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Immunotherapy “A new frontier” Candace S. Johnson, PhD
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Immunotherapy is the new focus in oncology
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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
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The Immune System
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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
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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
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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.
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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
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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
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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
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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
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Recent FDA approval for first engineered T cell
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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.