TY - JOUR
T1 - Oncolytic herpes simplex virus immunovirotherapy in combination with immune checkpoint blockade to treat glioblastoma
AU - Saha, Dipongkor
AU - Martuza, Robert L.
AU - Rabkin, Samuel D.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Oncolytic viruses, such as oncolytic herpes simplex virus (oHSV), are a new class of cancer therapeutic, which selectively replicate and kill cancer cells, while inducing an inflammatory microenvironment, immunovirotherapy. Recently, an oHSV (talimogene laherparepvec) has been approved for the treatment of advanced melanoma. Glioblastoma (GBM) is an almost always lethal primary tumor in the brain that is highly immunosuppressive, and posited to contain GBM stem-like cells (GSCs). Immune checkpoint blockade has revolutionized therapy for some cancers, but not GBM. We have used a syngeneic GSC-derived orthotopic GBM model (005) to develop immunotherapeutic strategies. Curative therapy required oHSV expressing IL-12 in combination with two checkpoint inhibitors, anti-PD-1 and anti-CTLA-4. This response required CD4+ and CD8+ T cells, and macrophages in a complex interplay.
AB - Oncolytic viruses, such as oncolytic herpes simplex virus (oHSV), are a new class of cancer therapeutic, which selectively replicate and kill cancer cells, while inducing an inflammatory microenvironment, immunovirotherapy. Recently, an oHSV (talimogene laherparepvec) has been approved for the treatment of advanced melanoma. Glioblastoma (GBM) is an almost always lethal primary tumor in the brain that is highly immunosuppressive, and posited to contain GBM stem-like cells (GSCs). Immune checkpoint blockade has revolutionized therapy for some cancers, but not GBM. We have used a syngeneic GSC-derived orthotopic GBM model (005) to develop immunotherapeutic strategies. Curative therapy required oHSV expressing IL-12 in combination with two checkpoint inhibitors, anti-PD-1 and anti-CTLA-4. This response required CD4+ and CD8+ T cells, and macrophages in a complex interplay.
KW - cancer immunotherapy
KW - cancer stem cells
KW - checkpoint inhibitors
KW - glioma
KW - HSV
KW - immunovirotherapy
KW - macrophage polarization
KW - oncolytic virus
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85050151471&origin=inward
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85050151471&origin=inward
U2 - 10.2217/imt-2018-0009
DO - 10.2217/imt-2018-0009
M3 - Article
C2 - 30008259
SN - 1750-743X
VL - 10
SP - 779
EP - 786
JO - Immunotherapy
JF - Immunotherapy
IS - 9
ER -
