Dr Qin on the Use of CAR T-Cell Therapy in ccRCC

Qian (Janie) Qin, MD, assistant professor, Division of Hematology and Oncology, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the investigation and use of CAR T-cell therapy in patients with advanced clear cell renal cell carcinoma (ccRCC).

In the field of hematology, CAR T-cell therapy has brought about a profound transformation in the landscape of treatment, yielding remarkable responses, Qin begins. Nevertheless, when it comes to the context of solid tumors, a distinctive array of challenges emerges in the utilization of CAR T-cell therapy, Qin highlights, as T cells are genetically engineered to seek out tumor-associated antigens. An essential requirement of CAR T-cell therapy efficacy is the establishment of a nonclassical immune synapse between CAR T cells and their intended target, she notes. This interaction enables CAR T cells to recognize the presence of tumor cells and subsequently initiate cytotoxic activities, she explains. In the case of solid tumors, however, CAR T cells must overcome a sequence of obstacles, Qin emphasizes.

Initially, CAR T-cells must navigate their way to the tumor site, a journey often involving the traversal of multiple layers of extracellular matrix, Qin expands. Once this is accomplished, they may encounter a hostile tumor microenvironment, she adds. The journey of CAR T-cell therapy to specific regions within the tumor is characterized by a series of challenges and intricate steps, Qin emphasizes.

Another set of challenges revolves around the identification of tumor-associated antigens, she continues. The most favorable tumor-associated antigens are those that exhibit consistent and high levels of expression in tumor cells while remaining absent in normal cells, Qin explains. The presence of these antigens in normal cells could lead to significant autoimmune adverse effects, she says. The process of pinpointing the appropriate tumor-associated antigen for CAR T-cell therapy is of utmost importance, although it may pose a formidable challenge, Qin concludes.