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Frontiers in Pharmacology 2024Compared to other cancer immunotherapies, oncolytic viruses possess several advantages, including high killing efficiency, excellent targeting capabilities, minimal... (Review)
Review
Compared to other cancer immunotherapies, oncolytic viruses possess several advantages, including high killing efficiency, excellent targeting capabilities, minimal adverse reactions, and multiple pathways for tumor destruction. However, the efficacy of oncolytic viruses as a monotherapy often falls short of expectations. Consequently, combining oncolytic viruses with traditional treatments to achieve synergistic effects has emerged as a promising direction for the development of oncolytic virus therapies. This article provides a comprehensive review of the current progress in preclinical and clinical trials exploring the combination therapies involving oncolytic viruses. Specifically, we discuss the combination of oncolytic viruses with immune checkpoint inhibitors, chemotherapy, targeted therapy, and cellular therapy. The aim of this review is to offer valuable insights and references for the further advancement of these combination strategies in clinical applications. Further research is necessary to refine the design of combination therapies and explore novel strategies to maximize the therapeutic benefits offered by oncolytic viruses.
PubMed: 38725667
DOI: 10.3389/fphar.2024.1380313 -
Molecular Therapy : the Journal of the... Nov 2023In recent years, there has been a surge in the innovative modification and application of the viral vector-based gene therapy field. Significant and consistent... (Review)
Review
In recent years, there has been a surge in the innovative modification and application of the viral vector-based gene therapy field. Significant and consistent improvements in the engineering, delivery, and safety of viral vectors have set the stage for their application as RNA interference (RNAi) delivery tools. Viral vector-based delivery of RNAi has made remarkable breakthroughs in the treatment of several debilitating diseases and disorders (e.g., neurological diseases); however, their novelty has yet to be fully applied and utilized for the treatment of cancer. This review highlights the most promising and emerging viral vector delivery tools for RNAi therapeutics while discussing the variables limiting their success and suitability for cancer therapy. Specifically, we outline different integrating and non-integrating viral platforms used for gene delivery, currently employed RNAi targets for anti-cancer effect, and various strategies used to optimize the safety and efficacy of these RNAi therapeutics. Most importantly, we provide great insight into what challenges exist in their application as cancer therapeutics and how these challenges can be effectively navigated to advance the field.
Topics: RNA Interference; Genetic Vectors; Genetic Therapy; Gene Transfer Techniques; Neoplasms
PubMed: 37735876
DOI: 10.1016/j.ymthe.2023.09.012 -
Journal of Translational Medicine Jul 2023Oncolytic virotherapy (OVT) is a promising anti-tumor modality that utilizes oncolytic viruses (OVs) to preferentially attack cancers rather than normal tissues. With... (Review)
Review
BACKGROUND
Oncolytic virotherapy (OVT) is a promising anti-tumor modality that utilizes oncolytic viruses (OVs) to preferentially attack cancers rather than normal tissues. With the understanding particularly in the characteristics of viruses and tumor cells, numerous innovative OVs have been engineered to conquer cancers, such as Talimogene Laherparepvec (T-VEC) and tasadenoturev (DNX-2401). However, the therapeutic safety and efficacy must be further optimized and balanced to ensure the superior safe and efficient OVT in clinics, and reasonable combination therapy strategies are also important challenges worthy to be explored.
MAIN BODY
Here we provided a critical review of the development history and status of OVT, emphasizing the mechanisms of enhancing both safety and efficacy. We propose that oncolytic virotherapy has evolved into the fourth generation as tumor immunotherapy. Particularly, to arouse T cells by designing OVs expressing bi-specific T cell activator (BiTA) is a promising strategy of killing two birds with one stone. Amazing combination of therapeutic strategies of OVs and immune cells confers immense potential for managing cancers. Moreover, the attractive preclinical OVT addressed recently, and the OVT in clinical trials were systematically reviewed.
CONCLUSION
OVs, which are advancing into clinical trials, are being envisioned as the frontier clinical anti-tumor agents coming soon.
