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      "keywords": "CAR-T cell; adoptive T cell therapy; gluconate; citrate; melanoma; tumor\r\nmicroenvironment",
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      "title": "Boosting the Activity of Melanoma-Targeting CAR-T Cells in the Presence of Citrate by the Application of Gluconate",
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          "name": {
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            "given": "Maria E.",
            "honourific": null
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            "lineage": null,
            "family": "Dörrie"
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          "orcid": null,
          "name": {
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            "given": "Niels",
            "family": "Schaft",
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            "given": "Hinrich",
            "lineage": null,
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          "orcid": "0000-0002-4302-3240",
          "id": "abh27529"
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            "lineage": null
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      "abstract": "Background: Chimeric antigen receptor (CAR) T cells achieve cure in the therapy of hematological malignancies. In solid tumors, however, CAR-T cells face an immunosuppressive tumor microenvironment (TME) which crucially impedes their cytotoxic capacities. Citrate accumulating in the TME is a crucial metabolite in mediating immune suppression and is consumed by cancer cells promoting growth of various tumors, including melanoma; blocking the citrate transporter pmCiC with gluconate abrogates citrate-mediated tumor growth. Methods: To bolster treatment of melanoma, we explored gluconate as adjuvant for CAR-T cell therapy. Results: First, gluconate did not impair CAR-T cell functional capacities with regard to cytotoxicity, cytokine secretion, and persistence in a “stress test”\r\nbased on repetitive antigen stimulation with cognate cancer cells. The addition of gluconate antagonized the citrate-mediated enhanced proliferation of melanoma cells. As a consequence, the elimination of citrate-boosted melanoma cells by CSPG4-specific CAR-T cells was augmented in the presence of gluconate. Conclusions: Taken together, these data suggest that counteracting citrate-mediated enhanced tumor growth with gluconate may improve the cytotoxic activity of CAR-T cells against melanoma.",
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