Science Highlights
Published on November 13, 2025
Glutamine deprivation and efficacy of BCMA-CAR T-cell therapy in MM
by Blood
Navarro F, Lozano T, Fuentes-García A, et al. Reprogramming Glutamine Metabolism Enhances BCMA-CART Cell Fitness and Therapeutic Efficacy in Multiple Myeloma. Blood. 2025; (doi: 10.1182/blood.2024027496).
Researchers suspect that glutamine dependency, a key metabolic feature of multiple myeloma (MM), contributes to the limited efficacy of chimeric antigen receptor (CAR) T-cell therapy in oncology patients. Cancer cells absorb glutamine as a primary energy source, drawing down its levels within the surrounding tumor microenvironment. The subsequent state of glutamine deprivation has the effect of weakening anti-tumor T-cell functionality and supporting immune escape. To address sensitivity to low glutamine concentration observed in anti-BCMA murine CAR T cells, investigators engineered cells to overexpress the glutamine transporter Asct2. The result was better metabolic fitness and anti-tumor efficacy as demonstrated in murine models of MM, which improved mouse survival. In patients, lower levels of Asct2 on MM cells were associated with unfavorable outcome to combined immunotherapy and BCMA-CAR T-cell treatment. The findings suggest that by essentially reprogramming glutamine metabolism, anti-tumor CAR T-cell functionality in the setting of MM may benefit.
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