Topics: Humans; Oncolytic Virotherapy; Melanoma; Oncolytic Viruses; Neoplasms; Immunotherapy; Combined Modality Therapy
PubMed: 37491263
DOI: 10.1186/s12967-023-04360-8 -
Cancer Letters Mar 2024Breast cancer continues to pose significant challenges in the field of oncology, necessitating innovative treatment approaches. Among these, oncolytic viruses have... (Review)
Review
Breast cancer continues to pose significant challenges in the field of oncology, necessitating innovative treatment approaches. Among these, oncolytic viruses have emerged as a promising frontier in the battle against various types of cancer, including breast cancer. These viruses, often genetically modified, have the unique ability to selectively infect and destroy cancer cells while leaving healthy cells unharmed. Their efficacy in tumor eradication is not only owing to direct cell lysis but also relies on their capacity to activate the immune system, thereby eliciting a potent and sustained antitumor response. While oncolytic viruses represent a significant advancement in cancer treatment, the complexity and adaptability inherent to cancer require a diverse array of therapies. The concept of combining oncolytic viruses with other treatment modalities, such as chemotherapy, immunotherapy, and targeted therapies, has received significant attention. This synergistic approach capitalizes on the strengths of each therapy, thus creating a comprehensive strategy to tackle the heterogeneous and evolving nature of breast cancer. The purpose of this review is to provide an in-depth discussion of preclinical and clinical viro-based combination therapy in the context of breast cancer.
Topics: Humans; Female; Breast Neoplasms; Oncolytic Viruses; Oncolytic Virotherapy; Neoplasms; Immunotherapy; Combined Modality Therapy
PubMed: 38309616
DOI: 10.1016/j.canlet.2024.216634 -
Cancer Letters Jun 2024Oncolytic viruses (OVs) represent an emerging immunotherapeutic strategy owing to their capacity for direct tumor lysis and induction of antitumor immunity. However,... (Review)
Review
Oncolytic viruses (OVs) represent an emerging immunotherapeutic strategy owing to their capacity for direct tumor lysis and induction of antitumor immunity. However, hurdles like transient persistence and moderate efficacy necessitate innovative approaches. Metabolic remodeling has recently gained prominence as a strategic intervention, wherein OVs or combination regimens could reprogram tumor and immune cell metabolism to enhance viral replication and oncolysis. In this review, we summarize recent advances in strategic reprogramming of tumor and immune cell metabolism to enhance OV-based immunotherapies. Specific tactics include engineering viruses to target glycolytic, glutaminolytic, and nucleotide synthesis pathways in cancer cells, boosting viral replication and tumor cell death. Additionally, rewiring T cell and NK cell metabolism of lipids, amino acids, and carbohydrates shows promise to enhance antitumor effects. Further insights are discussed to pave the way for the clinical implementation of metabolically enhanced oncolytic platforms, including balancing metabolic modulation to limit antiviral responses while promoting viral persistence and tumor clearance.
Topics: Humans; Oncolytic Virotherapy; Neoplasms; Oncolytic Viruses; Animals; Virus Replication; Immunotherapy; T-Lymphocytes; Killer Cells, Natural
PubMed: 38718886
DOI: 10.1016/j.canlet.2024.216924 -
Journal For Immunotherapy of Cancer Aug 2023Triple-negative breast cancer (TNBC) corresponds to approximately 20% of all breast tumors, with a high propensity for metastasis and a poor prognosis. Because TNBC...
BACKGROUND
Triple-negative breast cancer (TNBC) corresponds to approximately 20% of all breast tumors, with a high propensity for metastasis and a poor prognosis. Because TNBC displays a high mutational load compared with other breast cancer types, a neoantigen-based immunotherapy strategy could be effective. One major bottleneck in the development of a neoantigen-based vaccine for TNBC is the selection of the best targets, that is, tumor-specific neoantigens which are presented at the surface of tumor cells and capable of eliciting robust immune responses. In this study, we aimed to set up a platform for identification and delivery of immunogenic neoantigens in a vaccine regimen for TNBC using oncolytic vaccinia virus (VV).
METHODS
We used bioinformatic tools and cell-based assays to identify immunogenic neoantigens in TNBC patients' samples, human and murine cell lines. Immunogenicity of the neoantigens was tested in vitro (human) and ex vivo (murine) in T-cell assays. To assess the efficacy of our regimen, we used a preclinical model of TNBC where we treated tumor-bearing mice with neoantigens together with oncolytic VV and evaluated the effect on induction of neoantigen-specific CD8+T cells, tumor growth and survival.
RESULTS
We successfully identified immunogenic neoantigens and generated neoantigen-specific CD8+T cells capable of recognizing a human TNBC cell line expressing the mutated gene. Using a preclinical model of TNBC, we showed that our tumor-specific oncolytic VV was able to change the tumor microenvironment, attracting and maintaining mature cross-presenting CD8α+dendritic cells and effector T-cells. Moreover, when delivered in a prime/boost regimen together with oncolytic VV, long peptides encompassing neoantigens were able to induce neoantigen-specific CD8+T cells, slow tumor growth and increase survival.
