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0:00
My name is Ryan Sullivan.
I am at the Mass
General Cancer Center
in Boston and the
Harvard Medical School.
Today I'm here to talk
about where we are
with mRNA neoantigen
vaccinations.
0:14
I think it's important to
start with the basics.
When we think about
cancer vaccination,
targeting antigen
selection is paramount.
There are two general
types of antigens.
There are
tumor-associated antigens
and tumor-specific antigens.
Tumor-associated antigens can
be overexpressed proteins,
typically differentiation
antigens in various tissues but
then are overexpressed in
tumors and then cancer
testis antigens.
These have variable
tumor specificity and
variable central tolerance as
is depicted in this cartoon.
But these are also shared across
many populations of
cancer patients.
Whereas tumor-specific
antigens can be viral
in origin and oncoviral antigens
are commonly targeted
in vaccines.
They can be shared neoantigens
and they can be
private neoantigens.
The tumor specificity of
tumor-specific
antigens are optimal.
There should be no
central tolerance and
oncoviral and shared
neoantigens are
shared across populations and
private neoantigens are not.
1:19
In addition to
antigen selection,
the next thing that we have
to think about is
adjuvant selection.
Vaccine adjuvants tend to be
innate immune activators
for microbial detection.
These tend to rely on
pattern recognition
receptors such as
TLRs and RLR agonists,
and these dominate in
the vaccine world both in
cancer vaccination and
other vaccination strategies
and they're designed
to generate cell
mediated immunity.
In the cartoon, there are a number
of different types of adjuvants
that are used in some
of the cytokines and
other attributions that
these adjuvants have.
