CAR-T Cell Therapy for Autoimmune Skin Diseases
The first CAR (chimeric antigen receptor) T-cell therapy related to autoimmune diseases, which relates to skin diseases, could potentially receive approval within the next year! Early clinical trials have shown promising early clinical outcomes, where many patients who received the treatment were able to achieve long-lasting remission.
This was spoken about at the Annual Atlantic Derm Conference (ADC) in New York, where Aimee S. Payne, MD, PhD, Chair of the Department of Dermatology at Columbia University, explained that this field of research is advancing quickly. Trials are currently testing CAR T-cell therapy in autoimmune diseases like:
- systemic lupus erythematosus (SLE)
- pemphigus vulgaris,
- and dermatomyositis.
According to Dr Payne, CAR T-cells have the capability to change autoimmune disease treatment in a similar way that they changed the treatment of certain blood cancers.
The first CAR T-cell treatment was approved by the US FDA back in 2017 to treat children and teenagers with treatment-resistant B-cell acute lymphoblastic leukaemia. Now, experts predict that the approval could come in within the next 12 months. The first disease to be treated would be systemic lupus erythematosus (SLE).
Curiosity regarding this treatment grew after a case back in 2021 where a 20-year-old woman with severe SLE, with skin and multiple organs affected. After receiving CAR T-cell therapy, she achieved serologic remission, after which a complete remission was observed. More importantly, she experienced only mild cytokine-release syndrome and no immune effector cell-associated neurotoxicity, which are two potential side effects of CAR T-Cell therapy.
So what exactly is CAR T-cell therapy? It involves the usage of the patient’s own T-Cell, which will be further genetically engineered in order to recognise specific targets before being reintroduced into the body.
In Cancer, specifically Blood Cancer, the treated cells attacked Cancer cells. However, in autoimmune diseases, the immune system is attacking the body’s own healthy tissues by mistake. Certain B cells, especially those carrying the CD19 marker, produce harmful antibodies that drive diseases like lupus and pemphigus vulgaris. The engineered CAR T-cell targets and destroys these abnormal CD19-positive B cells. By removing the cells causing the autoimmune attack, the immune system can “rebuild” itself with healthier B cells.
Currently, up to 20 CAR T-cell therapies are in or approaching clinical trials for autoimmune diseases. Some of the candidates include:
- mivocabtagene autoleucel (miv-cel)
- zolacabtagene autoleucel (Zola-cel)
- rapcabtagene autoleucel (rap-cel)
- and resecabtagene autoleucel (rese-cel)
While most of them target CD19-positive B cells, they vary in design, with some using allogeneic cells or gene-editing technologies.
Researchers are also studying CAR T-cell therapies for other skin diseases such as pemphigus vulgaris and dermatomyositis.
Payne emphasised unpublished findings which show patients with pemphigus vulgaris treated with rese-cel achieved a similar response without undergoing lymphodepletion, which is a standard pre-treatment used before CAR T-cell therapy in blood cancers.
Another Professor, Dr Vishal Gupta, MD, Associate Professor at the All India Institute of Medical Sciences (AIIMS), New Delhi, believes CAR T-cell Therapy could become a ground-breaking research for difficult-to-treat autoimmune skin diseases. Dr Gupta and his coworkers explained that experimental research for vitiligo, where GD3 CAR-engineered regulatory T cells improved skin pigmentation in animal models.
Though the results have shown to be promising, experts advise that larger clinical trials are needed to be done to ensure the long-term safety and efficacy of the treatment. Challenges like treatment toxicity, logistics, accessibility, and cost must also be addressed before this therapy can become widely available.
Even so, the rapid progress seen suggests that CAR T-cell Therapy may soon become a future option for patients with skin autoimmune disease.
