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