bladder cancers treated with CTLA- 4 antibodies, readings from
the Gatling gun showed that T cells possessing a molecule called
ICOS were “o; the charts.” Sharma’s reaction was elation mixed
with confusion. T cells with ICOS on them had previously been
found only in the tiny sacs in the lymph nodes known as follicles, and they were believed to suppress immune responses, not
enhance them. Allison decided to engineer mice whose tumors
triggered ICOS. In their tumors, CTLA- 4 was four times as e;ective. ICOS, it turns out, was part of cascade that made T cells
attack tumor cells more e;ectively.
“I can’t believe we missed this,” Allison remembers telling
Sharma. “This is amazing.” He’d been scooped by his collaborator and felt blown away. They’d been spending more and time
together, talking on the phone and working on science. Now he
blurted out: “I love you!” Sharma recalls plowing forward with
the conversation as if nothing had been said. But he had said it.
The pair were married in a small ceremony in 2014.
With the help of the Boston venture capital firm Third Rock
Ventures, they also started a company called Jounce Therapeutics that is developing a drug to increase ICOS levels. Human
tests got under way last year, and although it’s too early to know
how the drug is working, the idea has already been remunerative. Jounce went public in January, raising $117 million. Now
Sharma drives a Tesla with a vanity plate that reads “ICOS.” On
Allison’s Porsche, the plate says “CTLA4.”
“I CAN’T BELIEVE
WE MISSED THIS.
THIS IS AMAZING ...
I LOVE YOU!”
At MD Anderson,
where James Allison
has his laboratory,
why some people
don’t benefit from