Boosting the Activity of Melanoma-Targeting CAR-T Cells in the Presence of Citrate by the Application of Gluconate
Harrer DC, Haferkamp S, Herr W, Mycielska M, Dörrie J, Schaft N, Abken H, Drexler K (2026)
Publication Type: Journal article
Publication year: 2026
Journal
Book Volume: 18
Article Number: 551
Journal Issue: 5
DOI: 10.3390/pharmaceutics18050551
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” 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.
Involved external institutions
Universität Regensburg
Germany (DE)
Universitätsklinikum Regensburg
Germany (DE)
CCC Allianz WERA
Germany (DE)
Bayerisches Zentrum für Krebsforschung (BZKF)
Germany (DE)
Germany (DE)
Universitätsklinikum Regensburg
Germany (DE)
CCC Allianz WERA
Germany (DE)
Bayerisches Zentrum für Krebsforschung (BZKF)
Germany (DE)
How to cite
APA:
Harrer, D.C., Haferkamp, S., Herr, W., Mycielska, M., Dörrie, J., Schaft, N.,... Drexler, K. (2026). Boosting the Activity of Melanoma-Targeting CAR-T Cells in the Presence of Citrate by the Application of Gluconate. Pharmaceutics, 18(5). https://doi.org/10.3390/pharmaceutics18050551
MLA:
Harrer, Dennis Christoph, et al. "Boosting the Activity of Melanoma-Targeting CAR-T Cells in the Presence of Citrate by the Application of Gluconate." Pharmaceutics 18.5 (2026).
BibTeX: Download