(This is an excerpt of the Health Rounds newsletter, where we present latest medical studies on Tuesdays and Thursdays.)
By Nancy Lapid
June 5 (Reuters) – We also highlight a series of promising CAR-T studies in a variety of hard-to-treat rheumatology disorders.
CAR-T CELL THERAPY PERMITS KIDNEY TRANSPLANT IN HARD-TO-MATCH PATIENTS
CAR T-cell therapy, originally developed for treatment of blood cancers, can also make kidney transplant possible for patients who ordinarily would not be eligible, researchers have found, in a potential breakthrough for those with few options.
Some individuals with kidney failure are “sensitized,” which means their immune system has developed antibodies against foreign tissues – for example, from previous blood transfusions, pregnancies, or transplants – so their body is likely to reject most donor kidneys.
For highly sensitized patients, finding a suitable donor kidney can be difficult or impossible.
In cancer patients, CAR-T cell therapy involves removal of a patient’s immune cells, modification of those cells in the laboratory to teach them to hunt down and destroy cancer cells, and reinfusion into the patient.
Working with highly sensitized patients in need of new kidneys – two in a U.S. hospital and one in Germany – separate teams of researchers were able to modify the patients’ immune cells in the lab to reduce their antibody production and then reinfuse the modified immune cells to effectively “reset” their immune system.
All three patients experienced dramatic reductions in the harmful immune antibodies that typically attack donor kidneys.
As a result, all successfully received new kidneys, the two research teams reported on Wednesday in The New England Journal of Medicine.
“This is the first demonstration that CAR T cells can be used not only to treat cancer, but also to help patients who previously had no opportunity to receive a compatible donor kidney,” Dr. Ali Naji of the University of Pennsylvania, who led the care of the two U.S. patients, said in a statement.
“For patients who have spent years on the kidney transplant waiting list, this approach could be transformative.”
CAR-T CELL THERAPY MAY IMPROVE RHEUMATOLOGICAL DISEASES
CAR-T cell therapy is also showing promise for rheumatological disorders where other treatments have failed or stopped working, according to four pilot studies presented at the European Alliance of Associations for Rheumatology meeting in London.
In one study, six patients with rheumatoid arthritis that had not responded to other treatments received mivocabtagene autoleucel, an experimental CAR-T cell therapy being developed by Kyverna Therapeutics. All participants had decreases in disease activity and half of them achieved sustained remission.
At follow-up ranging from 24 to 36 weeks, five of the six patients remained off immunosuppressive therapy, Fredrik Albach of Charité Universitätsmedizin in Berlin reported at the meeting.
Separately, Yajing Zhang from Beijing GoBroad Boren Hospital, China reported on 11 patients with refractory systemic sclerosis, a severe autoimmune disease that causes hardening of tissues. After administering CD19/BCMA CAR-T cell therapy, skin thickness scores and lung tissue scarring improved significantly from baseline.
“By effectively targeting both skin fibrosis and lung progression, this immunological ‘reset’ strategy offers true curative potential, paving the way for (mid-stage) trials to redefine the future management of this severe disease,” Zhang said in a statement.
Yuichi Maeda of the Friedrich-Alexander-Universität Erlangen-Nürnberg and colleagues tested the experimental CAR-T cell therapy zorpocabtagene autoleucel from Miltenyi Biomedicine in individuals with severe systemic lupus erythematosus, systemic sclerosis, or an autoimmune muscle disease known as idiopathic inflammatory myopathy, in an effort to improve the diversity of healthy bacteria in patients’ intestines.
Overgrowth of unhealthy bacteria “decreased to levels comparable to those of healthy controls after the treatment,” the researchers said, and the immune activity contributing to patients’ symptoms was significantly decreased.
The authors concluded that CAR T-cell therapy reshapes gut microbiota in patients with autoimmune diseases, and these immunomicrobial shifts may support long-term disease remission.
Finally, Xiaobing Wang of Shanghai Changzheng Hospital and colleagues reported that use of CAR-T cell therapy in four patients with systemic lupus erythematosus or systemic sclerosis resulted in “deep, tissue-level remission.”
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(Reporting by Nancy Lapid; Editing by Bill Berkrot)
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