COVER STORY
38 THE WEEK · JULY 29, 2018
HEALTHDR PARAMESWARAN HARI,
chief of oncology at the Medical
College of Wisconsin, talked about
their phenomenal work:The promise of treating cancer with
activated T cells are huge. How
much is hype and how much can we
hope?
Many of us believe this is the begin-
ning of a huge wave of new thera-
pies.
How long would it take to transfer
the CAR-T research results from
the lab to the patients?
Two CAR-T products have been
approved. Generally from small tri-
als to FDA approval, it takes four to
six years.
Can you explain how the new ther-
apy works and what is novel about
the method of manufacture?
Our CAR-T cell is genetically engi-
neered or programmed to recognise
and attack cells bearing one or both
of two proteins, CD19 and CD20.
The commercial CAR-T cells so
far only target CD19. Our CAR-T
cell will hopefully work even when
CD19 is not there or is lost.
The method of manufacturing is
unique and novel. We make it lo-
cally at our cancer centre in a desk-
top machine and there is no trans-
portation of cells. The CliniMACS
Prodigy device collects the patient's
own T cells and augments them
with cancer-fi ghting genes, produc-
ing new cells ready to be infused
back into the bloodstream within
14 days. It saves a lot of time for the
patient.
Companies and universities are rac-
ing to develop these new therapies
that turn the patient's own immune
cells into cancer killers. How expen-
sive will the new treatment be?
The reasons for exorbitant prices
for any new cancer therapy is be-
cause commercial development isTHE CAR-T (chimeric antigen receptor T-cells) treat-
ment came into limelight with a five-year-old girl, Emily
Whitehead, who was diagnosed with acute lymphoblastic
leukemia. After two rounds of chemotherapy, Emily devel-
oped a bacterial infection that would eat away the flesh on
her legs. She barely managed to avoid amputation. But, she
had a relapse and was advised bone marrow transplanta-
tion. She went in for a third round of chemotherapy which
got her three weeks of life, but no cure. That was when the
University of Pennsylvania was going in for the human trials
of a new therapy called CAR-T therapy (anti-CD19 to be spe-
cific), which modified the patient's T cells genetically to kill
tumour cells. Emily's parents enrolled her. This was in 2011,
and by 2013 December, she was free of the disease. Now
Emily is a happy, healthy teenager.
Her survival injected new life into a line of treatment that
was very near failure. Carl June, who lost his wife to ovarian
cancer, developed the CAR-T at the Penn University. While
June was working hard, it was Barbara and Edward Netter
who helped June with the finances.They had lost their
daughter-in-law to cancer, too. This tragedy got them to
start the Alliance for Cancer Gene Therapy (ACGT), hoping
to develop alternative approaches. The one million dollars
contributed by ACGT was enough to carry forward the initial
studies. There were more downs to June's research than
ups, and he would have given up if not for Emily's recovery.
By August 2017, FDA approved the first CAR-T therapy, with
Novartis's tisagenlecleucel hitting the market for patients
up to 25 years of age. As much as 83 per cent of children
who received the treatment in phase II trial had complete
elimination of malignant cells in three months.
The first ever CAR T-cells were developed by the Israeli
immunologist Zelig Eshhar in 1993. It has since then under-
gone a lot of evolution. Now, as many as 40 pharma compa-
nies, some in collaboration with academic institutions, are
on a race to find CAR-T treatment for different types of can-
cer. Gilead has completed almost all formalities to acquire
Kite Pharma for $11.9 billion, whose CAR-T technology,
initially developed at the National Institutes of Health (NIH),
was found to be effective against a certain type of non-
Hodgkin’s lymphoma. The pharma companies believe that
CAR-T will soon be effective against solid tumours too.Brief history of
CAR-T therapy