Off-The-Shelf CAR T Therapy Elicits Responses in Large B-Cell Lymphoma

Treatment with cemacabtagene ansegedleucel (cema-cel) demonstrated responses in patients with relapsed or treatment-resistant large B-cell lymphoma, according to information from a phase 1 trial which were shared in a news release from Allogene Therapeutics, Inc; data on the investigation were also published in the Journal of Clinical Oncology.

The "off-the-shelf" CAR T-cell therapy elicited an overall response rate of 58% and complete response rate of 42% in patients enrolled on the study, and many patients who achieved complete remission remained cancer-free for over two years; the median overall survival has not yet been reached.

In an interview with CURE®, Dr. Frederick L. Locke, expanded on how cema-cel compares with currently available CAR T-cell therapies in terms of effectiveness and safety for patients with relapsed/refractory large B-cell lymphoma. Locke, who serves as chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center and Research Institute, in Tampa, Florida, also explained the mechanism of action of the agent.

Transcript:

Cema-cel is an allogeneic CAR-T cell therapy, so it's coming from healthy donors, and that's different than the CAR-T cell therapies that are currently FDA approved. With the FDA-approved CAR-T cell therapies for large B-cell lymphoma, the T cells are coming from the patient; the T cells are removed from the patient's blood. T cells recognize infected cells or foreign things, and with autologous CAR-T cell therapy, a gene is put in the patient's own cells to reprogram them against CD-19, which is a protein on the surface of the cancerous B cells. Then, the cells are infused back into the patient, where they know where to go and what to do. They then attack and destroy the cancerous B cells.

With cema-cel, it's the same concept of reprogramming using the chimeric antigen receptor [CAR], but instead of using the patient's own T cells, we use donor cells. Those donor cells not only express the CAR against CD-19, but they also have gene editing to remove several genes and proteins within the donor cells. One is CD-52 which is simply a cell surface protein on many immune cells in the body, and that allows us to use a monoclonal antibody to reduce the normal immune cells transiently. This lets that allogeneic donor cells get in and expand. Also, something called the TRAC locus removes the T cell receptor from the donor cells. That T cell receptor is what tells the T cell where to go and what to do. By removing that from the donor cells, we prevent the donor cells from recognizing the patient's body as abnormal or foreign, so we don't have graft-versus-host disease.

Transcript was edited for clarity and conciseness.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.