"Father of CAR-T" Cell Opinion Article: CAR-T cell therapy has gone beyond cancer

Carl June, "CAR-T pioneer" and tenured professor at the Perelman School of Medicine at the University of Pennsylvania, was also named one of
the "2018 Global Top 100 Influential People" by Time magazine for this achievement.
In 2011, Carl June's team successfully cured Emily Whitehouse, a little girl with a recurrence of acute leukemia, with CAR-T therapy, and until now, Emily has survived cancer-free for ten years without signs of recurrence, which is a miracle
in the medical world 。 After achieving the first breakthrough success in CAR-T clinically, Professor Carl June and Penn University School of Medicine licensed this technology to pharmaceutical giant Novartis, and in 2017 achieved the approval of the world's first CAR-T new drug Kymriah, turning the most spectacular page
in the history of cell immunotherapy.

Engineered immune cells, known as CAR-T cells, have shown the world how personalized immunotherapy can play
in fighting blood cancers.
Now, researchers have reported very promising early results
for CAR-T therapy in a small group of patients with the autoimmune disease lupus.
Carl June, MD, a pioneer in CAR-T at the Pennsylvania Medical School, and Daniel Baker, a doctoral student in cell and molecular biology at the University of Pennsylvania's Perelman School of Medicine, discussed the advance
in a commentary published today in the journal Cell.

"We've always known that CAR-T therapies could have broad applications in principle, and it's very encouraging to see early evidence that this promise is materializing," June said
.

T cells are one of the
immune system's most powerful weapons.
They can bind and kill other cells they deem effective targets, including virus-infected cells
.
CAR-T cells are T cells that are redirected through genetic engineering and can effectively kill specific cell types
.

CAR-T therapies are created in each patient's own cells — cells are collected from the patient's blood, then engineered and multiplied in the lab, and then reinfused into the patient as a "living drug
.
" The first CAR-T therapy, Kymriah, was developed by June and his team at the Pennsylvania Medical School and was approved
by the Food and Drug Administration in 2017.
In the United States, there are currently six FDA-approved CAR-T cell therapies used to treat six different types of cancer
.
These therapies have revolutionized the treatment of certain B-cell leukemias, lymphomas and other blood cancers, allowing many patients who would otherwise have no hope of long-term remission to recover
.

Since the beginning of CAR-T research, experts have believed that T cells can be engineered to fight many diseases
beyond B-cell cancer.
Dozens of research teams around the world are working on these potential new applications, including teams at the University of Pennsylvania School of Medicine and the Biotechnology Branch, which are working to develop effective treatments
from personalized cell therapy structures developed at the University of Pennsylvania.
June and Baker's comments are a response to the success of these efforts in the first major clinical report: a paper
published in Nature Medicine by German researchers on the use of CAR-T therapy to treat the autoimmune disease lupus (systemic lupus erythematosus).

Lupus is an obvious choice for CAR-T therapy because it is also driven by B cells, so experimental CAR-T treatments targeting it can use existing anti-B-cell designs
, the researchers said.
B cells are cells that the immune system produces antibodies, and in lupus, B cells attack the patient's own organs and tissues
.

In the German study, five young adults did not benefit
from standard lupus treatment.
However, all went into remission and were able to stop taking their lupus medication within three months of a relatively small dose of CAR-T treatment, which essentially removed their existing B cells
.
(Cancer patients then need to be infused with purified human antibodies from healthy volunteers to maintain some immunity
.
) More notably, all patients remained in remission during a year-long follow-up period
.
Unlike cancer patients, lupus patients recover B cells, which are naturally replenished
by blood stem cells in the bone marrow.

In their comments, Baker and June note that although the results of the German study need to be confirmed by larger studies and longer-term follow-up, they are very promising — in fact, they believe that lupus may be a more likely target for CAR-T than B-cell carcinoma
.

"The number of disease-driven B cells in lupus erythematosus is much smaller, so effective CAR-T therapy for this autoimmune disease may require lower doses, which would greatly reduce the problem of
immune side effects.
"

Original:

CAR T therapy extends its reach to autoimmune diseases