Personalized Cancer Therapy PowerPoint Presentation

Personalized Cancer Therapy PowerPoint Presentation

2018-11-21 7K 7 0 0

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Immunotherapy. George Weiner, MD. Director, Holden Comprehensive Cancer Center. Professor, Department of Internal Medicine. George Weiner, MD. Disclosure. Consultant and Research Funding. Checkmate Pharmaceuticals. ID: 731536

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Presentations text content in Personalized Cancer Therapy

Slide1

Personalized Cancer TherapyImmunotherapy

George Weiner, MDDirector, Holden Comprehensive Cancer CenterProfessor, Department of Internal Medicine

Slide2

George Weiner, MDDisclosure

Consultant and Research Funding

Checkmate Pharmaceuticals

Advisory BoardSandoz

Slide3

Medieval Saxon man with a large tumor of the left femur

We Have Been at War Against Cancer Throughout Human History

President Nixon declares a “War on Cancer

” in 1971

Vice President Biden

Cancer

Moonshot

Slide4

The Fight Against Cancer

Takes place in every cancer patient

Between the cancer and the immune system

Slide5

Immune systemDistinguishes “self” from “non self”

Eliminate

Infection

Attack Own Cells

Autoimmunity

Rejection of

Invaders

Slide6

Immune systemOver-active immune response

Infection

Autoimmunity

Slide7

Immune systemUnder-active immune response

Autoimmunity

Infection

Slide8

Goal of cancer immunotherapyBend the immune system curve

Eliminate

Cancer

AvoidAutoimmunity

Slide9

Immunity

Inside

Cells

Immunity

Outside

Cells

Antibodies

T Cells

Slide10

Ideal Cancer Immunotherapy TargetOvercome fact that cancer is “self”

Need to break tolerance (help immune system see the target as “non-self”)Expression

Selectively on malignant cells (or non-vital tissues)On all malignant cells in a tumorFunction

Necessary for cell survival or malignant phenotype

Slide11

The “War on Cancer” at the individual level…

Primary Combatants

:

Malignant cellsHost immune system

The host immune system is

an active

enemy faced by a developing cancer

All

“successful” cancers

must

avoid immune destruction

Weapons

Target on

surface of cell –

Antibody-based treatment

Target inside

cancer cell – T

cell-based treatment

Slide12

Major approaches to cancer immunotherapyAntibodiesAdminister

anti-cancer antibodies to patientsAdminister antibodies that alter the immune response to the cancerT-cellsCancer vaccines

Change tumor environment so the immune system recognizes and eliminates the cancer (in situ immunization)Take

out T cells, change them so they are specific for the cancer, and give them back to the patient

Slide13

Building better monoclonal antibody-based therapeutics

George J. Weiner

Nature Reviews Cancer June 2015

Slide14

Steps Necessary for Antibody-Drug Conjugate to be Effective

ADC

Receptor-Mediated Endocytosis

Lysosome

Target

Antigen

Slide15

Most

cancers have many mutations

Mutated proteins represent potential

targets

for immune recognition and destruction

Lawrence, Nature 499:214 2013

Slide16

Topalian

, Weiner,

Pardoll

JCO 2012Turning on and off T cells – Its complicated

Slide17

Immune Checkpoints Regulate Strength and Type of Anti-Tumor Immune Response

Pardoll

, Nat Rev Cancer 2012

Slide18

Remove

cancer’s “invisibility

cloak”

Cancer cells express molecules that prevent immune system from recognizing and eliminating cancer

We now can block these molecules with

mAb

allowing the immune system to recognize and eliminate the cancer

x

Slide19

Slide20

Clinical Activity

of the

Concurrent Regimen of

Nivolumab

and

Ipilimumab

in Advanced Melanoma

Wolchok

JD et al. N

Engl

J Med 2013;369:122-

133

Sznol M et al,

Proc

ASCO LBA9003 2014

Follow

Up

April 2015

(

Proc

AACR 2015)

Overall response rate ~ 6

0

%

Complete response rate ~

25%

Median survival

>

40

mos

(expected survival ~ 7

mos

)

Few relapses in responders

Combination blockade of PDL1-PD1 and B7-CTLA4 interactions aiming to overcome “defensive” checkpoint inhibitors

Slide21

Marcela V.

Maus

et al. Blood 2014;123:2625-2635

CAR T-cells are genetically engineered

T

cells

Antibody fragment is used to retarget T cells towards cancer

Chimeric

Antigen Receptor

T-cells

(CAR T cells)

Slide22

Production and treatment with CAR

T

cells

https://junotherapeutics.com/our-science/scientific-platform/

Slide23

Combination cancer immunotherapy

Cancer Immunotherapy and Breaking Immune Tolerance:New Approaches to an Old Challenge

Makkouk and WeinerCancer Research

2015Multiple mechanisms that limit autoimmunity need to be overcome in cancer immunotherapy

Slide24

Change the tumor micro-environment

The

Qb

and G10 components self-assemble into highly-ordered icosahedral VLPs (~30 nm)

Make a virus-like particle that is non-infectious but the stimulates the immune system

Inject it directly into the cancer

The immune system is stimulated to identify the cancer as foreign

T cells travel throughout the body to fight the cancer

24

Slide25

Pretherapy

Week 4

Week 6

Injected lesion

Clinical response of anti-PD1 refractory melanoma patient treated with anti-PD1 plus in situ CMP-001

Photos courtesy of M. Milhem

Slide26

Pillars of Cancer Therapy

Surgery

Radiation

Immuno

Chemo

Targeted

Slide27


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