TY - JOUR
T1 - Oncolytic Virotherapy
T2 - A Contest between Apples and Oranges
AU - Russell, Stephen J.
AU - Peng, Kah Whye
N1 - Funding Information:
We acknowledge funding support from NIH/NCI for the Mayo Clinic?Myeloma SPORE (P50CA186781 to S.J.R. and R01CA175795 to K.-W.P.), the Mayo Clinic Comprehensive Cancer Center (P30CA015083), the Al and Mary Agnes McQuinn Foundation, and the David F. and Margaret T. Grohne Family Foundation.
Publisher Copyright:
© 2017 The American Society of Gene and Cell Therapy
PY - 2017/5/3
Y1 - 2017/5/3
N2 - Viruses can be engineered or adapted for selective propagation in neoplastic tissues and further modified for therapeutic transgene expression to enhance their antitumor potency and druggability. Oncolytic viruses (OVs) can be administered locally or intravenously and spread to a variable degree at sites of tumor growth. OV-infected tumor cells die in situ, releasing viral and tumor antigens that are phagocytosed by macrophages, transported to regional lymph nodes, and presented to antigen-reactive T cells, which proliferate before dispersing to kill uninfected tumor cells at distant sites. Several OVs are showing clinical promise, and one of them, talimogene laherparepvec (T-VEC), was recently granted marketing approval for intratumoral therapy of nonresectable metastatic melanoma. T-VEC also appears to substantially enhance clinical responsiveness to checkpoint inhibitor antibody therapy. Here, we examine the T-VEC paradigm and review some of the approaches currently being pursued to develop the next generation of OVs for both local and systemic administration, as well as for use in combination with other immunomodulatory agents.
AB - Viruses can be engineered or adapted for selective propagation in neoplastic tissues and further modified for therapeutic transgene expression to enhance their antitumor potency and druggability. Oncolytic viruses (OVs) can be administered locally or intravenously and spread to a variable degree at sites of tumor growth. OV-infected tumor cells die in situ, releasing viral and tumor antigens that are phagocytosed by macrophages, transported to regional lymph nodes, and presented to antigen-reactive T cells, which proliferate before dispersing to kill uninfected tumor cells at distant sites. Several OVs are showing clinical promise, and one of them, talimogene laherparepvec (T-VEC), was recently granted marketing approval for intratumoral therapy of nonresectable metastatic melanoma. T-VEC also appears to substantially enhance clinical responsiveness to checkpoint inhibitor antibody therapy. Here, we examine the T-VEC paradigm and review some of the approaches currently being pursued to develop the next generation of OVs for both local and systemic administration, as well as for use in combination with other immunomodulatory agents.
KW - T-VEC
KW - competitive landscape
KW - oncolytic virotherapy
KW - viro-immuno-oncology
UR - http://www.scopus.com/inward/record.url?scp=85017113587&partnerID=8YFLogxK
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U2 - 10.1016/j.ymthe.2017.03.026
DO - 10.1016/j.ymthe.2017.03.026
M3 - Review article
C2 - 28392162
AN - SCOPUS:85017113587
VL - 25
SP - 1107
EP - 1116
JO - Molecular Therapy
JF - Molecular Therapy
SN - 1525-0016
IS - 5
ER -