Carl June, the father of CAR-T, commented: Beyond cancer, CAR-T successfully treats lupus erythematosus

CAR-T cell therapy is to isolate T cells from the patient's body and genetically engineer them to kill tumor cells
.
At present, CAR-T cell therapy has shown strong effects in hematologic malignancies, and the FDA has approved several CAR-T cell therapies for marketing
.

On November 23, 2022, Professor Carl June, the "father of CAR-T" and the University of Pennsylvania, published a review article in the journal Cell entitled: CAR-T therapy extends its reach to autoimmune diseases [1], commenting on the very promising effect
of CAR-T cell therapy in the treatment of patients with the autoimmune disease systemic lupus erythematosus.

Professor Carl June said that in principle we have always known that CAR-T therapy can be widely used, and the early results of CAR-T treatment for systemic lupus erythematosus are very encouraging
.

Professor Carl June

CAR-T therapy is genetically engineered by each patient's own T cells, collected from the patient's blood, engineered and expanded in the laboratory, and then reinfused back into the patient as a "live-cell drug
.
" The world's first CAR-T therapy, Kymriah, was developed by Carl June and his team at the Pennsylvania Medical School and was approved by the FDA in 2017
.

There are currently a total of six FDA-approved CAR-T cell therapies for the treatment of cancer
.
These CAR-T therapies have revolutionized the treatment of certain B-cell leukemias, lymphoma and other blood cancers, allowing many cancer patients who otherwise had no hope of long-term remission to recover
.

From the beginning, scientists believed that CAT-T cells could be engineered and engineered to fight many other diseases
besides B-cell cancer.
Dozens of research teams around the world are working on these potential new applications
.

In September 2022, Professor Georg Schett's team from the University of Erlangen-Nuremberg (FAU) in Germany published a research paper in Nature Medicine entitled: Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus [2].

The study reported improvement in all five patients with refractory systemic lupus erythematosus after CAR-T cell therapy, no recurrence at up to 17 months follow-up, and no drug-free remission
.

In this clinical trial, five patients (4 women and 1 male) with refractory systemic lupus erythematosus aged 22 years were enrolled between February 14, 2021 and February 2, 2022
.
All patients had histologically confirmed glomerulonephritis and heart, lung, and joint involvement
.
Although young, all patients have been previously treated with several immunosuppressants, including glucocorticoids, hydroxychloroquine, mycophenolate mofetil, belimab, and others
.

The research team treated the five patients
with modified anti-CD19 CAR-T cells.
These cells are designed to clear antibody-producing B cells
by targeting the CD19 protein produced on their surface.

After 3 months of CAR-T cell administration, all 5 patients with lupus erythematosus experienced sustained improvement in signs and symptoms, including disappearance of nephritis, resolution of arthritis, fatigue, heart valve fibrosis, and lung involvement
.
Of note, after treatment, patients could discontinue all immunomodulatory and immunosuppressive drugs, including glucocorticoids and hydroxychloroquine, and all 5 patients achieved drug-free remission
.

At long-term follow-up, although B cells reappeared in patients, no relapse was observed in patients up to 17 months, while all patients were still not treated with any systemic lupus erythematosus treatment drugs
.
In addition, all patients experienced only mild side effects associated with CAR-T cell therapy, such as fever
.
No infection
occurred at short-term follow-up and during the stage of B-cell hypoplasia.

Professor Andreas Mackensen (left), Professor Georg Schett (right), and in the center is Thu-Thao V, the world's first patient with systemic lupus erythematosus treated with CAR-T cells.

Carl June noted in the review that although this CAR-T treatment for lupus erythematosus results still need to be confirmed by larger studies and longer-term follow-up, this result is very promising
.
In fact, this study suggests that lupus erythematosus may be a more likely target for CAR-T cell therapy than
B-cell tumors.

In addition, the number of disease-driven B cells in lupus erythematosus is much smaller, so CAR-T treatment of autoimmune diseases such as lupus may only require lower doses, which will greatly reduce the immune
side effects of CAR-T cell therapy.

Original source:

Daniel J.
Baker， Carl H.
June.
CAR T therapy extends its reach to autoimmune diseases.
Cell， 2022.