our immune system is amazing not only
that it has the ability to protect our
bodies against harmful viruses and
bacterias it also protects our body
against cancer our immune system has the
natural ability to detect and destroy
cancer cells sometimes we want to help
our immune system and build memory and
for that as kids and growing up we get
vaccines these vaccines program our
immune system to detect and to recognize
a pathogen a pathogen is the cause of
the disease we are working on cancer
vaccines and this is important because
cancer is a very sophisticated disease
cancer cells develop the ability to
evade the immune system surveillance
they can hide from it they can inhibit
it or sometimes there’s just too many
cancer cells and they overwhelm the
immune system our cancer vaccine in
preclinical models in mice was able to
stimulate those immune cells that were
inhibited to give them the power to
destroy the tumor to seek new tumors
destroy them and remember them sounds
pretty amazing let me tell you how we
did it but first let’s talk about
vaccines when we get vaccines we usually
the pathogen is given when it’s
inactivated or weakened it is perceived
by our immune system as foreign and
start a chain of signaling events that
leads to the activation of b-cells and
t-cells both of them are immune cells
activated b-cells produce a protein it’s
called an antibody this antibody can
bind to specific structure on the
pathogen and to signal to other immune
cells to come and destroy this pathogen
t-cells can themselves kill cells that
were infected with the pathogen but the
most important part
about the vaccine is the generation of
memory cells and these memory cells if
they encounter the same pathogen in the
future they can respond to it but now
the response will be stronger and faster
cancer vaccines use the same
immunological mechanism but they’re
slightly different the pathogen vaccine
is given before the onset of the disease
our therapeutic cancer vaccine is given
after the tumour is detected we are
injecting directly into the tumor immune
modulating molecules and these molecules
stimulate t-cells within the tumor to
destroy the tumor to expand to go out in
the body and look for other cancer cells
destroy them and just like with the
pathogen vaccine in cancer vaccine the
most important thing is the generation
of memory cells but then when the memory
is not against the pathogen it’s against
the cancer this is a really nice idea
but now we had to find those molecules
that could perform it and for that we
needed a really good screen and for the
screen we choice we chose mice mice
immune system is similar to ours
relatively in our moms models the mice
were inoculated with two tumors we
injected directly into the tumor the
molecule that we tested and we could
have we could assess the effect of this
molecule on this tumor we treated but we
are a door head also the other tumor
that was not treated and we could look
at the whole body affect the systemic
effect of the rest of the molecule we
had a control group of mice that were
not treated at all and their tumor kept
on growing and growing some of the
molecules that we tested had exactly the
same effect they had no effect
whatsoever on tumor growth then we
tested a molecule that is called CPG
it’s a short sequence of DNA
it doesn’t have a signature like
mammalian DNA it looks more like a viral
or a bacterial DNA and when it was
injected directly into the tumor it was
recognized and for it as foreign and
started a local immune response that was
sufficient to redress this treated tumor
but it didn’t have much of an effect on
the non treated tumor so it wasn’t good
enough we kept on searching then we
tested a different molecule now it was a
protein an antibody and this antibody
target is expressed on t-cells when the
antibody binds the target on the t-cells
it activates them the name of the target
is ox40
the name of the antibody is anti ox for
T when we injected anti Oxford e
directly into one of the tumors because
also only a slight delay in the tumor
growth but when we combined CPG and anti
oxidant a same syringe and injected it
into one of the tumors not only that the
treated tumor completely regressed now
also the non treated tumor went away the
mice were completely cured we waited
three months which is a long time in the
lifespan of a mouse and then we rejected
those mice with the same tumor cells and
none of the mice developed tumors they
were all resistant to this cancer they
all had memory of this tumor we tested
the combination of CPG and antioxidants
models of melanoma breast cancer colon
cancer and lymphoma and in all of them
it was successful cancer vaccines are
part of a treatment that is called
immunotherapy immunotherapies our
treatment that meant to enhance your
immune response to fight cancer when
you’re enhancing your immune response
you can also stimulate an immune
response
again against the healthy tissue and it
could result in autoimmunity by
injecting directly into the tumor we
could reduce the dose to 1/100 of the
dose that you would use for systemic
administration hoping that this was will
result in less autoimmunity but it
raised a really important question is
there something specific about the
immune response that we are enhancing
here to the tumor or is it something
general and to answer this question we
had a different tumor models and now the
mice were inoculated with three tumors
two of them were identical here in
orange shown for example lymphoma and
another one which was different here in
green shown may be colon cancer we
treated only one of the identical tumors
thinking that if there is something
specific about our immune response we
will see the effect only on the other
lymphoma tumor but not on the colon
