Dr Braun on the Current Kidney Cancer Treatment Paradigm

David A. Braun, MD, PhD, assistant professor, medicine (medical oncology), Louis Goodman and Alfred Gilman Yale Scholar, Yale School of Medicine, member, Center of Molecular and Cellular Oncology, Yale Cancer Center, discusses the variety of therapies available for the treatment of patients with kidney cancer, as well as the roles each of these therapies play in enhancing immune responses against the cancer.

Using the analogy of a car filled with T cells, Braun explains that the objective of kidney cancer treatment is to drive the immune system toward the tumor as quickly and accurately as possible. One approach for moving the car forward involves releasing the brakes, which is akin to the mechanism of immune checkpoint inhibitors—the most widely used therapy in kidney cancer, Braun says. Another approach is to press the gas pedal, which is similar to the effect of immune agonists such as cytokine therapies, Braun notes. These therapies have a longstanding history in the management of kidney cancer, and recent advancements have led to the development of engineered cytokines that selectively accelerate immune cells, Braun explains. However, although these strategies help the immune system move faster, they don’t necessarily guide it directly toward the tumor.

This is where a steering mechanism becomes crucial, represented by antigen-directed therapies, Braun continues. By identifying specific markers on tumor cells that the immune system can recognize and target, researchers can direct the immune response precisely where it is needed, according to Braun. This can be achieved through various modalities, including antibody therapies, T-cell engagers, CAR T-cell therapies—particularly allogeneic CAR T cells—and personalized neoantigen-targeting cancer vaccines, he details.

Finally, Braun says it’s important to consider clearing traffic, which involves removing T cell–intrinsic factors, as these are obstacles that hinder the immune system’s progress. Such factors include suppressive myeloid cells and an unfavorable microbiome, which can impede the immune system’s ability to reach and attack the tumor effectively, Braun concludes.