Harnessing immune calls to fight cancer A success story
thank you thank you so much for giving
me this opportunity today
to come here and talk to you all and
particularly thank you for allowing me
to talk about the success story
of how your immune cells can be
manipulated to
to help patients with cancer and how we
are saving lives
i can tell you i’m even more excited to
talk about this
not just as a cancer researcher or a
breast medical oncologist but i’m also
very very very grateful that i can talk
about this because i’m someone
who’s living with cancer because of this
immunotherapy
and one thing i can tell you
unfortunately unfortunately this is not
a short story
i gotta talk to you in 15 minutes but
this is an epic
story that spans over 150 years and i’m
going to try to talk to you this
about this in 15 minutes so spare with
me and i have to tell them next slide so
next slide please
okay so what is this connection between
the immune system
and and cancer right so we’re always
talking about this connection
now look around you look around you and
think about the number of
carcinogens you’re either breathing in
or you’re swallowing every day or you’re
tasting or it’s touching your skin or
you’re feeling it
now look at that those are the list of
known carcinogens next slide please
there are two big slides of just talking
to you about
the known carcinogens that’s there okay
and if i have to put out the list of
potential other carcinogens i’ll be here
another hour
okay so next slide please
so there are so many carcinogens around
us but now let’s look at the number of
cancer patients
so in this annually in this whole world
the incidence of new cancers is about 17
million
okay and how many people are living on
this earth right now
7.8 billion people are walking around
this earth
being exposed to these carcinogens
wherever they are living in whatever
form
and we have only 17 million cases how is
that possible what is going on
okay next slide please and
what is happening when you are either
breathing or touching or inhaling these
carcinogens right that’s what we need to
understand
what these carcinogens do is that they
break your dna
they cause dna damage and dna is your
genetic code
dna is the code that tells your k normal
cells to do their job
and then if these kind of breaks the
misinterpretation of your genetic
material
if it is not corrected then over time
these are going to become rogue cells
and instead of
going through a normal cell cycle of
multiplying and then dying
they’re going to continue to multiply
and there we go
can cells keep multiplying they grow and
they’re going to become a tumor
and they’re going to become cancerous
all right so that’s the problem with
these carcinogens
next slide please what does your immune
cell do
immune cells are able to recognize these
damaged cells and they’re able to
eliminate that
let’s think about that a little bit more
i could give you an example
think of your immune cells as somebody
who proofreads
okay as an editor so there is all these
dna breaks and look at that there is
a bunch of jumbled words because your
dna genome has to be in a sequence
and if the sequence goes away then
you’re going to get damaged cells you’re
not going to get effective cells
so think of your immune cells are you as
proofreaders and they cannot correct
these typos
and then you have a whole system called
dna repair
system in your body and it goes and
tries to repair these cells
okay but what can happen though
these damaged cells our potential cancer
cells are very smart
and what they can do is they can confuse
your immune cells
and then as you can see that next next
slide please
they can make it so complex they can
make it so complex and camouflage
themselves now the
immune cells are a bit confused they’re
not able to unjumble these words
now even then you’re able to live in an
equilibrium some bad cells but
a good cells and you’re still able to
live well so you’re kind of living in
this environment where you’re still
doing okay
but if this continues to overcome your
immune
cells then by natural selections these
bad cells will continue to grow
and there you have next slide please
there you go you have an
escape but immune escape and you have
the cancer
okay that’s how your immune cells are
working every day
next slide please so think of your
immune system as really your first line
of defense
think of two words immune surveillance
kind of watching out for those bad cells
immune editing getting rid of those bad
cells
and in case in case that they camouflage
and
overwhelm the system there’s going to be
immune escape
and when that those cells escape that’s
when you’re going to have growth and
and development of cancer okay next
slide please
so we understand how your immune system
is fighting and
keeping cancer away but now you that
have
cancer already developed how can you
harness and use
your own immune cells to fight those
cancer cells that is the question right
this is not a question in the last 10
years i just want to share with you
there
that paper there is from late 1800s and
early 1900s
there was who was considered the father
of immunology dr bill coley
and he actually did this then he took
infected material from other patients
which had germs and immune cells
and and injected them into patients with
bone cancer and actually showed
