Overcoming immunosuppression to enhance a p53MVA vaccine.
A Phase I trial of a p53-targeting modified vaccinia Ankara (p53MVA) vaccine in patients afflicted with refractory gastrointestinal cancers demonstrated enhanced T-cell recognition of p53 following vaccination. However, this effect was transient suggesting that p53MVA requires combination with immunomodulatory agents to deliver clinical benefit. Here, we outline our rationale for combining p53MVA with immunomodulatory chemotherapy in a forthcoming trial.
Division of Translational Vaccine Research; Beckman Research Institute.
Nicola
N
Hardwick
Department of Medical Oncology; City of Hope National Medical Center ; Duarte, CA USA.
Vincent
V
Chung
Department of Medical Oncology; City of Hope National Medical Center ; Duarte, CA USA.
Mihaela
M
Cristea
Cedars-Sinai Medical Center ; Los Angeles, CA USA.
Joshua DI
JD
Ellenhorn
Division of Translational Vaccine Research; Beckman Research Institute.
Don J
DJ
Diamond
DC, dendritic cells; MDSC, myeloid-derived suppressor cells; MVA; MVA, modified vaccinia Ankara; PD-1, programmed death receptor1; PDL-1, programmed death receptor 1 ligand; Tregs, regulatory T cells; clinical trial; gemcitabine; immunotherapy; ovarian cancer; p53