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International Journal of Molecular... Oct 2023Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients... (Review)
Review
Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients remains poor. Immunotherapy has recently emerged as a potential treatment option. The aim of this systematic review is to assess the current strategies and future perspectives of the GBM immunotherapy strategies. A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 3 September 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "glioblastomas," "immunotherapies," and "treatment." The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of immunotherapies for the treatment of gliomas in human subjects. A total of 1588 papers are initially identified. Eligibility is confirmed for 752 articles, while 655 are excluded for various reasons, including irrelevance to the research topic (627), insufficient method and results details (12), and being case-series or cohort studies (22), systematic literature reviews, or meta-analyses (3). All the studies within the systematic review were clinical trials spanning from 1995 to 2023, involving 6383 patients. Neuro-oncology published the most glioma immunotherapy-related clinical trials (15/97, 16%). Most studies were released between 2018 and 2022, averaging nine publications annually during this period. Adoptive cellular transfer chimeric antigen receptor (CAR) T cells were the primary focus in 11% of the studies, with immune checkpoint inhibitors (ICIs), oncolytic viruses (OVs), and cancer vaccines (CVs) comprising 26%, 12%, and 51%, respectively. Phase-I trials constituted the majority at 51%, while phase-III trials were only 7% of the total. Among these trials, 60% were single arm, 39% double arm, and one multi-arm. Immunotherapies were predominantly employed for recurrent GBM (55%). The review also revealed ongoing clinical trials, including 9 on ICIs, 7 on CVs, 10 on OVs, and 8 on CAR T cells, totaling 34 trials, with phase-I trials representing the majority at 53%, and only one in phase III. Overcoming immunotolerance, stimulating robust tumor antigen responses, and countering immunosuppressive microenvironment mechanisms are critical for curative GBM immunotherapy. Immune checkpoint inhibitors, such as PD-1 and CTLA-4 inhibitors, show promise, with the ongoing research aiming to enhance their effectiveness. Personalized cancer vaccines, especially targeting neoantigens, offer substantial potential. Oncolytic viruses exhibited dual mechanisms and a breakthrough status in the clinical trials. CAR T-cell therapy, engineered for specific antigen targeting, yields encouraging results, particularly against IL13 Rα2 and EGFRvIII. The development of second-generation CAR T cells with improved specificity exemplifies their adaptability.
Topics: Humans; Glioblastoma; Immune Checkpoint Inhibitors; Cancer Vaccines; Neoplasm Recurrence, Local; Glioma; Immunotherapy; Immunotherapy, Adoptive; Brain Neoplasms; Tumor Microenvironment
PubMed: 37894718
DOI: 10.3390/ijms242015037 -
Cancers May 2020Oncolytic virotherapy is a promising antitumor therapeutic strategy. It is based on the ability of viruses to selectively kill cancer cells and induce host antitumor... (Review)
Review
Oncolytic virotherapy is a promising antitumor therapeutic strategy. It is based on the ability of viruses to selectively kill cancer cells and induce host antitumor immune responses. However, the clinical outcomes of oncolytic viruses (OVs) vary widely. Therefore, we performed a meta-analysis to illustrate the efficacy and safety of oncolytic viruses. The Cochrane Library, PubMed, and EMBASE databases were searched for randomized controlled trials (RCTs) published up to January 31, 2020. The data for objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were independently extracted by two investigators from 11 studies that met the inclusion criteria. In subgroup analyses, the objective response rate benefit was observed in patients treated with oncolytic DNA viruses (odds ratio (OR) = 4.05; 95% confidence interval (CI): 1.96-8.33; = 0.0002), but not in those treated with oncolytic RNA viruses (OR = 1.00, 95% CI: 0.66-1.52, = 0.99). Moreover, the intratumoral injection arm yielded a statistically significant improvement (OR = 4.05, 95% CI: 1.96-8.33, = 0.0002), but no such improvement was observed for the intravenous injection arm (OR = 1.00, 95% CI: 0.66-1.52, = 0.99). Among the five OVs investigated in RCTs, only talimogene laherparepvec (T-VEC) effectively prolonged the OS of patients (hazard ratio (HR), 0.79; 95% CI: 0.63-0.99; = 0.04). None of the oncolytic virotherapies improved the PFS (HR = 1.00, 95% CI: 0.85-1.19, = 0.96). Notably, the pooled rate of severe AEs (grade ≥3) was higher for the oncolytic virotherapy group (39%) compared with the control group (27%) (risk difference (RD), 12%; risk ratio (RR), 1.44; 95% CI: 1.17-1.78; = 0.0006). This review offers a reference for fundamental research and clinical treatment of oncolytic viruses. Further randomized controlled trials are needed to verify these results.
