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Frontiers in Immunology 2022Oncolytic Viruses (OVs) work through two main mechanisms of action: the direct lysis of the virus-infected cancer cells and the release of tumor antigens as a result of...
Oncolytic Viruses (OVs) work through two main mechanisms of action: the direct lysis of the virus-infected cancer cells and the release of tumor antigens as a result of the viral burst. In this sc.enario, the OVs act as cancer vaccines, since the immunogenicity of the virus is combined with tumor antigens, that direct the specificity of the anti-tumor adaptive immune response. However, this mechanism in some cases fails in eliciting a strong specific T cell response. One way to overcome this problem and enhance the priming efficiency is the production of genetically modified oncolytic viruses encoding one or more tumor antigens. To avoid the long and expensive process related to the engineering of the OVs, we have exploited an approach based on coating OVs (adenovirus and vaccinia virus) with tumor antigens. In this work, oncolytic viruses encoding tumor antigens and tumor antigen decorated adenoviral platform (PeptiCRAd) have been used as cancer vaccines and evaluated both for their prophylactic and therapeutic efficacy. We have first tested the oncolytic vaccines by exploiting the OVA model, moving then to TRP2, a more clinically relevant tumor antigen. Finally, both approaches have been investigated in tumor neo-antigens settings. Interestingly, both genetically modified oncolytic adenovirus and PeptiCRAd elicited T cells-specific anti-tumor responses. However, cross-representation experiments, showed an advantage of PeptiCRAd as regards the fast presentation of the model epitope SIINFEKL from OVA in an immunogenic rather than tolerogenic fashion. Here two approaches used as cancer oncolytic vaccines have been explored and characterized for their efficacy. Although the generation of specific anti-tumor T cells was elicited in both approaches, PeptiCRAd retains the advantage of being rapidly adaptable by coating the adenovirus with a different set of tumor antigens, which is crucial in personalized cancer vaccines clinical setting.
Topics: Adenoviridae; Antigens, Neoplasm; Cancer Vaccines; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Peptides; Precision Medicine; Vaccines, Subunit
PubMed: 35493448
DOI: 10.3389/fimmu.2022.826164 -
Expert Opinion on Drug Discovery Apr 2021: Despite diverse treatment modalities and novel therapies, many cancers and patients are not effectively treated. Cancer immunotherapy has recently achieved... (Review)
Review
: Despite diverse treatment modalities and novel therapies, many cancers and patients are not effectively treated. Cancer immunotherapy has recently achieved breakthrough status yet is not effective in all cancer types or patients and can generate serious adverse effects. Oncolytic viruses (OVs) are a promising new therapeutic modality that harnesses virus biology and host interactions to treat cancer. OVs, genetically engineered or natural, preferentially replicate in and kill cancer cells, sparing normal cells/tissues, and mediating anti-tumor immunity.: This review focuses on OVs as cancer therapeutic agents from a historical perspective, especially strategies to boost their immunotherapeutic activities. OVs offer a multifaceted platform, whose activities are modulated based on the parental virus and genetic alterations. In addition to direct viral effects, many OVs can be armed with therapeutic transgenes to also act as gene therapy vectors, and/or combined with other drugs or therapies.: OVs are an amazingly versatile and malleable class of cancer therapies. They tend to target cellular and host physiology as opposed to specific genetic alterations, which potentially enables broad responsiveness. The biological complexity of OVs have hindered their translation; however, the recent approval of talimogene laherparepvec (T-Vec) has invigorated the field.
