Three Minute Thesis Finals: First Place Winner | Johns Hopkins Medicine

Inside each of us right now,
cancer-like cells are growing. Luckily, this isn’t
as bad as it sounds, because most of us have healthy,
active immune systems. When one of our cells
becomes damaged or undergoes mutation, our immune
cells seek it out, killing or neutralizing it before it
grows into clinical disease. We all have cancer-like cells,
but only some of us have cancer. Unfortunately, this isn’t
a fool proof system. Tumor cells are clever. Over time,
they can change their appearance, adopting disguises that allow
them to evade immune control. Those of us who work in
cancer immunotherapy, therefore, have two goals. First, to identify the mechanisms
by which tumors escape the immune system, and second, to develop
treatments that unmask cancer, reversing these negative effects. When I mention immune cells,
I’m referring to a specific type called CD8 T cells, which are very
well-equipped to target and kill tumors but generally do
not target our healthy cells. If they do,
they’re prevented from killing. Molecules on the T cell surface seek
out the signs of a healthy cell, and if they find them, like a light
switch, the T cell is turned off. Tumor cells exploit this, disguising
themselves as healthy cells and switching off any killer
T cells that come near. One of these switch-like
molecules is called LAG-3. As the T Cell nears the tumor,
something flips the LAG-3 switch making this
cancer-killing cell inactive. Through binding studies, I have identified the culprit as
a small protein called galectin-3. The tumor cells and their neighbors
are able to release this tiny protein into the surrounding area. And when large amounts of it are
present, they bind to each other and to the switch-like molecule, LAG-3. This type of binding is
called cross-linking, and it is what allows the T cell to
receive that deactivation signal. When we inject cancer cells into
mice that cannot make galectin-3, their T cells works so well that most of those
mice never grow a tumor. So we understand the mechanism. Now, we need to learn
how to reverse it. My studies now turn to testing
potential treatments, substances that block galactin-3 that keep it
from flipping the LAG-3 switch, and that allow T cells to
remain potent tumor killers. We believe that this approach could
lead me to the day when I will be able to say to all of you,
we all have cancer-like cells, but none of us have cancer. Thank you. [APPLAUSE]

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