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Trends in Immunology May 2020In cancer immunotherapy, a patient's own immune system is harnessed against cancer. Immune checkpoint inhibitors release the brakes on tumor-reactive T cells and,... (Review)
Review
In cancer immunotherapy, a patient's own immune system is harnessed against cancer. Immune checkpoint inhibitors release the brakes on tumor-reactive T cells and, therefore, are particularly effective in treating certain immune-infiltrated solid tumors. By contrast, solid tumors with immune-silent profiles show limited efficacy of checkpoint blockers due to several barriers. Recent discoveries highlight transforming growth factor-β (TGF-β)-induced immune exclusion and a lack of immunogenicity as examples of these barriers. In this review, we summarize preclinical and clinical evidence that illustrates how the inhibition of TGF-β signaling and the use of oncolytic viruses (OVs) can increase the efficacy of immunotherapy, and discuss the promise and challenges of combining these approaches with immune checkpoint blockade.
Topics: Humans; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Transforming Growth Factor beta
PubMed: 32223932
DOI: 10.1016/j.it.2020.03.003 -
International Journal of Molecular... Dec 2022Self-replicating RNA viruses have become attractive delivery vehicles for therapeutic applications. They are easy to handle, can be rapidly produced in large quantities,... (Review)
Review
Self-replicating RNA viruses have become attractive delivery vehicles for therapeutic applications. They are easy to handle, can be rapidly produced in large quantities, and can be delivered as recombinant viral particles, naked or nanoparticle-encapsulated RNA, or plasmid DNA-based vectors. The self-replication of RNA in infected host cells provides the means for generating much higher transgene expression levels and the possibility to apply substantially reduced amounts of RNA to achieve similar expression levels or immune responses compared to conventional synthetic mRNA. Alphaviruses and flaviviruses, possessing a single-stranded RNA genome of positive polarity, as well as measles viruses and rhabdoviruses with a negative-stranded RNA genome, have frequently been utilized for therapeutic applications. Both naturally and engineered oncolytic self-replicating RNA viruses providing specific replication in tumor cells have been evaluated for cancer therapy. Therapeutic efficacy has been demonstrated in animal models. Furthermore, the safe application of oncolytic viruses has been confirmed in clinical trials. Multiple myeloma patients treated with an oncolytic measles virus (MV-NIS) resulted in increased T-cell responses against the measles virus and several tumor-associated antigen responses and complete remission in one patient. Furthermore, MV-CEA administration to patients with ovarian cancer resulted in a stable disease and more than doubled the median overall survival.
Topics: Humans; Animals; Female; Oncolytic Viruses; RNA; RNA Viruses; Ovarian Neoplasms; Measles virus; Oncolytic Virotherapy; Neoplasms
PubMed: 36555262
DOI: 10.3390/ijms232415622 -
Nature Communications May 2023Oncolytic adenovirus (Ad) infection promotes intracellular autophagy in tumors. This could kill cancer cells and contribute to Ads-mediated anticancer immunity. However,...
Oncolytic adenovirus (Ad) infection promotes intracellular autophagy in tumors. This could kill cancer cells and contribute to Ads-mediated anticancer immunity. However, the low intratumoral content of intravenously delivered Ads could be insufficient to efficiently activate tumor over-autophagy. Herein, we report bacterial outer membrane vesicles (OMVs)-encapsulating Ads as microbial nanocomposites that are engineered for autophagy-cascade-augmented immunotherapy. Biomineral shells cover the surface antigens of OMVs to slow their clearance during in vivo circulation, enhancing intratumoral accumulation. After entering tumor cells, there is excessive HO accumulation through the catalytic effect of overexpressed pyranose oxidase (PO) from microbial nanocomposite. This increases oxidative stress levels and triggers tumor autophagy. The autophagy-induced autophagosomes further promote Ads replication in infected tumor cells, leading to Ads-overactivated autophagy. Moreover, OMVs are powerful immunostimulants for remolding the immunosuppressive tumor microenvironment, facilitating antitumor immune response in preclinical cancer models in female mice. Therefore, the present autophagy-cascade-boosted immunotherapeutic method can expand OVs-based immunotherapy.
