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institution to do this work. They invested in GMP facilities to
grow T cells." (GMP: good manufacturing practices, operating
at FDA approved standards)
Dr. June's initial experiments were with mice. By early
2009, the mice data was very promising. His research had been
funded by grants from the NIH and Leukemia and Lymphoma
Society. "We were ready to do human trials but we couldn't get
the funding. We had applied (for grants) several times. This was
the same time as the Wall Street collapse and there wasn't a lot of
philanthropic money. I had to fire a lot of people and I almost
closed the lab to all but basic science. But then in 2010, I received
a personal grant of $1 million from Edward and Barbara Netter
to continue to study gene therapy after their daughter-in-law,
Kimberly Lawrence Netter, passed away from breast cancer.
That provided the funding to start our first human trial. Our
first three patients all had positive results but again, we ran out
of money. The trial was for 14 patients and we couldn't get any
more grants. So, we decided to publish the initial results as a
case report and see what happens."
The amazing results by Dr. June and his research team explain
what happened next. The first three patients did very well indeed.
Two of the three patients treated in 2011 went into complete
remission and remain cancer free in 2018. They had chronic
lymphocytic leukemia and huge tumor burdens. All had failed
salvage chemotherapy. One of the patients had already paid for
his funeral. He received CAR T-cell therapy in August 2010.
An estimated five pounds of tumor were destroyed causing one
of the treatment side effects, cytokine release syndrome. After
surviving the side effects of this massive tumor kill, the doctors
looked for his cancer and could not find it. Believing they must
have made an error, they ran more studies but still couldn't find
it. The paper was submitted. In August 2011, it was published
in the New England Journal of Medicine. "Afterwards, we received
thousands of emails. Mike Milken calls and gives $1 million
to extend this research into prostate cancer. In August 2012,
Novartis gives $20 million for a translational cell facility, and in
2013, we published the results on the first child to receive CAR
T-cell therapy, Emily.
"During the first trial with a child, Emily Whitehead, we almost
lost her. She had a large tumor burden. The T cells attacking her
cancer caused severe cytokine release syndrome. She was in the
intensive care unit and dying."
The doctors found high levels of IL-6 in her blood. High levels
of IL-6 also had been found in the blood of the adult patients
receiving CAR T-cell therapy. Dr. June had just learned of a
new drug approved for rheumatoid arthritis whose mechanism
of action blocks IL-6. Emily was given this newly approved
anti-IL-6 drug, Tocilizumab. "She immediately improved." Emily
not only made a rapid recovery but she remains disease free to
this day. Dr. June is quite sure if she had not survived, pediatric
trials would have stopped, and we would not have this therapy

up coming
LECTURES AND EVENTS
may 6:

Psychoanalysis in a Troubled
World: Celebrating Three Recent
Books by Dr. Salman Akhtar

may 17: Public Health Grand Rounds:
Obesity and Its Prevention in
Philadelphia
may 29: Ludwig van Beethoven: Innovation
with Attitude!
with speaker Robert Greenberg

for more, visit: collegeofphysicians.org

available today. Tocilizumab is now the standard of care for treating
cytokine release syndrome and part of the FDA package insert for
this CAR T-cell therapy, tisagenlecleucel (KymriahTM), for treating
cytokine release syndrome.
I asked Carl a few more questions:
Has your life been different than you imagined? "You just can't
plan everything perfectly. Life is a lot of luck and timing. Yogi Berra
once said, 'If you come to a fork in the road, take it.' You have to
take the fork in the road."
What are the most important lessons that you have learned?
"Persistence. Having a long term attention span, because 90 percent
of the time you get a dud. Only every once in a while will you hit
the home run." Finally, how would you like to be remembered?
"Someone who tried to do something, had a great team to work
with, and a great network of friends."
So what is next? Solid tumors such as pancreatic cancer which
are much more effective at evading our immune system. Being able
to figure out how the immune system can successfully treat these
solid tumors would be a huge step toward the cure. Clearly these
next steps will be difficult. However, with Carl's current success
against the odds, my bets are with him.
Congratulations Carl! We wish you much future success! *

Spring 2018 : Philadelphia Medicine

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https://philamedsoc.org/ http://www.collegeofphysicians.org

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