Dr Hecht on Barriers to CAR T-Cell Therapy Treatment in Solid Tumors

J. Randolph (Randy) Hecht, MD, professor, clinical medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), director, UCLA Gastrointestinal Oncology Program, discusses barriers to treatment with CAR T-cell therapy in patients with solid tumors, highlighting various efforts that investigators are spearheading to address these unmet needs.

Oncologists have maintained a longstanding interest in cellular therapies for patients with solid tumors, Hecht begins. Promising outcomes with CAR T-cell therapies have emerged in patients with hematologic malignancies, Hecht explains, citing that patients with B-cell malignancies are experiencing enduring benefits with this treatment approach.

Historically, investigators have expanded their exploration of cellular therapy into the solid tumors realm, revealing multiple significant challenges among these investigations that indicate the limited efficacy of CAR T-cell therapy, Hecht expands. He adds that these treatments often result in on-target, off-tumor toxicities, which can be a problematic combination. However, investigators hypothesize that these efficacy and tolerability challenges may be interconnected because in hematologic malignancies, a highly suitable target in the form of CD19 exists, which is present on both malignant cells and dispensable cells, he notes.

For example, the challenge with using CAR T-cell therapy in the gastrointestinal tract is the scarcity of dispensable organs, Hecht continues, stating that beyond the appendix, most organs in the GI tract are essential. Although a cellular therapy might be effective in targeting a tumor-associated antigen, problems then arise from the presence of numerous normal cells that express the same target, he emphasizes. However, despite these unmet needs within the solid tumor treatment landscape, researchers have explored various approaches to circumvent these challenges. Tumor-infiltrating lymphocytes and T-cell receptors have shown promise in patients with solid tumors in isolated, anecdotal instances, but there have also been instances where cellular therapy programs in solid malignancies were discontinued because of a combination of ineffectiveness and severe toxicities, Hecht says. Overall, these unmet needs with CAR T-cell therapies in patients with solid tumors remain to be addressed.