reduction of the cancer all the way back
here talking nearly 150 years ago
but and the the way he has put together
it’s taken us of course this long to
make it
uh more available and we’ll talk about
that in a minute
so these immune cells are what are these
immune cells in your body
that’s your next question it’s your
white cells it’s your lymphocytes and we
have this lymphoid organs
all of these help us to fight this
cancer and just broadly think about how
best can you fight you either make
these bad cells more visible to your
immune cells
or you improve your immunity so that it
can find those bad cells and clear them
right that’s a simple principle
next slide please this is just to show
you
the top on that you can’t probably see
it all that is like in
mid-1800s and it’s all the way down
all of these discoveries over so many
people
internationally talk about our previous
speaker just talked about
connection working together that’s
what’s happened
internationally all of us working
together and next slide please
and that put together all of these
people these are the number of nobel
laureates
of course i would never say these are
the people that only people who
contributed right these are just
the tip of the iceberg so many
scientists so many people
so many people who worked in the lab the
undergrads the post graduates
so many people who toiled at night and
if you look at them
diverse group of people from all over
the world working in this country in
other country
countries that’s where we got but i want
to highlight two people there that you
see the names dr allison dr honjo
they got the nobel prize for physiology
and medicine just recently
because they found the negative
regulators of
immune cells and we’re going to talk
about that this is the ads that you
consistently see on tv about how
immunotherapy is changing lives
of various patients next slide please
so this is again broadly what can we do
what is your cancer cell doing it’s
hiding from your immune cell and how is
it doing it’s
cloaking itself just like you would
think like in a tsa
a terrorist gets through the checkpoint
and that’s what it’s doing it’s trying
to get away from your immune cell so we
need to get
your immune cells close to the cancer
cells we then
we need to break those bonds so that
your immune cells can spew out those
juices that can go
and kill these cancer cells so principle
of immune therapy is that what but it’s
not that easy to just do that within the
milieu of a host of a human being
next slide please i want to take a
little moment
on this because there are different
types of immune therapy and you would
hear these words
broadly they fall into five categories
the first one is vaccines
and what do we do with vaccines we
actually passively give you the immunity
we
give you the immunity to the patients
and they
then able to go fight whether it’s an
infection or cancer cells
okay that is one type and then there is
cytokines
what we do is take those juices you saw
those juices those immune spell
cells spill on the cancer cells now we
can actually inject those cytokines and
that’s an approved treatment
and what is the other option is called
adoptive cell therapy where you take
the t cells from the patient change it
in the lab and make it more
you know fighter cells and then give it
back to the patient
and then the fourth one which is what
we’re going to spend more time on today
are the checkpoint inhibitors these are
the ones that are making huge waves
saving lives
that is to close down the negative
regulators of
immune cells and then lastly is the
virus therapies again you have heard of
this oncolytic viruses
what do we do so the viruses are
interesting
you know uh uh creatures so to speak so
when they get into the host when they
get into the human
they incorporate themselves into the rna
and they can multiply within the cell
so now imagine you give a virus
attenuated virus that it’s not
going to immediately cause you an
infection you give it into the tumor it
incorporates itself into the
tumor and then starts to multiply now
your cancer
your immune cells can recognize them you
know as a virus particle they have to
fight it
they go and try to kill the virus in the
process your tumor cells are killed
so these are different types of immune
therapy but we’re going to hone in on
those checkpoint inhibitors
next slide please okay so on this side
you see three molecules pdl1ctl4
what are those things those are all
present in our body
all the time they are negative
regulators of your immune system
why do we need that we need to be
careful right so your body sees a
bacteria
it’s a simple bacteria you need a little
bit of immune response to kill it that’s
it
you don’t want your body to mount an
extraordinary response
you don’t want to take an ak-47 for a
simple family
squabble well i hope you never take an
ak-47 that’s a different matter
but so you want to have an immune
response that is commissioned to the
injury
so your body has these natural
mechanisms to kind of
modulate your immune therapy well what
does this cancer cell do
smart guys right and we need to get rid
of them they try to use
these negative regulators to protect
themselves so now we have to use in a
cancer patient
stuff that can inhibit the negative
regulator so that your t cells can
actually go fight them
