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TRANSCRIPT
VACCINES TO END CANCER
MARY L. (NORA) DISIS
ASSOCIATE DEAN, TRANSLATIONAL HEALTH
SCIENCE, UW SCHOOL OF MEDICINE
ATHENA DISTINGUISHED PROFESSOR OF BREAST CANCER RESEARCH
AMERICAN CANCER SOCIETY CLINICAL RESEARCH PROFESSOR
PROFESSOR OF MEDICINE
DIRECTOR, UW MEDICINE CANCER VACCINE INSTITUTE
THE POWER OF THE IMMUNE SYSTEM
http://drjockers.com
OUR TWO ARMS OF IMMUNITY
√
√
HARNESSING THE IMMUNE RESPONSE
The end of many common infectious diseases
THE CANCER SPECIFIC IMMUNE RESPONSE
Educate
Activate
Disseminate
http://www.basis-medical.com
Cancer
T-cells
Innate cell
EFFECTIVE IMMUNITY AGAINST CANCER
Bindea et al, Curr Opin Immunol, 2010
Immune score
TYPE I TYPE II
The type of immunity
needed to kill cancer
There are “good” guys and there are “bad” guys
Regulate immunity
How cancer escapes from the immune system
Immunogenic cancer proteins are “self”
Immune checkpoint inhibitor antibodies
Taking the break off the immune system
Immune therapy now an essential part of
cancer therapy… for some cancers
“Hot” vs. “Cold” tumors
Cold: Majority
Non-responders?Hot: Minority
Responders?
Can cold tumors become hot?
CANCER VACCINES
Educate
Activate
Disseminate
http://www.basis-medical.com
Cancer
T-cells
Innate cell
What are the steps to a clinically
effective cancer vaccine?
How cancer escapes from the immune system
Cancer must look dangerous to
the immune system
Vaccines to create the right response
Identify the most immunogenic portions
of the cancer protein
“Bar code” of vaccine hot spots
Therapeutic vaccines Prevention vaccines
Target cancer drivers
CLINICAL STRATEGY FOR CANCER VACCINES
Vaccine priming
for T-cell therapy
Prevention of
disease recurrence
Prevention of
development of
cancer
Trial Design
Phase II
38 patients
First dx Stage IV HER2+
breast cancer
Start vaccines within 6
months of maintenance
trastuzumab
CR or stable bone only
disease
LVEF within normal limits
6 vaccines, id, I month apart
M o n th s a fte r E n ro llm e n t
Pe
rce
nt
su
rviv
al
0 1 2 2 4 3 6 4 8 6 0 7 2 8 4 9 6
0
2 0
4 0
6 0
8 0
1 0 0
M e d ia n S u rv iv a l = U n d e f in e d
n = 3 8
M o n th s a fte r E n ro llm e n t
Pe
rce
nt
rela
ps
e-f
ree
su
rviv
al
0 1 2 2 4 3 6 4 8 6 0 7 2
0
2 0
4 0
6 0
8 0
1 0 0
M e d ia n S u rv iv a l =
n = 3 8
32.8
Overall survival
Progression
free survival
HER-2/neu a breast cancer driver
Vaccine primed T-cells for adoptive T-cell therapy
• HER2+, extensive bone mets
• HER2 vaccine primed T-cells expanded,
infused, followed by further vaccination
• Disease stabilization for 18 months
Stanton et al, JITC, 2016
111In labeling
Base
line
Liv
er
c ontr
ol
L a
x illary
node
R h
um
eru
s
L h
um
eru
s
s tern
um
R s
ac ru
m
0
1 0
2 0
3 0
4 0
5 0
% i
nc
rea
se
M e ta s ta tic S ite s
Evidence of T-cell trafficking
Treatment of advanced metastatic breast cancer
Velasco-Velazquez et al, Int J Biochem Cell Biol, 2012
Targeting breast cancer stem cells for
cancer prevention
A g e (d a y s )
Pe
rce
nt
Tu
mo
r F
ree
0 5 0 1 0 0 1 5 0 2 0 0
0
2 5
5 0
7 5
1 0 0
p=0.0004
Control
Stemvac
Phase I trial: Ongoing
p=0.0004
Prevention of the development of cancer
Trial Design
Polyvalent vaccine: CDH3,
YB1, SOX2, CD105,
MDM2
40 transgenic mice
Free of palpable disease,
6weeks
Vaccinated 1/month
Significant immunity
generated
VACCINES TO END CANCER
Disis et al, CCR Focus, 2013Provide Type I immunity
Increase Type I immunity
Release Type I immunity Propagate immune response
VACCINES
IMMUNE CHECKPOINT
INHIBITION
Vaccinate
prior to
cancer
Translational Laboratory
Denise Cecil
Ben Curtis
Yushe Dang
Katie Hitchcock-Bernhardt
Hee Jin Lee
John Liao
Laura Riolobos
Sasha Stanton
Clinical Trials
Jennifer Childs
Andrew Coveler
Will Gwinn
Doreen Higgins
Hania Shakalia
Immune Monitoring Laboratory
Angela Kask
Yi Yang
Mouse Modeling Core
Lauren Corulli
Paul Cowen
Ekram Gad
Erin Rodmaker
Administration and Support
Tess Banyon
Chad Boyer
Jennifer Sheldon
