Dr Leick on Limitations Associated With CAR T-Cell Therapy in Hematologic Malignancies

Mark Leick, MD, physician investigator, CCR Group C Monthly, Massachusetts General Research Institute, assistant professor, medicine, Harvard Medical School, assistant in medicine, Medicine-Hematology/Oncology, Massachusetts General Hospital, discusses the challenges and limitations associated with the use of CAR T-cell therapy across hematologic malignancies, highlighting how ongoing research may potentially ameliorate present unmet needs.

The development of CAR T-cell therapy has become a unified endeavor, with multiple companies dedicating resources to this field, Leick begins. However, the logistical aspects of administering this therapy poses a significant challenge, he says. CAR T-cell therapy is custom-manufactured for individual patients, with the exception of some clinical trials. This process involves collecting the patient's T-cells, sending them for manufacturing, and then returning them for subsequent treatment, Leick details. The variation in T cell behavior can present a substantial challenge. Moreover, the costs involved in manufacturing CAR T-cell therapy can create difficulties in terms of payments and insurance approval, Leick adds.

Another limitation with the use of CAR T-cell therapy lies in extending its use to other disease types, Leick continues. Although efforts are underway to address this need, the therapy has not yet proven as effective when treating solid tumors, Leick explains. Nonetheless, advancements in this area could yield positive outcomes in the near future, Leick says. Notably, investigators at Stanford University have achieved promising results by using CAR T-cell therapy to treat diffuse intrinsic pontine glioma, a pediatric brain tumor, he describes, adding that further research and collaboration are necessary to achieve this outcome, Leick states.

Lastly, researchers are striving to develop allogeneic CAR T-cell products that can be readily administered to patients without customization-related manufacturing delays, Leick says. This approach could resemble the current model of blood donation, where standardized products can be readily used, Leick continues. The use of modern genetic technologies to prevent complications such as cross tolerance and graft-vs-host disease could increase the efficacy of allogeneic CAR T-cell therapies across a broader group of individuals. Although progress is being made, additional work and refinement are needed to overcome these obstacles and make allogeneic CAR T-cell therapy a viable option, Leick concludes.