Is cancer treatment also a cure for lupus?

Autologous chimeric antigen receptor T cell (CAR-T) therapy. took the world of oncology by storm Preliminary results in a handful of patients have recently suggested that it could potentially revolutionize the treatment of systemic lupus erythematosus (SLE).

According to Georg Schett, M.D., Ph.D., Friedrich-Alexander University Erlangen-Nuremberg, Germany, and colleagues, of five patients who received a single dose of CAR-T cell therapy, all five within three months. achieved remission.

Additionally, all five remained in remission without the need for other medications through up to 12 months of follow-up after treatment, the researchers said. reported in natural medicine.

“[T]These data offer new therapeutic possibilities to control SLE disease activity via genetically engineered autologous cells,” write Schett and colleagues, although more patients may be They point out that longer-term follow-up is necessary.

CAR-T cell therapy involves extracting a patient’s T cells via leukapheresis and using viral vectors to transform them and target receptors that bind to specific antigens on other cells that need to be eliminated. express somatic proteins. These transformed T cells are re-infused into the patient to hunt down and kill target cells.

For lupus, and for most forms of cancer currently applied, the target is the B cell. Current oncological indications include hematological malignancies involving malignant B cells such as lymphoblastic leukemia and non-Hodgkin’s lymphoma. This treatment “completely depletes” the B cells, allowing them to return to normal activity when the cell population recovers. (We are working on that as well. Find applications in other targets and solid tumors.)

Since B cells play a powerful role in SLE, the idea that CAR-T cell therapy could be effective in this disease has been raised by many research groups around the world.And last year, Shet’s group reported in New England Journal of Medicine A 20-year-old woman who had failed to respond to all other available treatments, including the anti-B-cell drug rituximab (Rituxan), achieved complete remission in about a month with this treatment.

That experience prompted researchers to try this approach in more patients. In the current study, the patients were all very young (18-24 years old) and 4 out of 5 were female. Baseline scores on the SLE Disease Activity Index-2K (SLEDAI-2K) ranged from 8 to 16 (on a scale of 0 to 105). All had skin and renal involvement, and four also had joint involvement. Belimumab (Benlysta) failed in all five, as did corticosteroids, hydroxychloroquine, and mycophenolate mofetil. Other drugs used in some patients included rituximab, cyclophosphamide, and azathioprine.

Each patient received T-cell extraction with ex-vivo transformation to target the CD19 antigen on B cells and a lymphodepletion regimen with fludarabine and cyclophosphamide. The dose of CAR-T cells was 1 million cells per kilogram of body weight. Within a week, B-cell counts in all five patients dropped to zero and remained there until day 30. Other immune cell counts also plummeted, but recovered in two to three weeks.

Virtually all signs of lupus activity disappeared, just as Shett and colleagues had hoped. SLEDAI-2K scores were assessed 3 months after dosing, reaching zero in four patients and reaching 2 in his one patient whose baseline score was 16. Proteinuria also disappeared.

Perhaps most importantly, antibodies to double-stranded (ds) DNA were also zero in all five patients. “Autoantibodies to dsDNA are also typically reduced by conventional therapy, but seroconversion is rare. showed a decline in ,” exclaimed the researcher.

B-cell populations eventually recovered in line with the decline in CAR-T cell numbers, but this was not accompanied by recurrence of SLE symptoms or biomarkers, including anti-dsDNA antibodies.

Treatment-related adverse effects were mild to non-existent. Cytokine release syndrome (CRS) and associated neurotoxic effects are seen in cancer patients receiving CAR-T cell therapy, but in this study, 3 patients experienced grade 1 CRS; Her two showed no signs of it. None of the patients had an impact on the nervous system. Three patients also had mild fever and two had no fever. No infections occurred.

Clearly, many questions remain about CAR-T cell therapy for SLE. Is it truly a permanent cure or a temporary stopgap measure? Will it be as safe as this pilot study when applied to a larger and more diverse patient population?

Cost could be another issue. Approved CAR-T cell therapies are priced at nearly $400,000, not including costs associated with patient preparation and follow-up. Recent Quote The average cost per cancer patient is approximately $700,000. This could be more than the payer or the patient would be happy with unless it was a real her one-time treatment for lupus.

On the one hand, this early success in SLE may spark interest in applying CAR-T cell therapy to other autoimmune diseases in which B cells play an important role, such as multiple sclerosis. moreover, One review for 2020 Note that this technique could theoretically be applied to targets other than B cells, opening the door to many other disease applications. In fact, a Chinese company called Yake Biotechnology is currently conducting six studies of his CAR-T cell products for autoimmune and other non-cancer diseases. Listed on ClinicalTrials.gov (along with 20 studies of hematologic malignancies).