CONCLUSIONS
Our study provides a promising approach for the development of neoantigen-based immunotherapies for TNBC. By identifying immunogenic neoantigens and developing a delivery system through tumor-specific oncolytic VV, we have demonstrated that neoantigen-based vaccines could be effective in inducing neoantigen-specific CD8+T cells response with significant impact on tumor growth. Further studies are needed to determine the safety and efficacy of this approach in clinical trials.
Topics: Humans; Animals; Mice; Triple Negative Breast Neoplasms; Vaccinia virus; Biological Assay; CD8-Positive T-Lymphocytes; Immunotherapy; Oncolytic Viruses; Tumor Microenvironment
PubMed: 37586771
DOI: 10.1136/jitc-2023-007336 -
Medical Oncology (Northwood, London,... Jul 2023Cancer treatment is one of the most challenging topics in medical sciences. Different methods such as chemotherapy, tumor surgery, and immune checkpoint inhibitors... (Review)
Review
Cancer treatment is one of the most challenging topics in medical sciences. Different methods such as chemotherapy, tumor surgery, and immune checkpoint inhibitors therapy (ICIs) are potential approaches to treating cancer and killing tumor cells, but clinical studies have shown that they have been successful for a limited group of patients. Using viruses as a treatment can be considered as an effective treatment in the field of medicine. This is considered as a potential treatment, especially in comparison to chemotherapy, which has severe side effects related to the immune system. Most oncolytic viruses (OVs) have the potential to multiply in cancer cells, which are more than normal cells in malignant tissue and can induce immune responses. Therefore, tons of efforts and research have been started on the utilization of OVs as a treatment for cancer and have shown promising in treating cancers with less side effects. In this article, we have gathered studies about oncolytic viruses and their effectiveness in cancer treatment.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [Omid Salahi] Last name [Ardekani], Author 2 Given name: [Mohammad Mehdi] Last name [Fazeli], Author 3 Given name: [Nillofar Asadi] Last name [Jemezghani]. Also, kindly confirm the details in the metadata are correct.Confirmed.
Topics: Humans; Oncolytic Viruses; Oncolytic Virotherapy; Delusions; Neoplasms; Treatment Outcome; Drug-Related Side Effects and Adverse Reactions
PubMed: 37458862
DOI: 10.1007/s12032-023-02106-6 -
Current Issues in Molecular Biology Jun 2024The recent success of cancer immunotherapies, such as immune checkpoint inhibitor (ICIs), monoclonal antibodies (mAbs), cancer vaccines, and adoptive cellular therapies... (Review)
Review
The recent success of cancer immunotherapies, such as immune checkpoint inhibitor (ICIs), monoclonal antibodies (mAbs), cancer vaccines, and adoptive cellular therapies (ACTs), has revolutionized traditional cancer treatment. However, these immunotherapeutic modalities have variable efficacies, and many of them exhibit adverse effects. Oncolytic viral Immunotherapy (OViT), whereby viruses are used to directly or indirectly induce anti-cancer immune responses, is emerging as a novel immunotherapy for treating patients with different types of cancer. The herpes simplex virus type-1 (HSV-1) possesses many characteristics that inform its use as an effective OViT agents and remains a leading candidate. Its recent clinical success resulted in the Food and Drug Administration (FDA) approval of Talimogene laherparevec (T-VEC or Imlygic) in 2015 for the treatment of advanced melanoma. In this review, we discuss recent advances in the development of oncolytic HSV-1-based OViTs, their anti-tumor mechanism of action, and efficacy data from recent clinical trials. We envision this knowledge may be used to inform the rational design and application of future oHSV in cancer treatment.
PubMed: 38921005
DOI: 10.3390/cimb46060334 -
Cancer Biology & Medicine Aug 2023Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects systemic administration. Tumor cells often... (Review)
Review
Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects systemic administration. Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication; however, recent studies have established that viruses altered genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments. Specifically, oncolytic vaccinia virus (OVV) has gained popularity owing to its safety, potential for systemic delivery, and large gene insertion capacity. This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity and , and provides an overview of ongoing clinical trials and combination therapies. In addition, we discuss the potential benefits and drawbacks of OVV as a cancer therapy, and explore different perspectives in this field.
Topics: Humans; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Tumor Microenvironment; Vaccinia virus; Clinical Trials as Topic
PubMed: 37615308
DOI: 10.20892/j.issn.2095-3941.2023.0202 -
Journal Der Deutschen Dermatologischen... Apr 2024
PubMed: 38679789
DOI: 10.1111/ddg.15423