PubMed: 32486227
DOI: 10.3390/cancers12061416 -
International Journal of Molecular... Oct 2020Leveraging the immune system to thwart cancer is not a novel strategy and has been explored via cancer vaccines and use of immunomodulators like interferons. However, it... (Meta-Analysis)
Meta-Analysis
Leveraging the immune system to thwart cancer is not a novel strategy and has been explored via cancer vaccines and use of immunomodulators like interferons. However, it was not until the introduction of immune checkpoint inhibitors that we realized the true potential of immunotherapy in combating cancer. Oncolytic viruses are one such immunotherapeutic tool that is currently being explored in cancer therapeutics. We present the most comprehensive systematic review of all oncolytic viruses in Phase 1, 2, and 3 clinical trials published to date. We performed a systematic review of all published clinical trials indexed in PubMed that utilized oncolytic viruses. Trials were reviewed for type of oncolytic virus used, method of administration, study design, disease type, primary outcome, and relevant adverse effects. A total of 120 trials were found; 86 trials were available for our review. Included were 60 phase I trials, five phase I/II combination trials, 19 phase II trials, and two phase III clinical trials. Oncolytic viruses are feverously being evaluated in oncology with over 30 different types of oncolytic viruses being explored either as a single agent or in combination with other antitumor agents. To date, only one oncolytic virus therapy has received an FDA approval but advances in bioengineering techniques and our understanding of immunomodulation to heighten oncolytic virus replication and improve tumor kill raises optimism for its future drug development.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Gene Transfer Techniques; Genetic Vectors; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Treatment Outcome
PubMed: 33053757
DOI: 10.3390/ijms21207505 -
Translational Cancer Research Oct 2021Cancer treatment remains one of the most formidable challenges worldwide. Some novel treatment strategies, including molecularly targeted therapy, gene therapy, and...
BACKGROUND
Cancer treatment remains one of the most formidable challenges worldwide. Some novel treatment strategies, including molecularly targeted therapy, gene therapy, and cellular immunotherapy, have also been investigated to improve therapeutic effects for cancer patients and have demonstrated unexpected positive effects. This systematic review and meta-analysis evaluated the efficacy and safety of oncolytic virus (OV) monotherapy or combination therapy for intermediate to advanced solid tumors.
METHODS
We retrieved articles from PubMed, Embase, Web of Science, CNKI, Wanfang and VIP. The quality of the included studies was assessed by Review Manager Software version 5.3. STATA software was used to perform meta-analyses of efficacy, overall survival (OS) and adverse reactions.
RESULTS
A total of 22 studies involving 3,996 patients were included in this analysis, including 13 H101 studies, 5 T-VEC studies, 2 Pexa-Vec studies, 1 HF10 study and 1 Reolysin study. Regarding oncolytic adenovirus H101, meta-analysis showed that patients treated with H101 monotherapy or H101 combined with chemotherapy had a significantly higher objective response rate (ORR) than those treated with chemotherapy. Patients in the H101 and T-VEC groups had significantly longer effect size (ES) than the control group patients. The odds ratio (OR) and ES of patients with hepatocellular carcinoma, lung cancer and melanoma treated with OV were analyzed. For the safety profile, the total incidence of adverse reactions was similar in both groups. In terms of the other OVs, according to a systematic review, we found that after Reolysin treatment, the ORR was 26.9% in patients with head and neck cancer. The phase I study of HF10 exhibited some therapeutic potential. The adverse events (AEs) associated with the other OVs mainly included fever, nausea and vomiting, leukopenia, and hypotension.
DISCUSSION
OVs are effective and well tolerated for the treatment of intermediate to advanced solid cancer and represent a promising therapeutic approach for solid cancers.
PubMed: 35116288
DOI: 10.21037/tcr-21-905 -
Virology Journal Nov 2023The efficacy and safety of oncolytic virotherapies in the treatment of advanced melanoma still remains controversal. It is necessary to conduct quantitative evaluation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy and safety of oncolytic virotherapies in the treatment of advanced melanoma still remains controversal. It is necessary to conduct quantitative evaluation on the basis of preclinical trial reports.
