021 / Revised: 28 April 2021 / Accepted: 1 May 2021 / Published: 3 May 2021
(This article belongs to the Special Issue Pharmacologic Targeting of the Tumor Microenvironment)
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 radiolabeled 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. View Full-Text
Keywords: triple negative breast cancer; immunotherapy; immune checkpoint therapy; radionuclide therapy triple negative breast cancer; immunotherapy; immune checkpoint therapy; radionuclide therapy
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MDPI and ACS Style

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. https://doi.org/10.3390/ijms22094843

AMA Style

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. International Journal of Molecular Sciences. 2021; 22(9):4843. https://doi.org/10.3390/ijms22094843

Chicago/Turabian Style

Vito, Alyssa, Stephanie Rathmann, Natalie Mercanti, Nader El-Sayes, Karen Mossman, and John Valliant. 2021. "Combined Radionuclide Therapy and Immunotherapy for Treatment of Triple Negative Breast Cancer" International Journal of Molecular Sciences 22, no. 9: 4843. https://doi.org/10.3390/ijms22094843

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