{"publisher":{"name":"MDPI","@type":"Organization"},"@type":"ScholarlyArticle","name":"Boosting the Activity of Melanoma-Targeting CAR-T Cells in the Presence of Citrate by the Application of Gluconate","keywords":"CAR-T cell; adoptive T cell therapy; gluconate; citrate; melanoma; tumor\r\nmicroenvironment, 610 Medizin","url":"https://epub.uni-regensburg.de/79407/","description":"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.","@context":"http://schema.org/","datePublished":"2026","creator":[{"@type":"Person","name":"Dennis Christoph Harrer","givenName":"Dennis Christoph","@id":"http://orcid.org/0000-0001-7512-572X","familyName":"Harrer"},{"@type":"Person","name":"Sebastian Haferkamp","givenName":"Sebastian","@id":"http://orcid.org/0000-0002-3894-8345","familyName":"Haferkamp"},{"givenName":"Wolfgang","name":"Wolfgang Herr","@type":"Person","familyName":"Herr"},{"familyName":"Mycielska","@type":"Person","name":"Maria E. Mycielska","givenName":"Maria E.","@id":"http://orcid.org/0000-0001-5222-256X"},{"familyName":"Dörrie","givenName":"Jan","name":"Jan Dörrie","@type":"Person"},{"familyName":"Schaft","name":"Niels Schaft","givenName":"Niels","@type":"Person"},{"familyName":"Abken","name":"Hinrich Abken","givenName":"Hinrich","@type":"Person","@id":"http://orcid.org/0000-0002-4302-3240"},{"@id":"http://orcid.org/0009-0004-6601-6299","name":"Konstantin Drexler","givenName":"Konstantin","@type":"Person","familyName":"Drexler"}]}