Topics: Animals; Antineoplastic Agents, Immunological; Biological Products; Herpesvirus 1, Human; Humans; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 33232188
DOI: 10.1080/17460441.2021.1850689 -
Cytokine & Growth Factor Reviews Dec 2020Cancer immunotherapy using tumor-selective, oncolytic viruses is an emerging therapeutic option for solid and hematologic malignancies. A considerable variety of viruses... (Review)
Review
Cancer immunotherapy using tumor-selective, oncolytic viruses is an emerging therapeutic option for solid and hematologic malignancies. A considerable variety of viruses ranging from small picornaviruses to large poxviruses are currently being investigated as potential candidates. In the early days of virotherapy, non-engineered wild-type or vaccine-strain viruses were employed. However, these viruses often did not fully satisfy the major criteria of safety and efficacy. Since the advent of reverse genetics systems for manipulating various classes of viruses, the field has shifted to developing genetically engineered viruses with an improved therapeutic index. In this review, we will summarize the concepts and strategies of multi-level genetic engineering of oncolytic measles virus, a prime candidate for cancer immunovirotherapy. Furthermore, we will provide a brief overview of measles virus-based multimodal combination therapies for improved tumor control and clinical efficacy.
Topics: Humans; Immunotherapy; Measles virus; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 32718830
DOI: 10.1016/j.cytogfr.2020.07.005 -
Biomedicine & Pharmacotherapy =... Dec 2023Tumors of the gastrointestinal tract impose a substantial healthcare burden due to their prevalence and challenging prognosis. (Review)
Review
BACKGROUND
Tumors of the gastrointestinal tract impose a substantial healthcare burden due to their prevalence and challenging prognosis.
METHODS
We conducted a review of peer-reviewed scientific literature using reputable databases (PubMed, Scopus, Web of Science) with a focus on oncolytic virus therapy within the context of gastrointestinal tumors. Our search covered the period up to the study's completion in June 2023.
INCLUSION AND EXCLUSION CRITERIA
This study includes articles from peer-reviewed scientific journals, written in English, that specifically address oncolytic virus therapy for gastrointestinal tumors, encompassing genetic engineering advances, combined therapeutic strategies, and safety and efficacy concerns. Excluded are articles not meeting these criteria or focusing on non-primary gastrointestinal metastatic tumors.
RESULTS
Our review revealed the remarkable specificity of oncolytic viruses in targeting tumor cells and their potential to enhance anti-tumor immune responses. However, challenges related to safety and efficacy persist, underscoring the need for ongoing research and improvement.
CONCLUSION
This study highlights the promising role of oncolytic virus therapy in enhancing gastrointestinal tumor treatments. Continued investigation and innovative combination therapies hold the key to reducing the burden of these tumors on patients and healthcare systems.
Topics: Humans; Oncolytic Virotherapy; Oncolytic Viruses; Neoplasms; Gastrointestinal Neoplasms; Genetic Engineering; Immunotherapy
PubMed: 37812894
DOI: 10.1016/j.biopha.2023.115627 -
Thoracic Cancer May 2019Oncolytic viruses (OVs) are promising new therapeutic agents in the field of malignant tumor treatment. OVs can achieve the goal of targeted therapy by selectively... (Review)
Review
Oncolytic viruses (OVs) are promising new therapeutic agents in the field of malignant tumor treatment. OVs can achieve the goal of targeted therapy by selectively killing tumor cells and inducing specific antitumor immunity. The key roles of OVs are tumor targeting and tumor killing mechanisms. Recently, molecular biotechnology has been used to optimize the transformation of wild virus strains in order to ensure a stronger oncolytic effect and lower adverse reactions, to enable testing in clinical trials as an antitumor drug. The main purpose of this review is to provide a description of oncolytic mechanisms, clinical studies, combination therapies, current challenges, and future prospects of OVs.
Topics: Animals; Biomarkers, Tumor; Clinical Studies as Topic; Combined Modality Therapy; Disease Susceptibility; Genetic Vectors; Humans; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Treatment Outcome
PubMed: 30900824
DOI: 10.1111/1759-7714.13043 -
Journal For Immunotherapy of Cancer Nov 2017With the approval of talimogene laherparepvec (T-VEC) for inoperable locally advanced or metastatic malignant melanoma in the USA and Europe, oncolytic virotherapy is... (Review)
Review
With the approval of talimogene laherparepvec (T-VEC) for inoperable locally advanced or metastatic malignant melanoma in the USA and Europe, oncolytic virotherapy is now emerging as a viable therapeutic option for cancer patients. In parallel, following the favourable results of several clinical trials, adoptive cell transfer using chimeric antigen receptor (CAR)-redirected T-cells is anticipated to enter routine clinical practice for the management of chemotherapy-refractory B-cell malignancies. However, CAR T-cell therapy for patients with advanced solid tumours has proved far less successful. This Review draws upon recent advances in the design of novel oncolytic viruses and CAR T-cells and provides a comprehensive overview of the synergistic potential of combination oncolytic virotherapy with CAR T-cell adoptive cell transfer for the management of solid tumours, drawing particular attention to the methods by which recombinant oncolytic viruses may augment CAR T-cell trafficking into the tumour microenvironment, mitigate or reverse local immunosuppression and enhance CAR T-cell effector function and persistence.
