Building on Mouse Model
Dr. Schett and his team, building on these foundational findings, moved the approach to the clinical arena. In August 2021, they published a report of a 20-year-old woman with severe refractory SLE treated with autologous CD19 CAR-T cells who experienced rapid remission of her disease.2 This was followed by a small case series in which patients treated with anti-CD19 CAR-T cells showed a reduction of lupus features, including presence of autoantibodies, nephritis and other manifestations. Four of the five study participants saw a reduction of their SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score to 0, and all five were able to stop taking immunosuppressant therapy. About 100 days after CAR-T cell therapy, B cells remained, although symptoms of lupus were absent.
An Immune System Reboot?
From these clinical study results, there is some hope, the researchers agree, that the patients’ immune systems were reset by the therapy. How lasting that effect will be remains to be determined. Dr. Schett has now embarked on an effort to determine whether some self-reactive B cells remain in patients’ tissues. This, of course, could result in continued immune system malfunction. His Lupus Insight Prize award will be used to obtain tissue samples to assess the extent of B cell depletion.
The LRA funding will allow the team to assess patients sequentially and to compare their B cell depletion trajectory with other patients on rituximab. Dr. Schett also notes that patients in the case study have been eager to sign up for this second part of the study. The fast feedback on B cell depletion is reassuring for the patient, and the other component for participation is that they believe they are contributing to better understanding of this therapy.
As a provider, Dr. Schett sees this type of therapy as a paradigm shift, especially for patients with very severe and refractory disease. “The idea that you can actually reset the immune system and not just suppress it is something new and revolutionary. I think the CAR experience tells us that this is at least possible in some patients.”
‘Endless Possibilities’
Dr. Radic notes that the findings of the CAR-T studies open up a wide range of additional questions to be explored—for example, what other cell types, targets and biological functions beyond cytotoxicity could be brought to bear in the fight to curb autoimmune diseases. The Radic lab intends to use the award to learn more about the inner working of CAR T cells.