Topics: Female; Animals; Mice; Oncolytic Virotherapy; Adenoviridae; Bacterial Outer Membrane; Hydrogen Peroxide; Neoplasms; Autophagy; Oncolytic Viruses; Tumor Microenvironment
PubMed: 37217527
DOI: 10.1038/s41467-023-38679-z -
Cancer Letters Nov 2023Pancreatic cancer remains one of the deadliest cancers with extremely high mortality rate, and the number of cases is expected to steadily increase with time. Pancreatic... (Review)
Review
Pancreatic cancer remains one of the deadliest cancers with extremely high mortality rate, and the number of cases is expected to steadily increase with time. Pancreatic cancer is refractory to conventional cancer treatment options, like chemotherapy and radiotherapy, and commercialized immunotherapeutics, owing to its immunosuppressive and desmoplastic phenotype. Due to these reasons, development of an innovative treatment option that can overcome these challenges posed by the pancreatic tumor microenvironment (TME) is in an urgent need. The present review aims to summarize the evolution of oncolytic adenovirus (oAd) engineering and usage as therapeutics (either monotherapy or combination therapy) over the last decade to overcome these hurdles to instigate a potent antitumor effect against desmoplastic and immunosuppressive pancreatic cancer.
Topics: Humans; Oncolytic Virotherapy; Oncolytic Viruses; Adenoviridae; Pancreatic Neoplasms; Cell Line, Tumor; Tumor Microenvironment
PubMed: 37940067
DOI: 10.1016/j.canlet.2023.216456 -
Journal For Immunotherapy of Cancer Feb 2021The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving... (Review)
Review
The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving approval for some indications. Recently, OVs have also gathered interest as candidates to use in combination with immunotherapies for cancer due to their immunogenic properties, which include immunogenic cell death and the possibility to carry therapeutic transgenes in their genomes. OVs transform non-immunogenic 'cold' tumors into inflamed immunogenic 'hot' tumors, where immunotherapies show the highest efficacy. However, in monotherapy or in combination with immunotherapy, OVs face numerous challenges that limit their successful application, in particular upon systemic administration, such as liver sequestration, neutralizing interactions in blood, physical barriers to infection, and fast clearance by the immune system. In this regard, the use of mesenchymal stem cells (MSCs) as cells carrier for OV delivery addresses many of these obstacles acting as virus carriers and factories, expressing additional transgenes, and modulating the immune system. Here, I review the current progress of OVs-loaded MSCs in cancer, focusing on their interaction with the immune system, and discuss new strategies to improve their therapeutic efficacy.
Topics: Humans; Immunotherapy; Mesenchymal Stem Cells; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Tumor Microenvironment
PubMed: 33558278
DOI: 10.1136/jitc-2020-001684 -
Cytokine & Growth Factor Reviews Dec 2020Oncolytic virus immunotherapy is rapidly gaining interest in the field of immunotherapy against cancer. The minimal toxicity upon treatment and the dual activity of... (Review)
Review
Oncolytic virus immunotherapy is rapidly gaining interest in the field of immunotherapy against cancer. The minimal toxicity upon treatment and the dual activity of direct oncolysis and immune activation make therapy with oncolytic viruses (OVs) an interesting treatment modality. The safety and efficacy of several OVs have been assessed in clinical trials and, so far, the Food and Drug Administration (FDA) has approved one OV. Unfortunately, most treatments with OVs have shown suboptimal responses in clinical trials, while they appeared more promising in preclinical studies, with tumours reducing after immune cell influx. In several clinical trials with OVs, parameters such as virus replication, virus-specific antibodies, systemic immune responses, immune cell influx into tumours and tumour-specific antibodies have been studied as predictors or correlates of therapy efficacy. In this review, these studies are summarized to improve our understanding of the determinants of the efficacy of OV therapies in humans and to provide insights for future developments in the viro-immunotherapy treatment field.
Topics: Humans; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Virus Replication
PubMed: 32919831
DOI: 10.1016/j.cytogfr.2020.07.001 -
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 -
Gene Therapy Apr 2022Glioblastoma (GBM) is regarded as an incurable disease due to its poor prognosis and limited treatment options. Virotherapies were once utilized on cancers for their... (Review)
Review
Glioblastoma (GBM) is regarded as an incurable disease due to its poor prognosis and limited treatment options. Virotherapies were once utilized on cancers for their oncolytic effects. And they are being revived on GBM treatment, as accumulating evidence presents the immunogenic effects of virotherapies in remodeling immunosuppressive GBM microenvironment. In this review, we focus on the immune responses induced by oncolytic virotherapies and viral vectors in GBM. The current developments of GBM virotherapies are briefly summarized, followed by a detailed depiction of their immune response. Limitations and lessons inferred from earlier experiments and trials are discussed. Moreover, we highlight the importance of engaging the immune responses induced by virotherapies into the multidisciplinary management of GBM.
Topics: Brain Neoplasms; Glioblastoma; Humans; Oncolytic Virotherapy; Oncolytic Viruses; Tumor Microenvironment
PubMed: 33191399
DOI: 10.1038/s41434-020-00207-9 -
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