榴莲视频

SAN DIEGO -- Chimeric antigen receptor (CAR) T-cell therapy increasingly looks like the next big thing in autoimmune rheumatic disease (ARD) therapy, with new reports here continuing to demonstrate positive results, and with Big Pharma now muscling in.

At the American College of Rheumatology's annual meeting, the leading pioneer of this approach in ARD provided an update on his group's expanding program, which now includes 15 patients with different diagnoses, all of whom had achieved long-lasting complete remission -- and, moreover, did so without losing vaccine-induced immunities.

Meanwhile, a research team assembled by Novartis reported a pilot study in which its investigational CAR-T product first developed for chronic lymphocytic leukemia (CLL), , appeared effective in three patients with systemic lupus erythematosus (SLE).

Both approaches use CAR T-cell technology to induce temporary "deep depletion" of B cells responsible for autoantibody production by targeting the CD19 antigen. The expectation, thus far realized, is that these rogue B cells don't come back after reconstitution.

Georg Schett, MD, and his team at Friedrich Alexander University in Erlangen-Nuremberg, Germany, have been the most prominent in pursuing the new technology using their own home-brewed CAR-T therapy. In achieving a virtual lupus cure in one patient. The number grew to five the following year, and then seven earlier in 2023 (along with two additional patients with anti-synthetase syndrome).

Now Schett and colleagues have reported on a total of 15 patients who had at least 6 months of follow-up after the single-dose treatment -- eight with SLE, three with idiopathic inflammatory myopathies (IIM), and four with systemic sclerosis. All but one of the lupus patients showed complete or nearly complete eradication of all six major autoantibody species (the exception still had persistent anti-nucleosome antibodies but none of the other five). Findings were similar for the IIM and systemic sclerosis patients.

That was not the main point of the group's presentation, however. Rather it was to examine whether patients had kept their immunity to infections for which they had received standard vaccines such as MMR and COVID-19.

Titers of vaccine-induced antibodies remained at or near baseline levels in most patients, and in no case did it appear that antibody-mediated immunity would be lost altogether. (Schett and colleagues didn't analyze actual infections or other markers of immunity besides antibody titers.)

Also, five patients among the 15 received vaccines after their CAR T-cell treatment, including for COVID-19, pneumococcus infection, and tetanus. All showed relatively normal antibody responses when tested afterwards.

Novartis Joins the Hunt

The company is sponsoring a multinational, open-label , also called YTB323, in patients with severe SLE that resisted conventional therapy. Eventually the company hopes to enroll 27 patients (completion is expected in late 2026); this preliminary report covered just the first three. As with most such early-stage studies, the main focus was on safety, but efficacy data were provided as well. Lead author on the report was Josefina Cortés Hernández, MD, PhD, of Vall d'Hebron University Hospital in Barcelona, Spain, but most co-authors were Novartis employees.

All three participants experienced some degree of cytopenia in the first weeks after treatment, severe at times, but all survived with no serious long-term effects.

Efficacy data including lab markers and clinical assessment with the updated SLE Disease Activity Index (SLEDAI). Results in these initial patients mirrored those seen in the Friedrich Alexander program. Autoantibody titers plummeted quickly and C3/C4 complement levels increased; SLEDAI scores also fell markedly from baseline levels of 12-22, reaching zero in one patient. Follow-up was only 28-92 days as of this report, however, making it impossible to judge the effect's durability.

These results were favorable enough that future studies are warranted, according to the authors. Meanwhile, ClinicalTrials.gov lists ongoing early-stage trials in lupus sponsored by a and by two small U.S.-based startups, and . A host of CAR-T trials involving different ARDs are also underway in China.