TY - JOUR
T1 - Oncolytic Adenoviruses
T2 - The Cold War against Cancer Finally Turns Hot
AU - Oronsky, Bryan
AU - Gastman, Brian
AU - Conley, Anthony P.
AU - Reid, Christopher
AU - Caroen, Scott
AU - Reid, Tony
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/10
Y1 - 2022/10
N2 - Oncolytic viruses, colloquially referred to as “living drugs”, amplify themselves and the therapeutic transgenes that they carry to stimulate an immune response both locally and systemically. Remarkable exceptions aside, such as the recent 14-patient trial with the PD-1 inhibitor, dostarlimab, in mismatch repair (MMR) deficient rectal cancer, where the complete response rate was 100%, checkpoint inhibitors are not cure-alls, which suggests the need for a combination partner like oncolytic viruses to prime and augment their activity. This review focuses on adenoviruses, the most clinically investigated of all the oncolytic viruses. It covers specific design features of clinical adenoviral candidates and highlights their potential both alone and in combination with checkpoint inhibitors in clinical trials to turn immunologically “cold” and unresponsive tumors into “hotter” and more responsive ones through a domino effect. Finally, a “mix-and-match” combination of therapies based on the paradigm of the cancer-immunity cycle is proposed to augment the immune responses of oncolytic adenoviruses.
AB - Oncolytic viruses, colloquially referred to as “living drugs”, amplify themselves and the therapeutic transgenes that they carry to stimulate an immune response both locally and systemically. Remarkable exceptions aside, such as the recent 14-patient trial with the PD-1 inhibitor, dostarlimab, in mismatch repair (MMR) deficient rectal cancer, where the complete response rate was 100%, checkpoint inhibitors are not cure-alls, which suggests the need for a combination partner like oncolytic viruses to prime and augment their activity. This review focuses on adenoviruses, the most clinically investigated of all the oncolytic viruses. It covers specific design features of clinical adenoviral candidates and highlights their potential both alone and in combination with checkpoint inhibitors in clinical trials to turn immunologically “cold” and unresponsive tumors into “hotter” and more responsive ones through a domino effect. Finally, a “mix-and-match” combination of therapies based on the paradigm of the cancer-immunity cycle is proposed to augment the immune responses of oncolytic adenoviruses.
KW - cancer immunity cycle
KW - checkpoint inhibitors
KW - immunosuppression
KW - oncolytic adenoviruses
KW - priming
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U2 - 10.3390/cancers14194701
DO - 10.3390/cancers14194701
M3 - Review article
C2 - 36230621
AN - SCOPUS:85139971026
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 19
M1 - 4701
ER -