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Oncolytic virus therapy: A new era of cancer treatment at dawn.

ABSTRACT: Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. T-Vec (talimogene laherparepvec), a second-generation oncolytic herpes simplex virus type 1 (HSV-1) armed with GM-CSF, was recently approved as the first oncolytic virus drug in the USA and Europe. The phase III trial proved that local intralesional injections with T-Vec in advanced malignant melanoma patients can not only suppress the growth of injected tumors but also act systemically and prolong overall survival. Other oncolytic viruses that are closing in on drug approval in North America and Europe include vaccinia virus JX-594 (pexastimogene devacirepvec) for hepatocellular carcinoma, GM-CSF-expressing adenovirus CG0070 for bladder cancer, and Reolysin (pelareorep), a wild-type variant of reovirus, for head and neck cancer. In Japan, a phase II clinical trial of G47?, a third-generation oncolytic HSV-1, is ongoing in glioblastoma patients. G47? was recently designated as a "Sakigake" breakthrough therapy drug in Japan. This new system by the Japanese government should provide G47? with priority reviews and a fast-track drug approval by the regulatory authorities. Whereas numerous oncolytic viruses have been subjected to clinical trials, the common feature that is expected to play a major role in prolonging the survival of cancer patients is an induction of specific antitumor immunity in the course of tumor-specific viral replication. It appears that it will not be long before oncolytic virus therapy becomes a standard therapeutic option for all cancer patients.

SUBMITTER: Fukuhara H

PROVIDER: S-EPMC5084676 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Oncolytic virus therapy: A new era of cancer treatment at dawn.

Fukuhara Hiroshi H Ino Yasushi Y Todo Tomoki T

Cancer science 20160909 10

Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. T-Vec (talimogene laherparepvec), a second-generation oncolytic herpes simplex virus type 1 (HSV-1) armed with GM-CSF, was recently approved as the first oncolytic vir ...[more]

PMID: 27486853

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Project description:During their development and progression tumors acquire numerous mutations that, when translated into proteins give rise to neoantigens that can be recognized by T cells. Initially, neoantigens were not recognized as preferred targets for cancer immunotherapy due to their enormous diversity and the therefore limited options to develop "one fits all" pharmacologic solutions. In recent years, the experience obtained in clinical trials demonstrating a predictive role of neoantigens in checkpoint inhibition has changed our view on the clinical potential of neoantigens in cancer immunotherapy. Technological advances such as sequencing of whole cancer genomes, the development of reliable algorithms for epitope prediction, and an increasing number of immunotherapeutic options now facilitate the development of personalized tumor therapies directly targeting a patient's neoantigenic burden. Preclinical studies in mice that support the excellent therapeutic potential of neoantigen-directed immunotherapies have provided blueprints on how this methodology can be translated into clinical applications in humans. Consistently, very recent clinical studies on personalized vaccinations targeting in silico predicted neoepitopes shed a first light on the therapeutic potential of personalized, neoantigen-directed immunotherapies. In our review, we discuss the various subtypes of tumor antigens with a focus on neoantigens and their potential in cancer immunotherapy. We will describe the current methods and techniques of detection as well as the structural requirements for neoantigens that are needed for their recognition by T cells and for tumor destruction. To assess the clinical potential of neoantigens, we will discuss their occurrence and functional relevance in spontaneous and hereditary cancers and their prognostic and predictive value. We will present in detail the existing immunotherapeutic options that exploit the neoantigen burden of tumors encompassing both preclinical efforts that provided convincing technological proof-of-concept and the current clinical studies confirming the potential of neoantigen-directed immunotherapies.

Project description:BackgroundCommunity health workers (CHWs) can play a critical role in primary healthcare and are seen widely as important to achieving the health-related Sustainable Development Goals (SDGs). The COVID-19 pandemic has emphasized the key role of CHWs. Improving how CHW programmes are governed is increasingly recognized as important for achieving universal access to healthcare and other health-related goals. This paper, the third in a series on "Community Health Workers at the Dawn of a New Era", aims to raise critical questions that decision-makers need to consider for governing CHW programmes, illustrate the options for governance using examples of national CHW programmes, and set out a research agenda for understanding how CHW programmes are governed and how this can be improved.MethodsWe draw from a review of the literature as well as from the knowledge and experience of those involved in the planning and management of CHW programmes.ResultsGoverning comprises the processes and structures through which individuals, groups, programmes, and organizations exercise rights, resolve differences, and express interests. Because CHW programmes are located between the formal health system and communities, and because they involve a wide range of stakeholders, their governance is complex. In addition, these programmes frequently fall outside of the governance structures of the formal health system or are poorly integrated with it, making governing these programmes more challenging. We discuss the following important questions that decision-makers need to consider in relation to governing CHW programmes: (1) How and where within political structures are policies made for CHW programmes? (2) Who implements decisions regarding CHW programmes and at what levels of government? (3) What laws and regulations are needed to support the programme? (4) How should the programme be adapted across different settings or groups within the country or region?ConclusionThe most appropriate and acceptable models for governing CHW programmes depend on communities, on local health systems, and on the political system in which the programme is located. Stakeholders in each setting need to consider what systems are currently in place and how they might be adapted to local needs and systems.

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Oncolytic virus therapy: A new era of cancer treatment at dawn.

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Oncolytic virus therapy: A new era of cancer treatment at dawn.

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