Novel CAR-T Cell Therapy Trial for Lupus Launched by Atlantic Health System

Mohamed Cherry, MD

Credit: Atlantic Health System

Atlantic Health System recently announced the enrollment of the first US patient in a study designed to explore the safety and efficacy of Chimeric Antigen Receptor (CAR)-T cell for the treatment of lupus.1 The phase 1, multicenter, open-label study will focus on patients with severe, refractory systemic lupus erythematosus (SLE), an autoimmune disease that often results in symptoms such as joint pain and swelling, rashes, fever, fatigue, and damage to the heart, kidneys, brain, and lungs.

Neil Kramer, MD

Credit: Atlantic Health System

In an interview with HCPLive, Mohamed Cherry, MD, medical director of Hematology at Atlantic Health System, and Neil Kramer, MD, a rheumatologist associated with Atlantic Health System and co-founder of the Institute for Rheumatic and Autoimmune Diseases (IRAD), discuss the clinical significance of this inaugural trial and how it addresses the unmet need for effective therapies in patients with refractory lupus.

HCPLive: What motivated Atlantic Health System to explore CAR-T cell therapy as a potential treatment for lupus?

Neil Kramer, MD:Atlantic Health System has been concentrating on cutting-edge research aimed at treating SLE, particularly for patients who haven't responded well to existing therapies. There remains an unmet need for more effective treatments in this patient population. CAR-T therapy has emerged as a promising approach, allowing us to target specific cells of the immune system implicated in lupus. Bristol Myer Squibb, a pharmaceutical company that has developed CAR-T therapy for certain lymphomas and leukemias, reached out to us due to our expertise in CAR-T therapy, and we are now one of several select sites in the US to be studying the efficacy and safety of this therapy in patients with refractory forms of SLE.

Mohamed Cherry, MD: Over the past 5 years, we have developed a strong cellular therapy program, gaining recognition from the community and various pharmaceutical companies. During the COVID-19 pandemic, we were leaders in immunotherapy, exploring innovative approaches to the management of this virus. Our collaboration with pharmaceutical companies has led to us enrolling the first patient in the US for a trial targeting lupus. Having strong cellular therapy and rheumatology research programs has led to the early selection of Atlantic Health System as one of the potential sites for such an important clinical trial. The collaboration between our cellular therapy and rheumatology programs was crucial.

HCPLive: Can you explain the key objectives and design of the phase 1, open-label study?

Kramer:This trial is primarily focused on evaluating safety and, secondarily, effectiveness in treating severe recalcitrant lupus. It involves products that have been approved for hematologic malignancies for several years, yet remains in phase 1 due to its early stages of application in autoimmune diseases. The trial aims to determine the safety and efficacy of these cells, including assessing the appropriate dosage. This requires long-term follow-up. Patients will be monitored monthly for the first 2 to 3 years and will undergo 15 years of follow-up to ensure there are no unexpected long-term side effects from the therapy.

HCPLive: How do autoreactive B cells contribute to the pathogenesis of lupus, and what potential advantages does CD19-specific CAR-T cell therapy offer in addressing this mechanism?

Kramer:The cause of lupus remains unknown, but it's believed to involve a combination of genetic predisposition and environmental triggers. Individuals with specific immunogenetic backgrounds may be triggered by environmental factors, leading to an immune response involving B cells. These cells, crucial for antibody production and immune system communication, are targeted in lupus treatment. Depleting or modulating B cells has shown clinical benefits in managing lupus manifestations. However, complete and sustained remission often requires not only targeting B cells in circulation but also those residing in tissues like lymph nodes and kidneys, where inflammation occurs.

HCPLive: Can you walk us through the process of utilizing CD19-specific CAR-T cells to deplete CD19+ B cells in patients with lupus?

Cherry: CAR-T cell therapy offers a promising approach to targeting B cell lymphocytes implicated in lupus pathogenesis. The process involves identifying suitable patients, isolating specific immune cells, modifying them in the lab to recognize and target B cell lymphocytes, and then administering them back to the patient after chemotherapy. These engineered CAR-T cells act like soldiers, seeking out and eliminating B cells in various tissues, aiming to halt the progression of lupus and restore immune balance.

HCPLive: What are the anticipated outcomes of the study in terms of disease remission and resetting the immune system in lupus patients?

Kramer: The expectations for CAR-T cell therapy in treating lupus are high. Currently, 8 patients treated in Germany are being followed: 3 with polymyositis, 1 with anti-synthetase syndrome, and 1 with Scleroderma, all of which are autoimmune diseases where B cells play a critical role. Of the 8 lupus patients treated, all have responded positively, achieving remission and discontinuing all medication. The longest follow-up is nearly 3 years, with the shortest being 6 months, showcasing significant and drug-free remission, which is remarkable for this disease.

The key question revolves around the duration of these remissions and the potential for recurrence. If recurrence does occur, the availability of stored CAR-T cells raises the possibility of reinfusion and achieving similar results. While expectations are high, it's essential to gather more data through clinical trials to better understand the long-term efficacy and safety of CAR-T cell therapy for lupus.

Cherry: I believe this will open the door for more than just lupus patients. If this turns out to be as successful as we anticipate, then we can tackle other autoimmune diseases, apply the same principle, and hopefully, have the same results.

HCPLive: How does the collaboration between the cellular therapy and rheumatology programs at Atlantic Health System enhance patient care and treatment outcomes in the context of this trial?

Cherry: At Atlantic Health System, we have a centralized research program and tend to collaborate closely. For example, I'm currently collaborating with some cardiologists on stem cell therapy for injecting stem cells into the myocardium to reverse the effects of congestive heart failure. Whenever there is an opportunity, we sit together, study the clinical trial, and assess its feasibility. This collaboration serves as an excellent model for other institutions looking to establish similar programs.

Kramer: From my perspective, it has been wonderful. The study nurses and coordinators from Dr Cherry's division have vast experience with CAR-T, which has been reassuring as we monitor for any potential toxicities.

HCPLive: Is there anything else you would like our audience to know?

Cherry: The work that is being done at the Atlantic Health System speaks volumes of the commitment of our researchers, regardless of which discipline they fall into. This collaboration is crucial and should be successful because, in the end, we are here to serve our patients in the community. This whole thing has been very exciting and we're going to continue to move forward in this region and with future collaborations.

References

1. ^{Atlantic Health System enrolls first U.S. patient in lupus treatment trial. Atlantic Health System: Hospitals Serving New Jersey & New York. February 8, 2024. Accessed March 27, 2024. https://www.atlantichealth.org/about-us/stay-connected/news/press-releases/2024/Atlantic-Health-Lupus-Car-T-Trial.html.}