Inducible CAR T Cells Target Solid Tumors Better

Chimeric antigen receptor (CAR) T cell therapy harnesses the patient’s immune system to target and destroy cancer cells, offering hope for blood cancers such as leukemia and lymphoma. However, its application in solid tumors has faced significant challenges. In an article published by The Scientist and written by Shelby Bradford, PhD, immunooncologist Shipra Das of Cellectis discusses how her team is using gene-editing technology to overcome these barriers

Traditional CAR T cell development relies on harvesting and modifying a patient’s own T cells. This presents limitations: the patient may have too few viable cells due to illness or prior treatment, and manufacturing is time-consuming less than ideal in fast-moving cancers. Additionally, solid tumours pose a unique challenge, as the suppressive tumour microenvironment (TME) hinders CAR T cell access and activity. Off-target effects also remain a concern, since tumour antigens may appear albeit at lower levels on healthy cells. To address these issues, Das’s team used TALEN gene editing to delete the T cell receptor gene in donor stem cells, producing universal CAR T cells that don’t attack the patient’s own tissue. They then developed a conditional activation system.

By exploiting cancer-associated fibroblasts in the TME, they designed a receptor that responds to a fibroblast protein. Normally, this would trigger a suppressive signal—but they replaced the gene with one encoding a second CAR, active only within the tumor. This IF/THEN-gated logic ensures highly targeted, tumor-specific activity. The system is also modular, allowing flexibility to tailor CAR T cells to different solid tumour types.

Top Image credit: © istock.com, (The Scientist)

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