so here you see you’ve seen that that’s
what is showing how they
break that bond and these are the
inhibitors seven
drugs that are already approved and
being treated uh with base for patients
right now next slide please
i want you to hone in on this i
obviously don’t have time to give you
all the data which i
could we could talk for hours i’ve taken
one example of
response to a a checkpoint inhibitor or
this immunotherapy in patients with
bladder and kidney cancer
hone in on those green lines these
patients tumor went down but more
importantly honed on how long it stayed
down
so what these immunotherapies are doing
those patients who respond respond
amazingly well and respond for a long
time
so we’re trying to make this cancer into
a chronic disease
but don’t forget next slide please watch
those
tumors or patients who did not respond
so we have work to do
so those tumors are going up we’ll come
to that okay
so these are all the cancers you can
read them there are 14 cancers many of
them are
very very serious cancers lung cancer
metastatic melanoma liver cancer kidney
cancer breast cancer
for all of which right now immunotherapy
is approved in various format or other
seven drugs approved for 14 different
cancers making
waves and saving lives and let’s see
what kind of impact it’s having
next slide please so if you look at it
between 1991 to 2017
we were reducing cancer related
mortality by 1.1
just between 2016 to 2017
the mortality has gone down all cause
cancer mortality
by two point double that now to you two
point two percent might
seem low but what are we talking about
we’re talking about millions of patients
right when you think globally that’s the
kind of impact we can have
and think about metastatic melanoma one
of the worst disease once it becomes
metastatic particularly after it goes to
the brain and
other organs we are saving more lives
in those patients we are have increased
or decreased their mortality by
seven percent between every year every
year by 7.7
from 2013 to 17 the one year survival
rate of patients with metastatic
melanoma went from 42
to 55 within a few years we’re saving so
many lives with
lung cancer which is a very aggressive
cancer and also i want to take a moment
about those patients with brain cancer
brain cancer that spread to the brain
which is one of the worst situations
these immunotherapy are actually
impacting those cells in the brain so
really an amazing story next slide
please
so are we done is it over we’re done
we’ve cured cancer
absolutely not the door is open the case
is not done the case is not over
i shared that with you because so many
patients even within melanoma even with
lung cancer where it works are not
responding as well as it’s
i only talk to you about 14 cancers
there are so many cancers for which we
need such treatments
that will work and work for a longer
time who are these patients where it
works how do we figure that out
and also about toxicity and i want a
moment to talk about that
so you might think is there no downside
because you do get to keep your hair
it’s not chemo and there’s definitely
one good thing there
but it can as your body is raising the
immune cells to fight the cancer cells
it can also fight your own cells so
someone’s thyroid might stop working
that pituitary might stop working they
might have severe diarrhea
so there are autoimmune side effects
that we need to address so there are
things that we need to do
and that is very critical for us next
slide please
so how are we doing that that’s exactly
what we’re doing
at the pelotonia institute of oncology
at the james and we’re doing this by
creating
a novel breakthrough treatment for
cancer a holistic
approach to cancer by bringing in
science basic scientists oncologists
endocrinologists rheumatologists
and really trying to bring people
together next slide please
and we are going to be impacting
prevention treatment and a survivorship
and how can we do this i’m going to go
back to the theme of this topic
we need to connect whom have we got to
connect we’ve got to connect to the
stakeholders
who are the stakeholders you are all the
stakeholders we will not have the
pelotonia institute of technology uh
sorry institute of even
oncology without you all because it was
the pelotonia fund
you all volunteering there you are all
supporting there these donors and the
community
connecting with them connecting with the
patients right but the patient should be
willing to go on trials
willing to give their tissue willing to
give their blood for and without them
will be nowhere
we need to connect with all the funding
agencies we need to connect with the
pharma who have to make the drug
we need to connect with government
officials nci needs to support us
and then bring in all the experts and
things so because if we connect
if we connect well we can create a
cancer free world
and that is our goal today and every day
and we will get there
last slide please and i just want to say
thank you
thank you to all that was truly in a
nutshell
and i am really grateful my life has
been a privilege to be
able to take care of patients and do
research but i am also
gifted i’m it’s a gift every day because
it is this immunotherapy that’s keeping
me alive being able to talk to you here
today thank you
and have a good day good night thank you