Empowerment of CAR-T cells by IL-7 and IL-15 boosts their efficacy against HER2-positive tumors with enhanced expansion and persistence
Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable clinical success in B cell malignancies. However, its efficacy in solid tumors remains limited, in part due to suboptimal expansion, persistence, and restrained effector function. Strategies that promote durable CAR-T cell fitnes...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
19 March 2026
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| In: |
Cells
Year: 2026, Volume: 15, Issue: 6, Pages: 1-23 |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells15060547 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.3390/cells15060547 Verlag, kostenfrei, Volltext: https://www.mdpi.com/2073-4409/15/6/547 
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| Author Notes: | Zhehong Cheng, Henning Kirchgessner, Beate Jahraus, Emre Balta and Yvonne Samstag |
| Summary: | Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable clinical success in B cell malignancies. However, its efficacy in solid tumors remains limited, in part due to suboptimal expansion, persistence, and restrained effector function. Strategies that promote durable CAR-T cell fitness are therefore required to overcome these barriers. In this study, we generated HER2-CAR-T cells targeting human breast cancer cells and evaluated the impact of different cytokine supplementation strategies on CAR-T cell phenotype and function. We analyzed gene expression patterns and performed repetitive tumor killing assays to assess the ability of CAR-T cells expanded with IL-2 + IL-7 + IL-15 compared with IL-2 alone to maintain proliferation and cytotoxic function across multiple rounds of tumor cell exposure. Compared with IL-2 alone, supplementation with IL-7 and IL-15 significantly enhanced CAR-T cell expansion, preserved stem cell-like features prior to antigen encounter, and promoted superior proliferative capacity. Moreover, CAR-T cells cultured with IL-7+15 or IL-2+7+15 maintained sustained cytotoxicity and exhibited increased antitumor cytokine production during repeated tumor challenges. Notably, IL-7 and IL-15 supplementation induced a CD57+ CAR-T cell population that, unlike the immunosenescent CD57+ cells reported previously, retained full proliferative and cytotoxic capacity, with CD57 expression being dynamically downregulated upon antigen stimulation. Collectively, these findings demonstrate that incorporation of IL-7 and IL-15 into CAR-T cell manufacturing protocols substantially improves expansion, persistence, and effector function, supporting their use as a strategy to enhance CAR-T cell performance against solid tumors. |
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| Item Description: | Veröffentlicht: 19. März 2026 Gesehen am 23.04.2026 |
| Physical Description: | Online Resource |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells15060547 |