First CAR T-Cell Approval for Skin Diseases Anticipated Within the Year

The first chimeric antigen receptor (CAR) T-cell product to target autoimmune diseases, including those with severe dermatologic manifestations, could be getting closer to approval based on studies showing unprecedented efficacy with acceptable safety profiles.

Aimee S. Payne, MD, PhD, chair of the Department of Dermatology at Columbia University, New York City, indicated that the field is moving quickly based on clinical studies in various forms of lupus as well as other challenging diseases affecting the skin such as pemphigus vulgaris and dermatomyositis.

Payne, speaking at the Annual Atlantic Derm Conference (ADC), foresees an evolution in autoimmune diseases that will mirror the impact that CAR T-cell therapy first documented in patients with hematologic malignancies unresponsive to all other options.

Autoimmune Disease Indication Could Come in 2026

In 2017, the first CAR T-cell product was approved by the FDA, for children and young adults with refractory B-cell acute lymphoblastic leukemia later. If a CAR T-cell therapy is approved for an autoimmune disease within the next 12 months, it will follow a 2021 case report of CAR T-cell treatment in a 20-year-old woman with systemic lupus erythematosus (SLE).

In that report, a serologic remission in the patient, who had refractory SLE involving multiple organs, including the skin, was achieved in about 5 weeks. It was soon followed by clinical remission defined by a SLE Disease Activity Index (SLEDAI) score of zero.



There was no evidence of cytotoxic release syndrome or neurotoxicity and adverse events associated with CAR T-cell therapies, the authors reported.


In a 2024 summary of phase 1 trials in SLE, the efficacy and safety of several different CAR T-cell constructs further supported the promise of CAR T-cell therapy for this indication. In one series of 13 patients that has not yet been published, 11 patients improved within a month with further gains ensued over time. Three patients remained symptom-free off all medication for up to 44 months.

In hematology, the first approved CAR T-cell indication was soon followed by others. For autoimmune diseases, the first indication is likely to be granted to SLE, a disease that often involves cutaneous manifestations. Other autoimmune disorders, such as multiple sclerosis, myasthenia gravis, and Sjogren disease, might follow, but Payne focused on work involving diseases of the skin, such as pemphigus vulgaris and dermatomyositis.

For hematologic malignancies, CAR T cells are engineered to express receptors for antigens on target cancer cells to deliver an antitumor effect. For autoimmune diseases, the CAR-T cells are engineered to express receptors for antigens on autoreactive immune cells aimed at halting autoimmune activity.


Providing a list of nearly 20 CAR T-cell products in or nearing clinical trials in an array of autoimmune diseases, Payne reported that it is unclear at this point which of these products will be the first to be approved. Front runners include mivocabtagene autoleucel (miv-cel), zolacabtagene autoleucel (Zola-cel), rapcabtagene autoleucel (rap-cel), and resecabtagene autoleucel (rese-cel).


All of these and the majority of the other CAR T-cell products under investigation in autoimmune diseases target CD19-positive B cells, but there are other targets, and not all of the CD19-targeted products employ the same transmembrane domain, a co-receptor on the B cell surface. Some products are fully human, others are allogeneic, and at least one involves gene editing, Payne reported.

According to Payne, SLEDAI scores begin to fall within days of CAR T-cell infusion. Peak response is typically achieved within 60 days. It is not yet clear whether CAR T-cell therapy is capable of curing SLE or other autoimmune diseases, but responses are often persistent in the limited follow-up to date.
Benefit Attributed to Immune System Reset

In autoimmune diseases, the benefit of CAR T-cells has been credited to a reset of the immune system. However, Payne cited studies suggesting that preconditioning lymphodepletion prior to delivery of engineered T cells, which is standard in the treatment of hematologic malignancies, might not be required for at least some autoimmune diseases.


For example, she cited unpublished data from a small series of patients with pemphigus vulgaris treated with the rese-cell construct. Despite foregoing lymphodepletion, responses appeared to be similar to those seen when lymphodepletion is used, suggesting that the inherent risks of depleting immune function might be avoided, she said.

“Lots of development programs are now studying protocols that do not involve B cell depletion,” Payne said.

Even if the most encouraging preliminary reports have been in refractory B-cell mediated autoimmune connective tissue diseases, “CAR T-cell therapy could emerge as a treatment breakthrough for difficult-to-treat autoimmune skin diseases as well,” agreed Vishal Gupta, MD, an associate professor in the Department of Dermatology and Venereology, All India Institute of Medical Science, New Delhi, India.

In a recently published review article of the progress in CAR T-cell therapy in dermatology, Gupta, the senior author, and his coauthors, covered the clinical and experimental studies with CAR T-cells using standard and novel designs. He identified progress in developing constructs with greater specificity for specific B cell mediated diseases and CAR T-cells designed to inhibit more specific immune mediators of diseases like pemphigus vulgaris.


One example involves vitiligo, which is linked to overexpression of ganglioside D3 (GD3) as a source of melanocyte dysfunction. In animal models, GD3 CAR engineered T-regulatory cells have improved pigmentation, Gupta and coauthors reported in the review.

So far, the studies in treating skin diseases beyond those mediated by B cells are largely supported by experimental studies, but Gupta said that he believes there is a basis for “cautious optimism.” Yet he cautioned that the field even for the treatment B cell associated autoimmune diseases is not without hurdles.

“Apart from efficacy, concerns regarding treatment toxicity, logistics, accessibility, and cost will need to be addressed before it can be adopted on a larger scale,” he told Medscape Medical News.


Payne reported having financial relationships with Avilar, Cabaletta, and GlycoEra. Gupta reported having no potential conflicts of interest.

https://www.medscape.com/viewarticle/first-car-t-cell-approval-skin-diseases-anticipated-within-2026a1000mmt