Dr Hurwitz on the Feasibility of Utilizing CAR T-Cell Therapy in Solid Tumors

Michael Hurwitz, MD, PhD, associate professor, Internal Medicine (Medical Oncology), Yale School of Medicine, discusses the feasibility of utilizing CAR T-cell therapies in patients with solid tumors, such as kidney cancers.

Using CAR T-cell therapies in the realm of solid tumors is associated with greater challenges than using these products in patients with hematologic malignancies, Hurwitz begins. These challenges are primarily attributed to the intricate nature of the solid tumor microenvironment, according to Hurwitz. Unlike liquid tumors that reside in the bloodstream and are easily accessible, solid tumors often present with a more toxic and hypoxic microenvironment, he states. The difficulty lies in reaching these tumors, which may also exhibit increased heterogeneity, Hurwitz adds. CAR T-cell therapies, which are designed to target a specific feature or antigen on tumor cells. When that targeted antigen is lost, these therapies are less effective or entirely ineffective, he notes.

Solid tumors, which are prone to losing specific therapeutic markers, demand careful selection of robust and stable markers, Hurwitz continues. The marker chosen must be abundant on the tumor and resistant to easy loss, a challenging criterion to meet, he says. Another persistent challenge in managing both liquid and solid tumors is the risk of on-target, off-tissue effects, which occur when the targeted antigen that is present on the tumor is also found on healthytissues, Hurwitz explains. This dual presence can result in considerable toxicity, even leading to deaths, as observed in early trials of certain therapies for patients with other diseases, he emphasizes.

For kidney cancer, several issues can arise when targeting markers such as CA9, Hurwitz continues. An initial trial investigating an agent targeting CA9 resulted in overwhelming toxicity, prompting ongoing efforts to refine the approach, he says. Currently, the primary target for kidney cancer is CD70, a well-known and described marker with a history of reliability, Hurwitz says. CAR T-cell therapies are robust killers that surpass previous limitations in specificity and killing ability observed in therapies from earlier treatment eras, Hurwitz concludes.