CAR-T Shows Promise and Challenges in Autoimmune Disease

Roberto Caricchio has devoted nearly thirty years to studying lupus, observing the gradual advancements in understanding and treating this intricate autoimmune disease. However, recent years have seen a remarkable shift thanks to groundbreaking research by German scientists demonstrating that cellular medicines can drive lupus into remission in ways other drugs cannot. This progress has generated significant industry interest, leading to the initiation of numerous clinical trials, with many more on the horizon.

Caricchio, who heads UMass Chan Medical School's rheumatology department, describes these developments as unprecedented and sometimes overwhelming. This progress was prominently featured at a recent European Alliance of Associations for Rheumatology meeting in Austria, where leading scientists and physicians in autoimmune disease research gathered. Georg Schett, from Friedrich Alexander University, Erlangen-Nurnberg, Germany, presented new data showing that cell therapy continues to benefit almost all treated participants with various autoimmune conditions, with some remissions lasting up to three years.

Schett expressed his excitement, noting that when his team began this journey three years ago, they were unsure of its direction. Numerous companies, such as Kyverna Therapeutics, Cabaletta Bio, and Novartis, are building on Schett's findings. They provided updates on their clinical studies of CAR-T therapies for lupus and other autoimmune conditions, including myositis and systemic sclerosis.

These new results, though from small clinical trials, mark the early stages of a potentially long journey to demonstrate that treatments engineered from a patient’s own cells can rewire the immune systems of people with inflammatory diseases. For instance, Cabaletta reported that one of the first two individuals treated with CAR-T no longer needs other drugs, while the second is reducing steroid use. Kyverna shared similar outcomes in six of seven lupus patients, some treated over six months ago. Another patient with myasthenia gravis has gone a year without signs of disease or the need for other medications.

Kyverna's CEO Peter Maag emphasized that their work is helping to shape the understanding of immune system resets. Novartis and other biotechs, including iCell Gene Therapeutics and JW Therapeutics, also reported positive responses to CAR-T in their trials. Participants generally experienced mild immune and neurological side effects, a relief to researchers as patients with autoimmune diseases have lower risk tolerance compared to those with fatal cancers.

Before starting testing in 2021, the potential for severe safety issues was a significant concern. However, Schett, who advises Kyverna and Cabaletta, now feels more confident. Despite this, existing treatments for autoimmune diseases set a high bar for the introduction of cell therapy, which remains costly, complex to manufacture, and largely limited to specialized centers. Long-term health issues, such as secondary malignancies observed in some cancer patients treated with CAR-T, remain a concern.

Daniel Wallace, chief of rheumatology at City of Hope and Cedars Sinai Medical Center, remains cautious, suggesting that cell therapy should not be a first-line treatment. He emphasizes that such therapies are worthwhile only if they can induce long-term remission in patients with life-threatening conditions. Analysts are closely monitoring whether these therapies can reduce the need for immunosuppressive drugs. Though some relapses have been reported, the overall responses have been promising.

Cabaletta's CEO Steven Nichtberger acknowledged that while there will be side effects and treatment failures, the goal is to achieve outcomes that are as good as or better than current therapies. There are still many unanswered questions, especially regarding the treatment’s effectiveness in Black patients and those with severe kidney damage. Moreover, while infections observed in trials have been mild, they remain a concern.

Personalized cell therapies are being joined in clinical trials by donor cell-based treatments, natural killer cells, and dual-targeting antibody drugs called T cell engagers. These alternatives are seen as more convenient and potentially easier to manufacture, potentially challenging the dominance of CAR-T therapy. This trend mirrors the oncology field, where the initial enthusiasm for CAR-T has been tempered by successes with other technologies.

Caricchio believes the next decade could be transformative for both physicians and patients, as these advancements continue to evolve.