Induction of cell death in malignant cells and regulatory T cells in the tumor microenvironment by targeting CD137
Regulatory T cells (Tregs) contribute significantly to the immunosuppressive nature of the tumor microenvironment which is a main barrier for immunotherapies of solid cancers. Reducing Treg numbers enhances anti-tumor immune responses but current depletion strategies also impair effector T cells (Te...
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| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2443265 |
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| author | Rui Sun Kang Yi Lee Yu Mei Emily Nickles Jia Le Lin Runze Xia Haiyan Liu Herbert Schwarz |
| author_facet | Rui Sun Kang Yi Lee Yu Mei Emily Nickles Jia Le Lin Runze Xia Haiyan Liu Herbert Schwarz |
| author_sort | Rui Sun |
| collection | DOAJ |
| description | Regulatory T cells (Tregs) contribute significantly to the immunosuppressive nature of the tumor microenvironment which is a main barrier for immunotherapies of solid cancers. Reducing Treg numbers enhances anti-tumor immune responses but current depletion strategies also impair effector T cells (Teffs), potentially leading to reduced anti-tumor immunity and/or autoimmune diseases. CD137 has been identified as the most differentially expressed gene between peripheral Tregs and intratumoral Tregs in virtually all solid cancers. Further, CD137 is expressed by malignant cells of certain cancers, making it a potential target for tumor immunotherapy. Here, we report the development of a fully human anti-human CD137 antibody of the IgG1 isotype, clone P1A1, that induces antibody-dependent cell-mediated cytotoxicity (ADCC) in CD137+ Tregs and cancer cells. P1A1 cross-reacts with murine CD137 which allowed testing murine chimeric P1A1 in syngeneic murine tumor models where P1A1 significantly reduced the number of CD137+ Tregs and inhibited tumor growth in a murine hepatocellular carcinoma (HCC) and a melanoma lung metastasis model. P1A1 can also be internalized thus enabling it as a carrier for drugs to target CD137+ Tregs and cancer cells. These anti-cancer properties suggest a translation of P1A1 to human immunotherapy. |
| format | Article |
| id | doaj-art-b40f6d04524b4e919ec2e72290dbff40 |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-b40f6d04524b4e919ec2e72290dbff402025-08-20T02:32:29ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2024.2443265Induction of cell death in malignant cells and regulatory T cells in the tumor microenvironment by targeting CD137Rui Sun0Kang Yi Lee1Yu Mei2Emily Nickles3Jia Le Lin4Runze Xia5Haiyan Liu6Herbert Schwarz7Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeNUS Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, SingaporeNUS Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, SingaporeDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeNUS Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, SingaporeDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeRegulatory T cells (Tregs) contribute significantly to the immunosuppressive nature of the tumor microenvironment which is a main barrier for immunotherapies of solid cancers. Reducing Treg numbers enhances anti-tumor immune responses but current depletion strategies also impair effector T cells (Teffs), potentially leading to reduced anti-tumor immunity and/or autoimmune diseases. CD137 has been identified as the most differentially expressed gene between peripheral Tregs and intratumoral Tregs in virtually all solid cancers. Further, CD137 is expressed by malignant cells of certain cancers, making it a potential target for tumor immunotherapy. Here, we report the development of a fully human anti-human CD137 antibody of the IgG1 isotype, clone P1A1, that induces antibody-dependent cell-mediated cytotoxicity (ADCC) in CD137+ Tregs and cancer cells. P1A1 cross-reacts with murine CD137 which allowed testing murine chimeric P1A1 in syngeneic murine tumor models where P1A1 significantly reduced the number of CD137+ Tregs and inhibited tumor growth in a murine hepatocellular carcinoma (HCC) and a melanoma lung metastasis model. P1A1 can also be internalized thus enabling it as a carrier for drugs to target CD137+ Tregs and cancer cells. These anti-cancer properties suggest a translation of P1A1 to human immunotherapy.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2443265AntibodyCD137depletionregulatory T celltumor microenvironment |
| spellingShingle | Rui Sun Kang Yi Lee Yu Mei Emily Nickles Jia Le Lin Runze Xia Haiyan Liu Herbert Schwarz Induction of cell death in malignant cells and regulatory T cells in the tumor microenvironment by targeting CD137 OncoImmunology Antibody CD137 depletion regulatory T cell tumor microenvironment |
| title | Induction of cell death in malignant cells and regulatory T cells in the tumor microenvironment by targeting CD137 |
| title_full | Induction of cell death in malignant cells and regulatory T cells in the tumor microenvironment by targeting CD137 |
| title_fullStr | Induction of cell death in malignant cells and regulatory T cells in the tumor microenvironment by targeting CD137 |
| title_full_unstemmed | Induction of cell death in malignant cells and regulatory T cells in the tumor microenvironment by targeting CD137 |
| title_short | Induction of cell death in malignant cells and regulatory T cells in the tumor microenvironment by targeting CD137 |
| title_sort | induction of cell death in malignant cells and regulatory t cells in the tumor microenvironment by targeting cd137 |
| topic | Antibody CD137 depletion regulatory T cell tumor microenvironment |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2443265 |
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