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 Activate T-cells Innate cell Cancer Educate Disseminate http://www.basis-medical.com
EFFECTIVE IMMUNITY AGAINST CANCER Immune score Bindea et al, Curr Opin Immunol, 2010
There are “good” guys and there are “bad” guys TYPE II TYPE I The type of immunity Regulate immunity needed to kill cancer
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 Hot: Minority Non-responders? Responders? Can cold tumors become hot?
CANCER VACCINES Activate T-cells Innate cell Cancer Educate Disseminate http://www.basis-medical.com 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
Target cancer drivers Therapeutic vaccines Prevention vaccines
CLINICAL STRATEGY FOR CANCER VACCINES Prevention of development of cancer Prevention of disease recurrence Vaccine priming for T-cell therapy
HER-2/neu a breast cancer driver Overall survival 1 0 0 P e rce n t su rv iva l 8 0 6 0 Trial Design 4 0 M e d ia n S u rv iv a l = U n d e fin e d Phase II n = 3 8 2 0 38 patients 0 First dx Stage IV HER2+ 0 1 2 2 4 3 6 4 8 6 0 7 2 8 4 9 6 breast cancer M on ths afte r E nro llm ent Start vaccines within 6 months of maintenance Progression 1 0 0 P e rce n t re la p s e -fre e s u rv iv a l trastuzumab free survival CR or stable bone only 8 0 disease 6 0 LVEF within normal limits 4 0 6 vaccines, id, I month apart 32.8 M e d ia n S u rv iv a l = n = 3 8 2 0 0 0 1 2 2 4 3 6 4 8 6 0 7 2 M on ths afte r E nro llm ent
Vaccine primed T-cells for adoptive T-cell therapy
Treatment of advanced metastatic breast cancer 5 0 Evidence of T-cell trafficking 4 0 111 In labeling % in c re a s e 3 0 2 0 1 0 0 L iv e r c o n tro l L a x illa ry n o d e R h u m e ru s L h u m e ru s B a s e lin e s te rn u m R s a c ru m M e ta s ta tic S ite s • 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
Targeting breast cancer stem cells for cancer prevention Velasco-Velazquez et al, Int J Biochem Cell Biol, 2012
Prevention of the development of cancer Trial Design 1 0 0 Polyvalent vaccine: CDH3, Stemvac YB1, SOX2, CD105, 7 5 MDM2 P erce n t T um o r F ree p=0.0004 40 transgenic mice 5 0 Control Free of palpable disease, 6weeks 2 5 Vaccinated 1/month p=0.0004 Significant immunity 0 generated 0 5 0 1 0 0 1 5 0 2 0 0 A g e (d a y s ) Phase I trial: Ongoing
VACCINES TO END CANCER Vaccinate prior to cancer Disis et al, CCR Focus, 2013 Provide Type I immunity VACCINES Increase Type I immunity IMMUNE CHECKPOINT Propagate immune response Release Type I immunity INHIBITION
Translational Laboratory Immune Monitoring Laboratory Denise Cecil Angela Kask Ben Curtis Yi Yang Yushe Dang Katie Hitchcock-Bernhardt Mouse Modeling Core Hee Jin Lee Lauren Corulli John Liao Paul Cowen Laura Riolobos Ekram Gad Sasha Stanton Erin Rodmaker Clinical Trials Administration and Support Jennifer Childs Tess Banyon Andrew Coveler Chad Boyer Will Gwinn Jennifer Sheldon Doreen Higgins Hania Shakalia
QUESTIONS? Nora Disis (206) 616-1823 ndisis@uw.edu
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