Immunotherapy “A new frontier” Candace S. Johnson, PhD

Immunotherapy is the new focus in oncology

Tipping point for cancer immunotherapy

• Major advances in the last 10 years – Your immune system protects you against cancer – Success with vaccination against HPV (Gardasil) – Knowledge of the immune system has increased

The Immune System

0 20 40 60 80 100 120 140Overall Survival (Months)

0.0

0.2

0.4

0.6

0.8

1.0

Cum

ulat

ive

Surv

ival

Intraepithelial CD8+ TILlowest tertileall others

Log Rank test P=0.009

Median survival: 55 vs. 26 months

Roswell Park Study: Immune responses in ovarian cancer = improved survival

Sato et al, PNAS, 2005, 102:18538

Immune cell (T cell)

Tumor cell

Immunotherapy – “living drug” not chemicals, a targeted answer to cancer:

http://www.theanswertocancer.org/

boosts your immune system to help eliminate cancer cells

enhances immune response by providing additional components

Cancer Immunotherapy

• Major advances recently – Several FDA approvals for a class of

immunotherapies – “immune checkpoint blockers”.

– Now approved for melanoma, lung, bladder, liver, kidney: and the list continues to grow.

Immunotherapy at RPCI: Leading the way

monoclonal antibodies

http://www.theanswertocancer.org/

oncolytic virus

checkpoint blockade adoptive T cell transfer

cancer vaccine cytokine/immunomodulator

• Not all immunotherapies are created equal • Which is the best immunotherapy for me? • Advanced next generation

Benefits of cancer immunotherapy

http://www.theanswertocancer.org/

Power to target cancer in a specific way Ability to work on many types of cancer even those that do not respond to chemo or radiation Potential for reduced side effects commonly associated with chemotherapy e.g. nausea, vomiting, hair loss Possibility for long-term remissions

Selection of trials conducted at Roswell Park: No cancer type is left behind

ovarian cancer

I 243813 LUD2014-011

I 276015

melanoma

I 243813 LUD2014-011

PH 227012

prostate cancer

I 243813 LUD2014-011

PH 283216

breast cancer

I 243813 LUD2014-011

PH 253914

colon cancer

I 243813 LUD2014-011

I 274515

lung cancer

I 243813 LUD2014-011

PH 269015

leukemia lymphoma

PH 236713

I 248613 I 277115

I 215912 I 250113 I 191511 I 191511 I 191511 I 227712

PH 281816

I 258514 I 230612 I 283616

I 258514 I 258514 I 223912

I 258514 I 258514 I 258514 PH 251514 I 210611

PH 268215

checkpoint blockade

LUD2015-001 LUD2015-001 PH 280416 oncolytic

virus

adoptive transfer

cancer vaccines

I 288216

Next generation immunotherapies at Roswell Park: Generating T cells for adoptive transfer therapy

TCR = T cell receptor CAR = chimeric antigen receptor

recognize and destroy tumor cells

TCR CAR

receptor transfer

Recent FDA approval for first engineered T cell

Our expectations of clinical outcomes of immunotherapy

100%

0%

% of treated patients alive

traditional therapies

immunotherapies

immunotherapies in combination

Time Traditional therapies: Lives extended, but responses often not durable. Disease progresses or recurs. Few lives ultimately saved.

Immunotherapies: Patients with sufficient anti-cancer immunity achieve durable disease control. Many lives are saved.