Hollings Annual Report 2023 FINAL - Flipbook - Page 12
Lymphodepleting chemo
Lymphodepleting chemotherapy kills off existing T-cells to
create a blank slate for CAR-T cells to treat certain blood
cancers, and research has shown that CAR-T cell therapy
is more effective after lymphodepleting chemotherapy.
However, the lymphodepleting chemotherapy can
contribute to some strong and scary side effects.
But Richard O’Neil, Ph.D., and graduate student Megan
Tennant (below), along with colleagues Christina
New, M.D., and Leonardo Ferreira, Ph.D., believe that
lymphodepleting chemotherapy isn’t necessary.
In a paper published in Molecular Therapy, they showed
that encoding the CAR-T-cells with instructions to create a
hyperactive form of protein STAT5 prompted the CAR-T
cells to engraft, or take root and begin multiplying, without
requiring lymphodepletion. In their experiments, the
engraftment process was cell autonomous, meaning it didn’t
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depend on the surrounding environment but happened
solely because of the instructions from within the cells.
“We present a lot of evidence in the paper to support that
notion that it’s a completely cell autonomous process, and
that it’s fundamentally driven by activation of STAT5,”
O’Neil said. “And so by transiently activating STAT5 during
that phase of adoptive transfer, the initial engraftment
phase, you’re tricking the cells into essentially thinking
they’re going into a lymphodepleted environment.”
HIV and cancer
Cancer is now the leading cause of death among
people with HIV, and prostate cancer is among the most
diagnosed cancers for this group, said epidemiologist
Ashish Deshmukh, Ph.D., co-leader of the Cancer Control
Research Program at MUSC Hollings Cancer Center. Yet
it’s not clear how HIV may affect the typical progression
Hollings 2023 Annual Report
