VACCINES TO END CANCER MARY L. (NORA) DISIS ASSOCIATE DEAN, - - PowerPoint PPT Presentation
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
ATHENA DISTINGUISHED PROFESSOR OF BREAST CANCER RESEARCH AMERICAN CANCER SOCIETY CLINICAL RESEARCH PROFESSOR PROFESSOR OF MEDICINE DIRECTOR, UW MEDICINE CANCER VACCINE INSTITUTE
http://drjockers.com
http://www.basis-medical.com
Bindea et al, Curr Opin Immunol, 2010
Cold: Majority Non-responders? Hot: Minority Responders?
http://www.basis-medical.com
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 on ths afte r E nro llm ent
P e rce n t su rv iva l
1 2 2 4 3 6 4 8 6 0 7 2 8 4 9 6 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 fin e d n = 3 8
M on ths afte r E nro llm ent
P e rce n t re la p s e -fre e s u rv iv a l
1 2 2 4 3 6 4 8 6 0 7 2 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
infused, followed by further vaccination
Stanton et al, JITC, 2016
111In labeling
B a s e lin e 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 s te rn u m R s a c ru m 1 0 2 0 3 0 4 0 5 0 % in c re a s e M e ta s ta tic S ite s
Evidence of T-cell trafficking
Velasco-Velazquez et al, Int J Biochem Cell Biol, 2012
A g e (d a y s ) P erce n t T um o r F ree 5 0 1 0 0 1 5 0 2 0 0 2 5 5 0 7 5 1 0 0
p=0.0004 Control Stemvac
p=0.0004
Trial Design Polyvalent vaccine: CDH3, YB1, SOX2, CD105, MDM2 40 transgenic mice Free of palpable disease, 6weeks Vaccinated 1/month Significant immunity generated
Disis et al, CCR Focus, 2013
Provide Type I immunity Increase Type I immunity Release Type I immunity Propagate immune response
VACCINES IMMUNE CHECKPOINT INHIBITION
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