Topics: Adoptive Transfer; Female; Humans; Male; Oncolytic Viruses; Receptors, Antigen, T-Cell
PubMed: 29157300
DOI: 10.1186/s40425-017-0294-6 -
Cancer Research Communications Jun 2023Oncolytic viruses exploited for cancer therapy have been developed to selectively infect, replicate, and kill cancer cells to inhibit tumor growth. However, in some...
UNLABELLED
Oncolytic viruses exploited for cancer therapy have been developed to selectively infect, replicate, and kill cancer cells to inhibit tumor growth. However, in some cancer cells, oncolytic viruses are often limited in completing their full replication cycle, forming progeny virions, and/or spreading in the tumor bed because of the heterogeneous cell types within the tumor bed. Here, we report that the nuclear export pathway regulates oncolytic myxoma virus (MYXV) infection and cytoplasmic viral replication in a subclass of human cancer cell types where viral replication is restricted. Inhibition of the XPO-1 (exportin 1) nuclear export pathway with nuclear export inhibitors can overcome this restriction by trapping restriction factors in the nucleus and allow significantly enhanced viral replication and killing of cancer cells. Furthermore, knockdown of XPO-1 significantly enhanced MYXV replication in restrictive human cancer cells and reduced the formation of antiviral granules associated with RNA helicase DHX9. Both and , we demonstrated that the approved XPO1 inhibitor drug selinexor enhances the replication of MYXV and kills diverse human cancer cells. In a xenograft tumor model in NSG mice, combination therapy with selinexor plus MYXV significantly reduced the tumor burden and enhanced the survival of animals. In addition, we performed global-scale proteomic analysis of nuclear and cytosolic proteins in human cancer cells to identify the host and viral proteins that were upregulated or downregulated by different treatments. These results indicate, for the first time, that selinexor in combination with oncolytic MYXV can be used as a potential new therapy.
SIGNIFICANCE
We demonstrated that a combination of nuclear export inhibitor selinexor and oncolytic MYXV significantly enhanced viral replication, reduced cancer cell proliferation, reduced tumor burden, and enhanced the overall survival of animals. Thus, selinexor and oncolytic MYXV can be used as potential new anticancer therapy.
Topics: Humans; Animals; Mice; Myxoma virus; Active Transport, Cell Nucleus; Proteomics; Neoplasms; Oncolytic Viruses
PubMed: 37377603
DOI: 10.1158/2767-9764.CRC-22-0483 -
Biomedicine & Pharmacotherapy =... Jul 2021The incidence of hematological malignancies such as multiple myeloma, leukemia, and lymphoma has increased over time. Although bone marrow transplantation, immunotherapy... (Review)
Review
The incidence of hematological malignancies such as multiple myeloma, leukemia, and lymphoma has increased over time. Although bone marrow transplantation, immunotherapy and chemotherapy have led to significant improvements in efficacy, poor prognosis in elderly patients, recurrence and high mortality among hematological malignancies remain major challenges, and innovative therapeutic strategies should be explored. Besides directly lyse tumor cells, oncolytic viruses can activate immune responses or be engineered to express therapeutic factors to increase antitumor efficacy, and have gradually been recognized as an appealing approach for fighting cancers. An increasing number of studies have applied oncolytic viruses in hematological malignancies and made progress. In particular, strategies combining immunotherapy and oncolytic virotherapy are emerging. Various phase I clinical trials of oncolytic reovirus with lenalidomide or programmed death 1(PD-1) immune checkpoint inhibitors in multiple myeloma are ongoing. Moreover, preclinical studies of combinations with chimeric antigen receptor T (CAR-T) cells are underway. Thus, oncolytic virotherapy is expected to be a promising approach to cure hematological malignancies. This review summarizes progress in oncolytic virus research in hematological malignancies. After briefly reviewing the development and oncolytic mechanism of oncolytic viruses, we focus on delivery methods of oncolytic viruses, especially systemic delivery that is suitable for hematological tumors. We then discuss the main types of oncolytic viruses applied for hematological malignancies and related clinical trials. In addition, we present several ways to improve the antitumor efficacy of oncolytic viruses. Finally, we discuss current challenges and provide suggestions for future studies.
