David Porter, MD, on Lessons Learned in Cell Therapy for Autoimmune Disease

“I think one of the things we learned is that toxicity may be more limited in patients with autoimmunity. I also think that clinicians are much better at dealing with the toxicity—in identifying early cytokine release syndrome and being able to intervene early—but I also think the risks look like they're lower than they are in patients with, say, far advanced leukemia or far advanced lymphoma.”

Throughout 2023 and 2024, a number of companies and institutions launched new trials and investigations into the application of cell therapy technology, especially CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy, to the treatment of autoimmune diseases known or thought to be driven by abnormal B-cell activity. Although CD19-directed CAR-T approaches were originally developed for the field of oncology, with the intention of targeting malignant B-cells in diseases like lymphoma, the close association between B-cells and certain autoimmune diseases like lupus made the repurposing of the technology a logical choice for exploration.

To close out 2024, CGTLive® reached out to David Porter, MD, the director of cell therapy and transplant at Penn Medicine, to get his insight on the progress made in these efforts over the past year, and the lessons learned from the experienced gained thus far. Porter highlighted that in the literature reporting on early trials, the vast majority of patients treated with CAR-T for autoimmune disease have achieved some type of response and have been able to come off of their standard immunosuppressive therapy. As such, he stated that this is a very exciting time for the field. Although, he emphasized that the data available is still very limited and early, and more patients and longer follow-up time will be needed before any broad conclusions can be drawn.

Porter also spoke about CAR-T in autoimmune disease from the perspective of safety. He noted that it has been hypothesized that CAR-T in autoimmune disease will carry a lower risk of toxicity than in oncology applications because of the lower antigen burdens involved. Although, Porter also touched on the fact that patients with autoimmune disease generally have a lower risk tolerance for treatment than patients with advanced malignancies, and as such the risks of lymphodepleting chemotherapy, cytokine release syndrome, and neurotoxicities will need to be considered in that context.