Dr Koehne on Efforts to Overcome CAR T-Cell Resistance in Hematologic Malignancies

Guenther Koehne, MD, PhD, deputy director, chief, Blood and Marrow Transplant, Hematologic Oncology, Benign Hematology, Miami Cancer Institute, Baptist Health, discusses the continued exploration of novel approaches that are taking place to overcome resistance mechanisms in hematologic malignancies, specifically in patients who may not respond optimally to initial CAR T-cell treatment.

Resistance to CAR T-cell therapies may arise from several factors, including insufficient expression of target molecules on tumor cells and mechanisms allowing tumors to evade immune detection, such as downregulation of targeted antigens, Koehne begins. These challenges can lead to disease recurrence without the expression of the originally targeted marker, he adds.

To address these issues, researchers are exploring innovative strategies to enhance the efficacy of CAR T-cell therapies, Koehne states. One promising approach involves the use of bispecific CAR T-cells, which simultaneously target multiple antigens on cancer cells, Koehne details. For example, an ongoing clinical trial led by Dr. Koehne and his colleagues at the Miami Cancer Institute is investigating CAR T-cell therapy targeting both CD19 and CD20 or CD19 and CD22 in lymphoma.

By targeting multiple antigens on tumor cells, bispecific CAR T-cells aim to overcome resistance mechanisms and reduce the risk of disease recurrence in early stages of disease, Koehne notes. This strategy offers a more comprehensive approach to tumor targeting, potentially enhancing therapeutic responses and prolonging remission in patients with hematologic malignancies, he emphasizes.

Overall, the development of bispecific CAR T-cell therapy may represent the next generation of CAR T-cell therapies, offering the potential to overcome resistance and improve treatment outcomes. Continued research in this area is crucial to optimize CAR T-cell therapies and broaden their applicability across various cancer types. With further investigation and refinement, bispecific CAR T-cells may become an integral component of personalized cancer treatment strategies, ultimately benefiting patients with resistant or recurrent disease, Koehne concludes.