cancer and that’s exactly what happened
we wanted to confirm our findings so we
repeated the experiment but now we had
two colon cancers and one live form a
tumor we treated one of the colon tumors
and only the other colon tumor went away
not the lymphoma so we could stimulate
an immune response that was specific to
the tumor that we treated human tumors
not like these mice tumors tend to be
more heterogeneous meaning that the
cells are slightly different from one
another so now we wanted to know can we
stimulate an immune response against
cells that are slightly different from
one another and for that we now had a
different model where we had one tumor
that consisted of a mixture of the
lymphoma cells and colon cancers and we
had one separate lymphoma tumor and one
separate colon tumor we treated a mixed
tumor thinking that if we can simulate a
that he gives against different cells
will see the response afterwards also on
the lymphoma and the colon cancer and
that’s exactly what happened
all of these tumors completely regressed
all of these mice experiments were done
so far on transplantable tumor models
but now we wanted to learn more about a
more natural way of tumor development
and we for that we chose a strain of
mice that spontaneously develop breast
cancer they develop breast cancer in
older ten mammary glands in a sequential
manner so the first one arises and then
throughout the body
this is a very aggressive model and like
human breast cancer it also sends
metastases to the lungs we treated only
one of these tumors the first one we
could detect and we monitor the tumor
growth throughout the body this is the
only time in my presentation where I’m
going to show you a picture of an actual
mouse but I think it’s important to see
all the red arrows indicate tumor cells
this is a non treated Mouse but that’s
what happened when we give only three
injections of CPG and antioxidant tumor
we detect not only the tumor load is
significantly reduced the number of the
lung Mets is also reduced and the mice
lived longer we think that these results
are amazing but they were all done in
mice a couple of weeks ago the first
clinical trial was open to evaluate the
combination of CPG Ananta Oxford E in
patients with non-hodgkins lymphoma
we believe that promising results will
lead to more trials testing in different
types of cancers as for the preclinical
work our work here is not done I’m going
back to the lab to now work on a more
aggressive tumors to see what we can do
to tumors that do not
on to any therapy what we can add to CPG
an anti Oxford e to make them now work
in respond to therapy and we’re not
alone here
researchers all over the world are
working on immunotherapy looking for the
next molecule looking for the next
target looking for the next combination
that will make our immune system even
more amazing thank you [Applause]
that it has the ability to protect our
bodies against harmful viruses and
bacterias it also protects our body
against cancer our immune system has the
natural ability to detect and destroy
cancer cells sometimes we want to help
our immune system and build memory and
for that as kids and growing up we get
vaccines these vaccines program our
immune system to detect and to recognize
a pathogen a pathogen is the cause of
the disease we are working on cancer
vaccines and this is important because
cancer is a very sophisticated disease
cancer cells develop the ability to
evade the immune system surveillance
they can hide from it they can inhibit
it or sometimes there’s just too many
cancer cells and they overwhelm the
immune system our cancer vaccine in
preclinical models in mice was able to
stimulate those immune cells that were
inhibited to give them the power to
destroy the tumor to seek new tumors
destroy them and remember them sounds
pretty amazing let me tell you how we
did it but first let’s talk about
vaccines when we get vaccines we usually
the pathogen is given when it’s
inactivated or weakened it is perceived
by our immune system as foreign and
start a chain of signaling events that
leads to the activation of b-cells and
t-cells both of them are immune cells
activated b-cells produce a protein it’s
called an antibody this antibody can
bind to specific structure on the
pathogen and to signal to other immune
cells to come and destroy this pathogen
t-cells can themselves kill cells that
were infected with the pathogen but the
most important part
about the vaccine is the generation of
memory cells and these memory cells if
they encounter the same pathogen in the
future they can respond to it but now
the response will be stronger and faster
cancer vaccines use the same
immunological mechanism but they’re
slightly different the pathogen vaccine
is given before the onset of the disease
our therapeutic cancer vaccine is given
after the tumour is detected we are
injecting directly into the tumor immune
modulating molecules and these molecules
stimulate t-cells within the tumor to
destroy the tumor to expand to go out in
the body and look for other cancer cells
destroy them and just like with the
pathogen vaccine in cancer vaccine the
most important thing is the generation
of memory cells but then when the memory
is not against the pathogen it’s against
the cancer this is a really nice idea
but now we had to find those molecules
that could perform it and for that we
needed a really good screen and for the
screen we choice we chose mice mice
immune system is similar to ours
relatively in our moms models the mice
were inoculated with two tumors we
injected directly into the tumor the
molecule that we tested and we could
have we could assess the effect of this
molecule on this tumor we treated but we
are a door head also the other tumor
