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Developing Oncolytic Viruses for the Treatment of Cervical Cancer.

ABSTRACT: Cervical cancer represents one of the most important malignancies among women worldwide. Current therapeutic approaches for cervical cancer are reported not only to be inadequate for metastatic cervical cancer, but are also considered as cytotoxic for several patients leading to serious side effects, which can have negative implications on the quality of life of women. Therefore, there is an urgent need for the development of innovative and effective treatment options. Oncolytic viruses can eventually become effective biological agents, since they preferentially infect and kill cancer cells, while leaving the normal tissue unaffected. Moreover, they are also able to leverage the host immune system response to limit tumor growth. This review aims to systematically describe and discuss the different types of oncolytic viruses generated for targeting cervical cancer cells, as well as the outcome of the combination of virotherapy with conventional therapies. Although many preclinical studies have evaluated the therapeutic efficacy of oncolytic viruses in cervical cancer, the number of clinical trials so far is limited, while their oncolytic properties are currently being tested in clinical trials for the treatment of other malignancies.

SUBMITTER: Kalafati E

PROVIDER: S-EPMC10377776 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Developing Oncolytic Viruses for the Treatment of Cervical Cancer.

Kalafati Eleni E Drakopoulou Ekati E Anagnou Nicholas P NP Pappa Kalliopi I KI

Cells 20230713 14

Cervical cancer represents one of the most important malignancies among women worldwide. Current therapeutic approaches for cervical cancer are reported not only to be inadequate for metastatic cervical cancer, but are also considered as cytotoxic for several patients leading to serious side effects, which can have negative implications on the quality of life of women. Therefore, there is an urgent need for the development of innovative and effective treatment options. Oncolytic viruses can even ...[more]

PMID: 37508503

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Project description:Identification of the immune suppressive mechanisms active within the tumor microenvironment led to development of immunotherapeutic strategies aiming to reverse the immunosuppression and to enhance the function of tumor-infiltrating lymphocytes. Of those, cancer therapy with antibodies targeting the immune costimulatory and coinhibitory receptors has demonstrated significant promise in the recent years, with multiple antibodies entering clinical testing. The responses to these agents, however, have not been universal and have not been observed in all cancer types, calling for identification of appropriate predictive biomarkers and development of combinatorial strategies. Pre-existing immune infiltration in tumors has been demonstrated to have a strong association with response to immunotherapies, with the type I interferon (IFN) pathway emerging as a key player in tumor innate immune recognition and activation of adaptive immunity. These findings provide a rationale for evaluation of strategies targeting the type I IFN pathway as a means to enhance tumor immune recognition and infiltration, which could potentially make them susceptible to therapeutics targeting the cosignaling receptors. To this end in particular, oncolytic viruses (OVs) have been demonstrated to enhance tumor recognition by the immune system through multiple mechanisms, which include upregulation of major histocompatibility complex and costimulatory molecules on cancer cells, immunogenic cell death and antigen release, and activation of the type I IFN pathway. Evidence is now emerging that combination therapies using OVs and agents targeting immune cosignaling receptors such as 4-1BB, PD-1, and CTLA-4 may work in concert to enhance antitumor immunity and therapeutic efficacy. Our evolving understanding of the interplay between OVs and the immune system demonstrates that the virus-induced antitumor immune responses can be harnessed to drive the efficacy of the agents targeting cosignaling receptors and provides a strong rationale for integration of such therapies in clinic.

Project description:Oncolytic viruses are emerging as a potential new way of treating cancers. They are selectively replication-competent viruses that propagate only in actively dividing tumor cells but not in normal cells and, as a result, destroy the tumor cells by consequence of lytic infection. At least six different oncolytic herpes simplex viruses (oHSVs) have undergone clinical trials worldwide to date, and they have demonstrated an excellent safety profile and intimations of efficacy. The first pivotal Phase III trial with an oHSV, talimogene laherparepvec (T-Vec [OncoVex(GM-CSF)]), is almost complete, with extremely positive early results reported. Intuitively, therapeutically beneficial interactions between oHSV and chemotherapeutic and targeted therapeutic drugs would be limited as the virus requires actively dividing cells for maximum replication efficiency and most anticancer agents are cytotoxic or cytostatic. However, combinations of such agents display a range of responses, with antagonistic, additive, or, perhaps most surprisingly, synergistic enhancement of antitumor activity. When synergistic interactions in cancer cell killing are observed, chemotherapy dose reductions that achieve the same overall efficacy may be possible, resulting in a valuable reduction of adverse side effects. Therefore, the combination of an oHSV with "standard-of-care" drugs makes a logical and reasonable approach to improved therapy, and the addition of a targeted oncolytic therapy with "standard-of-care" drugs merits further investigation, both preclinically and in the clinic. Numerous publications report such studies of oncolytic HSV in combination with other drugs, and we review their findings here. Viral interactions with cellular hosts are complex and frequently involve intracellular signaling networks, thus creating diverse opportunities for synergistic or additive combinations with many anticancer drugs. We discuss potential mechanisms that may lead to synergistic interactions.

Dataset Information

Developing Oncolytic Viruses for the Treatment of Cervical Cancer.

Publications

Developing Oncolytic Viruses for the Treatment of Cervical Cancer.

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