{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:22:13Z","timestamp":1792092133420,"version":"4.4.0"},"reference-count":39,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["324392634\u2014TRR221"],"award-info":[{"award-number":["324392634\u2014TRR221"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"award":["324392634\u2014TRR221"],"award-info":[{"award-number":["324392634\u2014TRR221"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Else-Kr\u00f6ner Fresenius Foundation"},{"name":"Helga-Reifert Foundation"},{"name":"Bavarian Cancer Research Center (BZKF) BZKF-Young Scientist Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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 \u201cstress test\u201d based 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics18050551","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:47:28Z","timestamp":1777546048000},"page":"551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Boosting the Activity of Melanoma-Targeting CAR-T Cells in the Presence of Citrate by the Application of Gluconate"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7512-572X","authenticated-orcid":false,"given":"Dennis Christoph","family":"Harrer","sequence":"first","affiliation":[{"name":"Department of Internal Medicine III\u2014Hematology and Internal Oncology, University Hospital Regensburg, 93053 Regensburg, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), 91054 Erlangen, Germany"},{"name":"CCC-WERA, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3894-8345","authenticated-orcid":false,"given":"Sebastian","family":"Haferkamp","sequence":"additional","affiliation":[{"name":"CCC-WERA, 91054 Erlangen, Germany"},{"name":"Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Herr","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III\u2014Hematology and Internal Oncology, University Hospital Regensburg, 93053 Regensburg, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), 91054 Erlangen, Germany"},{"name":"CCC-WERA, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mycielska","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Institute of Biophysics and Physical Biochemistry, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3478-0741","authenticated-orcid":false,"given":"Jan","family":"D\u00f6rrie","sequence":"additional","affiliation":[{"name":"Bavarian Cancer Research Center (BZKF), 91054 Erlangen, Germany"},{"name":"CCC-WERA, 91054 Erlangen, Germany"},{"name":"Department Dermatology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Comprehensive Cancer Center Erlangen European Metropolitan Area of Nuremberg (CCC ER-EMN), 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum Immuntherapie (DZI), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8236-9298","authenticated-orcid":false,"given":"Niels","family":"Schaft","sequence":"additional","affiliation":[{"name":"Bavarian Cancer Research Center (BZKF), 91054 Erlangen, Germany"},{"name":"CCC-WERA, 91054 Erlangen, Germany"},{"name":"Department Dermatology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Comprehensive Cancer Center Erlangen European Metropolitan Area of Nuremberg (CCC ER-EMN), 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum Immuntherapie (DZI), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4302-3240","authenticated-orcid":false,"given":"Hinrich","family":"Abken","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Immunotherapy, Division Genetic Immunotherapy, Regensburg, and Chair Genetic Immunotherapy, University Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6601-6299","authenticated-orcid":false,"given":"Konstantin","family":"Drexler","sequence":"additional","affiliation":[{"name":"CCC-WERA, 91054 Erlangen, Germany"},{"name":"Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Connor, C., Carr, Q.L., Sweazy, A., McMasters, K., and Hao, H. 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