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Introduction to Cells, DNA, and Viruses
Published in Patricia G. Melloy, Viruses and Society, 2023
In addition, scientists are trying to harness viruses to treat cancer. Oncolytic viruses have been known for over a hundred years but are not well understood. These viruses can attack cancer cells as well as mobilize other parts of the immune system by their presence, leading to immune cells going after the cancer cells as well. Studies are underway on the use of “virotherapy” as an additional treatment option for cancers like multiple myeloma (Brown 2020).
Malignant Melanoma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Oncolytic virotherapy is an emerging treatment modality whereby replicating viruses can be used to selectively replicate within tumors to enhance local and systemic immune responses promoting tumor regression. The phase III OPTiM trial of an oncolytic herpes simplex virus vector (talimogene laherparepvec T-VEC) encoding GM-CSF vs. GM-CSF was carried out in a total of 436 patients with stage III/IV melanoma. The T-VEC vaccine was injected intra-lesionally whereas GM-CSF was administered subcutaneously. Data from the final analysis of the trial showed that the response rate for intralesional T-VEC vaccination was 31.5% compared to 6.4% for the GM-CSF groups. Overall survival analysis favored T-VEC vaccine with a hazard ration of 0.79 and p value = 0.0494.23
Malignant melanoma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2014
Kroopa Joshi, James Larkin, Martin Gore
Oncolytic virotherapy is an emerging treatment modality whereby replicating viruses can be used to selectively replicate within tumours to enhance local and systemic immune responses promoting tumour regression. A phase III trial of an oncolytic herpes simplex virus vector (talimogene laherparepvec T-VEC) encoding GM-CSF versus GM-CSF was carried out in a total of 436 patients with stage III/IV melanoma. The T-VEC vaccine was injected intra-lesionally whereas GM-CSF was administered subcutaneously. Data presented at American Society of Clinical Oncology (ASCO) 2013 showed that the response rate for intralesional T-VEC vaccination was 26% compared to 2% for the GM-CSF groups. Interim overall survival anaylsis showed a trend in favour of the T-VEC vaccine although this was not statistically significant.
Locked and loaded: engineering and arming oncolytic adenoviruses to enhance anti-tumor immune responses
Published in Expert Opinion on Biological Therapy, 2022
Oncolytic viruses are a novel class of self-amplifying therapeutic agents that have the natural ability to replicate in and kill cancer cells (reviewed in [1,2]). The original concept of oncolytic viruses is that their efficacy would come from killing primary and disseminated cancers by direct cell lysis. While this does occur, preclinical and clinical data suggest that much of the efficacy of virotherapy may actually arise from their ability to ‘make tumors hot’ or activate the immune system against cancer cells [3,4]. This ability to increase inflammation in tumors comes in part from viral replication of DNA, RNA, and proteins that can be recognized as pathogen-associated molecular patterns (PAMPs) to activate immune cells [3]. Direct viral lysis can also induce immunogenic cell death (ICD) through the release of cellular contents that be recognized as damage-associated molecular patterns (DAMPs) to activate immune cells [3]. Both PAMPs and DAMPs can trigger the secretion of pro-inflammatory cytokines and establish an anti-tumor immunological environment in the tumors. Direct viral lysis can also assist in exposing cancer antigens to antigen-presenting cells (APCs) like macrophages and dendritic cells (DCs) to trigger anti-tumor immunity [3].
Merits of the ‘good’ viruses: the potential of virus-based therapeutics
Published in Expert Opinion on Biological Therapy, 2021
Qianyu Zhang, Wen Wu, Jinqiang Zhang, Xuefeng Xia
Virotherapy refers to treating tumors with bioengineered oncolytic viruses. The relationship between virus infection or vaccination and certain cases of tumor remission has long been intricate [21]. Some early clinical publications provided case reports describing the coincidence of tumor regressions with natural viral infections during the past century, with most of the patients suffering from hematological malignancies such as leukemia or lymphoma [22]. Later during the 1950s to the 1980s, researchers started clinical case studies using attenuated, non-engineered viruses for cancer management [23–37]. Viruses including West Nile Virus, mumps virus, adenovirus, Newcastle Disease Virus, vaccinia virus were applied in treating cancers such as leukemia, Hodgkin’s disease, Burkitt lymphoma, cervix carcinoma, metastatic melanoma, adenocarcinoma, myeloma et al. These viruses seemed to be related to the tumor regression in the case studies. However, some of these remissions were known to be short-lived, while some patients were rendered free of disease years after treatment (such as advanced melanoma patients treated with vaccinia) [30].
A tool with many applications: vesicular stomatitis virus in research and medicine
Published in Expert Opinion on Biological Therapy, 2020
Altar M. Munis, Emma M. Bentley, Yasuhiro Takeuchi
We predict there will be more effort in developing replication-competent VSV-based viral vaccines following the successful use of rVSV-ZEBOV. The attraction of vectored vaccine approaches is the relative ease of design and large-scale manufacture of recombinant virus constructs incorporating the sequence of target envelope proteins. In particular, rVSV has been shown to elicit strong humoral and cellular responses and has a low seroprevalence in the human population. As a relatively new player in the vectored vaccine field, the completion of recent and ongoing phase I–III human clinical trials will help to realize the full potential of this platform; paving the way for other candidates in preclinical stages of development. In contrast, the application of VSV for oncolytic virotherapy will face challenges before its efficacy is fully demonstrated preclinically and it reaches clinics. VSV seems to have less tight cancer tropism compared to many other oncolytic viruses in clinical use or under development. For both vaccine and oncolytic purposes, the safety and regulatory issues are paramount for the use of replication-competent viruses. For example in the UK vesicular stomatitis is under a tight control by The Department for Environment, Food and Rural Affairs (DEFRA) and is a notifiable animal disease [239] and VSV is covered by Specific Animal Pathogen Order (SAPO) [240].