Insights from ASCO GI and the Future of CAR T-Cell Therapy in Solid Tumors

Robert L. Ferris, MD, PhD

Lineberger Distinguished

Professor

Executive Director

UNC Lineberger Comprehensive Cancer

Center and Chief of Oncology Services

UNC Health System

Chapel Hill, NC

The recent American Society of Clinical Oncology Gastrointestinal (GI) Cancers Symposium in San Francisco, California, presents an important update of this heterogeneous group of cancers and novel therapies and combinations for a generally immune-resistant set of cancers. Although esophageal and gastric cancer as well as mismatch repair– deficient and microsatellite instability–high colorectal variants present immune responsive subsets where immune checkpoint inhibitor alone or in combination with neoadjuvant chemotherapy may yield dramatic benefit, others such as hepatocellular carcinoma or BRAF-mutated colorectal cancer may benefit from multikinase-targeted inhibitors.

Exciting data analyses suggest early- or long-term results across settings. Given that our understanding of the biology of subsets has improved but is not universally settled, the field is challenged to continue segregating subsets by genomic or targeted dependencies. New multiomics strategies should enable insights with the appropriate specimens and clinical trial designs.

[Looking ahead to our coverage next issue] the European Hematology Association/ European Bone Marrow Transplant 7th Chimeric Antigen Receptor (CAR) T-Cell Meeting provides the frontier for gene-modified cellular therapies extending beyond hematologic malignancies into the rapidly growing experience in solid tumors. With the recent approval of tumor-infiltrating lymphocyte therapy for melanoma, gene-modified autologous cell strategies including CAR T-cell approaches present an innovative strategy to expand the cellular substrate for longevity and tumor-specific targeting.

At present, this is a laborious and cumbersome exercise, developing vectors and CAR treatments that target the tumor selectively with limited toxicity at the normal tissue interface. As we gain greater experience with the affinity of the CAR for the target itself and the expression profile in various solid tumors, innovative strategies are emerging. Given the 5 or more hematologic cancers with approved cell therapies, we can expect future novel cellular approaches and clinical trials with extended clinical end points rather than simply first-in-human or toxicity questions being resolved. Further, work will be needed to integrate them into the standard-of-care regimens.

In the meantime, it is exciting to see the CAR T-cell field move into the solid tumor realm and is a welcome development.