that was not treated and we could look
at the whole body affect the systemic
effect of the rest of the molecule we
had a control group of mice that were
not treated at all and their tumor kept
on growing and growing some of the
molecules that we tested had exactly the
same effect they had no effect
whatsoever on tumor growth then we
tested a molecule that is called CPG
it’s a short sequence of DNA
it doesn’t have a signature like
mammalian DNA it looks more like a viral
or a bacterial DNA and when it was
injected directly into the tumor it was
recognized and for it as foreign and
started a local immune response that was
sufficient to redress this treated tumor
but it didn’t have much of an effect on
the non treated tumor so it wasn’t good
enough we kept on searching then we
tested a different molecule now it was a
protein an antibody and this antibody
target is expressed on t-cells when the
antibody binds the target on the t-cells
it activates them the name of the target
is ox40
the name of the antibody is anti ox for
T when we injected anti Oxford e
directly into one of the tumors because
also only a slight delay in the tumor
growth but when we combined CPG and anti
oxidant a same syringe and injected it
into one of the tumors not only that the
treated tumor completely regressed now
also the non treated tumor went away the
mice were completely cured we waited
three months which is a long time in the
lifespan of a mouse and then we rejected
those mice with the same tumor cells and
none of the mice developed tumors they
were all resistant to this cancer they
all had memory of this tumor we tested
the combination of CPG and antioxidants
models of melanoma breast cancer colon
cancer and lymphoma and in all of them
it was successful cancer vaccines are
part of a treatment that is called
immunotherapy immunotherapies our
treatment that meant to enhance your
immune response to fight cancer when
you’re enhancing your immune response
you can also stimulate an immune
response
again against the healthy tissue and it
could result in autoimmunity by
injecting directly into the tumor we
could reduce the dose to 1/100 of the
dose that you would use for systemic
administration hoping that this was will
result in less autoimmunity but it
raised a really important question is
there something specific about the
immune response that we are enhancing
here to the tumor or is it something
general and to answer this question we
had a different tumor models and now the
mice were inoculated with three tumors
two of them were identical here in
orange shown for example lymphoma and
another one which was different here in
green shown may be colon cancer we
treated only one of the identical tumors
thinking that if there is something
specific about our immune response we
will see the effect only on the other
lymphoma tumor but not on the colon
cancer and that’s exactly what happened
we wanted to confirm our findings so we
repeated the experiment but now we had
two colon cancers and one live form a
tumor we treated one of the colon tumors
and only the other colon tumor went away
not the lymphoma so we could stimulate
an immune response that was specific to
the tumor that we treated human tumors
not like these mice tumors tend to be
more heterogeneous meaning that the
cells are slightly different from one
another so now we wanted to know can we
stimulate an immune response against
cells that are slightly different from
one another and for that we now had a
different model where we had one tumor
that consisted of a mixture of the
lymphoma cells and colon cancers and we
had one separate lymphoma tumor and one
separate colon tumor we treated a mixed
tumor thinking that if we can simulate a
that he gives against different cells
will see the response afterwards also on
the lymphoma and the colon cancer and
that’s exactly what happened
all of these tumors completely regressed
all of these mice experiments were done
so far on transplantable tumor models
but now we wanted to learn more about a
more natural way of tumor development
and we for that we chose a strain of
mice that spontaneously develop breast
cancer they develop breast cancer in
older ten mammary glands in a sequential
manner so the first one arises and then
throughout the body
this is a very aggressive model and like
human breast cancer it also sends
metastases to the lungs we treated only
one of these tumors the first one we
could detect and we monitor the tumor
growth throughout the body this is the
only time in my presentation where I’m
going to show you a picture of an actual
mouse but I think it’s important to see
all the red arrows indicate tumor cells
this is a non treated Mouse but that’s
what happened when we give only three
injections of CPG and antioxidant tumor
we detect not only the tumor load is
significantly reduced the number of the
lung Mets is also reduced and the mice
lived longer we think that these results
are amazing but they were all done in
mice a couple of weeks ago the first
clinical trial was open to evaluate the
combination of CPG Ananta Oxford E in
patients with non-hodgkins lymphoma
we believe that promising results will
lead to more trials testing in different
types of cancers as for the preclinical
work our work here is not done I’m going
back to the lab to now work on a more
aggressive tumors to see what we can do
to tumors that do not
on to any therapy what we can add to CPG
an anti Oxford e to make them now work
in respond to therapy and we’re not
alone here
researchers all over the world are
working on immunotherapy looking for the
next molecule looking for the next
target looking for the next combination
that will make our immune system even
more amazing thank you [Applause]
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