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ResearchIn-Press PreviewImmunologyOncology Open Access | 10.1172/jci.insight.198701

PD-1-targeted IL-15 mutein activates CD8+ and CD4+ T cells in infection and cancer

Isaraphorn Pratumchai,1 Marie Bernardo,2 Julien Tessier,2 Jaroslav Zak,1 Kristi L. Marquardt,1 Joon Sang Lee,2 Maheeka Bimal,1 AHyun Choi,2 Anthony M. Byers,3 Mikielia G. Devonish,3 Roberto Carrio,3 Dan Lu,4 Stella A. Martomo,4 Jeegar Patel,4 Yu-an Zhang,2 Ingeborg M. Langohr,2 Virna Cortez-Retamozo,2 Dinesh S. Bangari,2 Angela Hadjipanayis,2 Xiangming Li,2 Valeria R. Fantin,2 Donald R. Shaffer,2 and John R. Teijaro5

1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

Find articles by Pratumchai, I. in: PubMed | Google Scholar

1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, United States of America

2Sanofi, Cambridge, United States of America

3Sanofi Vaccines, Orlando, United States of America

4Kadmon Corporation, A Sanofi Company, New York, United States of America

5Department of Immunology and Microbiology, The Scripps Resarch Institute, La Jolla, United States of America

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Published April 30, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.198701.
Copyright © 2026, Pratumchai et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 30, 2026 - Version history
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Abstract

Immune checkpoint inhibitors have transformed cancer therapy, yet many patients fail to achieve durable responses due to insufficient T cell reinvigoration. Cytokines offer promise for enhancing immunotherapy, but their clinical use is limited by toxicity and a narrow therapeutic index. Immunocytokines, engineered fusion proteins combining antibody specificity with cytokine activity, aim to overcome these challenges by targeting cytokine delivery to immune cells or the tumor microenvironment. We describe SAR445877 (SAR’877), a novel PD-1-targeted immunocytokine that fuses a high-affinity anti-PD-1 antibody with a detuned IL-15/IL-15Rα sushi domain complex. SAR’877 blocks PD-1/PD-L1 and PD-1/PD-L2 interactions while selectively delivering IL-15 signals to PD-1+ T cells, enhancing proliferation and activation of antigen-experienced CD8+ and CD4+ T cells and NK cells, while minimizing systemic inflammation. Mechanistically, SAR’877 activates STAT5 signaling in PD-1+ lymphocytes and restores effector function in exhausted T cells. In preclinical models, a murine surrogate of SAR’877 accelerated viral clearance and induced robust anti-tumor immunity by expanding cytotoxic CD8+ T cells and promoting Th1 polarization. Notably, SAR’877 outperformed anti-PD-1 plus untargeted IL-15, highlighting the therapeutic potential of targeted IL-15 delivery. These findings position SAR’877 as a promising next-generation immunotherapy with enhanced efficacy and reduced cytokine-associated toxicities.

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  • Version 1 (April 30, 2026): In-Press Preview
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