Topics: Animals; Combined Modality Therapy; Hematologic Neoplasms; Humans; Immunotherapy; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 33894623
DOI: 10.1016/j.biopha.2021.111573 -
Cell Death & Disease Jun 2020Glioblastoma (GBM) is an immunosuppressive, lethal brain tumor. Despite advances in molecular understanding and therapies, the clinical benefits have remained limited,... (Review)
Review
Glioblastoma (GBM) is an immunosuppressive, lethal brain tumor. Despite advances in molecular understanding and therapies, the clinical benefits have remained limited, and the life expectancy of patients with GBM has only been extended to ~15 months. Currently, genetically modified oncolytic viruses (OV) that express immunomodulatory transgenes constitute a research hot spot in the field of glioma treatment. An oncolytic virus is designed to selectively target, infect, and replicate in tumor cells while sparing normal tissues. Moreover, many studies have shown therapeutic advantages, and recent clinical trials have demonstrated the safety and efficacy of their usage. However, the therapeutic efficacy of oncolytic viruses alone is limited, while oncolytic viruses expressing immunomodulatory transgenes are more potent inducers of immunity and enhance immune cell-mediated antitumor immune responses in GBM. An increasing number of basic studies on oncolytic viruses encoding immunomodulatory transgene therapy for malignant gliomas have yielded beneficial outcomes. Oncolytic viruses that are armed with immunomodulatory transgenes remain promising as a therapy against malignant gliomas and will undoubtedly provide new insights into possible clinical uses or strategies. In this review, we summarize the research advances related to oncolytic viruses that express immunomodulatory transgenes, as well as potential treatment pitfalls in patients with malignant gliomas.
Topics: Animals; Brain Neoplasms; Genetic Therapy; Glioma; Humans; Immunomodulation; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 32587256
DOI: 10.1038/s41419-020-2696-5 -
EBioMedicine Jul 2016Oncolytic viruses (OV) are replicating viral therapeutics for the treatment of cancer and have been in laboratory development for about twenty years. Recently, the FDA... (Review)
Review
Oncolytic viruses (OV) are replicating viral therapeutics for the treatment of cancer and have been in laboratory development for about twenty years. Recently, the FDA approved Imlygic, a herpes virus based therapeutic for the treatment of melanoma and thus OVs have entered a new era where they are a weapon in the armament of the oncologist. OVs are unique therapeutics with multiple mechanisms of therapeutic activity. The exact path for their development and eventual uptake by pharmaceutical companies is somewhat clouded by an uncertain identity. Are they vaccines, tumour lysing therapeutics, inducers of innate immunity, gene therapy vectors, anti-vascular agents or all of the above? Should they be developed as stand-alone loco-regional therapeutics, systemically delivered tumour hunters or immune modulators best tested as combination therapeutics? We summarize data here supporting the idea, depending upon the virus, that OVs can be any or all of these things. Pursuing a "one-size fits all" approach is counter-productive to their clinical development and instead as a field we should build on the strengths of individual virus platforms.
Topics: Animals; Cancer Vaccines; Clinical Trials as Topic; Genetic Therapy; Genetic Vectors; Humans; Immunomodulation; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Treatment Outcome; Tumor Microenvironment
PubMed: 27407036
DOI: 10.1016/j.ebiom.2016.06.046