期刊
ONCOIMMUNOLOGY
卷 2, 期 6, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/onci.24612
关键词
GM-CSF; HSV; immunotherapy; JX594; reolysin; talimogene laherparepvec
资金
- Ligue Nationale contre le Cancer (equipe labellisee)
- Agence Nationale de la Recherche
- AXA Chair for Longevity Research
- Association pour la Recherche sur le Cancer
- Canceropole Ile-de-France
- Institut National du Cancer (INCa)
- Fondation Bettencourt-Schueller
- Fondation de France
- Fondation pour la Recherche Medicale
- European Commission (ArtForce)
- European Research Council
- LabEx Immuno-Oncology
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (Socrate)
- Cancer Research and Personalized Medicine (Carpem) consortium
- Paris Alliance of Cancer Research Institutes (Pacri)
Oncolytic virotherapy is emerging as a promising approach for the treatment of several neoplasms. The term oncolytic viruses is generally employed to indicate naturally occurring or genetically engineered attenuated viral particles that cause the demise of malignant cells while sparing their non-transformed counterparts. From a conceptual standpoint, oncolytic viruses differ from so-called oncotropic viruses in that only the former are able to kill cancer cells, even though both display a preferential tropism for malignant tissues. Of note, such a specificity can originate at several different steps of the viral cycle, including the entry of virions (transductional specificity) as well as their intracellular survival and replication (post-transcriptional and transcriptional specificity). During the past two decades, a large array of replication-competent and replication-incompetent oncolytic viruses has been developed and engineered to express gene products that would specifically promote the death of infected (cancer) cells. However, contrarily to long-standing beliefs, the antineoplastic activity of oncolytic viruses is not a mere consequence of the cytopathic effect, i.e., the lethal outcome of an intense, productive viral infection, but rather involves the elicitation of an antitumor immune response. In line with this notion, oncolytic viruses genetically modified to drive the local production of immunostimulatory cytokines exert more robust therapeutic effects than their non-engineered counterparts. Moreover, the efficacy of oncolytic virotherapy is significantly improved by some extent of initial immunosuppression (facilitating viral replication and spread) followed by the administration of immunostimulatory molecules (boosting antitumor immune responses). In this Trial Watch, we will discuss the results of recent clinical trials that have evaluated/are evaluating the safety and antineoplastic potential of oncolytic virotherapy.
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