CAR-T Cells in Solid Tumors: Overcoming Resistance Mechanisms for Effective Therapy

In a recent article published in “Die Innere Medizin” (German), LIT scientists Dr. Markus Barden, Dr. Astrid Holzinger, and Prof. Hinrich Abken comprehensively review the challenges and emerging solutions for chimeric antigen receptor (CAR) T cell therapy in solid tumors. This overview is especially important for oncologists, immunologists, and medical researchers interested in cellular therapies against cancer.

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Date Published

September 15, 2025

CAR-T cell therapy modifies a patient’s own T cells to express synthetic receptors that selectively target tumor cells. While this therapy has revolutionized treatment for certain blood cancers, its application in solid tumors has been disappointing due to complex resistance mechanisms.

Solid tumors often display mixed expression of target antigens, causing some tumor cells to evade CAR-T detection and survive. The dense tumor stroma and abnormal blood vessels limit CAR-T cell migration into tumors. Solid tumors create hostile conditions for T cells, including low oxygen, high acidity, nutrient deprivation, and immunosuppressive factors. Maintaining CAR-T cell function over time in tumors remains difficult.

Despite these challenges a promising next-generation approach uses CAR-T cells engineered as “biopharmaceutical factories” (TRUCKs) that locally release therapeutic cytokines upon tumor recognition. This not only kills cancer cells directly but also activates natural killer cells and macrophages, amplifying overall anti-tumor immunity.

The authors highlight the ongoing development of allogeneic (“off-the-shelf”) CAR-T cells to reduce costs and expand accessibility, as well as the need for improved biomarker-based patient selection to tailor CAR-T therapies. Despite remaining challenges, these innovative strategies point toward making CAR-T therapy an effective option for solid tumors.