METHODS
Publicly available databases (PubMed, Embase, Medline, Web of Science and Cochrane Library.) and register (Clinicaltrials.gov) were searched to collect treatment outcomes of oncolytic virotherapies (including herpes simplex virus type 1 (HSV), coxsackievirus A21 (CVA21), adenovirus, poxvirus and reovirus) for advanced/unresectable melanoma. Comparisons of treatment response, adverse events (AEs) and survival analyses for different virotherapies were performed by R software based on the extracted data from eligible studies.
RESULTS
Finally, thirty-four eligible studies were analysed and HSV virotherapy had the highest average complete response (CR, 24.8%) and HSV had a slightly higher average overall response rate (ORR) than CVA21 (43.8% vs 42.6%). In the pooled results of comparing talimogene laherparepve (T-VEC) with or without GM-CSF/ICIs (immune checkpoint inhibitors) to GM-CSF/ICIs monotherapy suggested virotherapy was more efficient in subgroups CR (RR = 1.80, 95% CI [1.30; 2.51], P < 0.01), ORR (RR = 1.17, 95% CI [1.02; 1.34], P < 0.05), and DCR (RR = 1.27, 95% CI [1.15; 1.40], P < 0.01). In patients treated with T-VEC+ICIs, 2-year overall survival (12.1 ± 6.9 months) and progression-free survival (9.9 ± 6.9) were significantly longer than those treated with T-VEC alone. Furthermore, we found that AEs occurred frequently in virotherapy but decreased in a large cohort of enrolled patients, some of which, such as abdominal distension/pain, injection site pain and pruritus, were found to be positively associated with disease progression in patients treated with T-VEC monotherapy.
CONCLUSION
Given the relative safety and tolerability of oncolytic viruses, and the lack of reports of dose-limiting-dependent toxicities, more patients treated with T-VEC with or without ICIs should be added to future assessment analyses. There is still a long way to go before it can be used as a first-line therapy for patients with advanced or unresectable melanoma.
Topics: Humans; Oncolytic Virotherapy; Granulocyte-Macrophage Colony-Stimulating Factor; Immunotherapy; Melanoma; Oncolytic Viruses; Pain
PubMed: 37919738
DOI: 10.1186/s12985-023-02220-x -
Vaccines Sep 2022Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Current therapies often provide marginal survival benefits at the... (Review)
Review
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Current therapies often provide marginal survival benefits at the expense of undesirable side effects. Oncolytic viruses represent a novel strategy for the treatment of HCC due to their inherent ability to cause direct tumor cell lysis while sparing normal tissue and their capacity to stimulate potent immune responses directed against uninfected tumor cells and distant metastases. Oncolytic virotherapy (OVT) is a promising cancer treatment, but before it can become a standard option in practice, several challenges-systemic viral delivery optimization/enhancement, inter-tumoral virus dispersion, anti-cancer immunity cross-priming, and lack of artificial model systems-need to be addressed. Addressing these will require an in vivo model that accurately mimics the tumor microenvironment and allows the scientific community to design a more precise and accurate OVT. Due to their close physiologic resemblance to humans, murine cancer models are the likely preferred candidates. To provide an accurate assessment of the current state of in vivo OVT in HCC, we have reviewed a comprehensively searched body of work using murine in vivo HCC models for OVT.
PubMed: 36146619
DOI: 10.3390/vaccines10091541 -
Discover Oncology Oct 2023In the past decade, there has been little progress in the treatment of malignant glioma. Recently, oncolytic virus has made great progress in glioma treatment, and a... (Review)
Review
PURPOSE
In the past decade, there has been little progress in the treatment of malignant glioma. Recently, oncolytic virus has made great progress in glioma treatment, and a number of clinical trials have shown their potential of prolonging the survival time of glioma patients. Our objective is to evaluate effectiveness and safety of oncolytic virus (OV) in malignant glioma treatment.
METHODOLOGY
Based upon PRISMA, we collected relevant published clinical trials by searching medical databases up to January 16, 2023, applying the language restrictions in English and Chinese. We cross-searched the terms: 'glioma', 'glioblastoma', 'oncolytic viruses', 'oncolytic virotherapy' with filter 'clinical trial'. Two researchers independently extracted the data regarding case definitions, published years, trial phase, characteristics of patients, administration of drug, overall survival (OS), and adverse events.
RESULTS
19 published clinical trials in OV treatment of malignant glioma were included in the further systematic review analysis. None of them induced irresistible adverse effects attributing to OV treatment, median overall survival varied from 3.25 to 20.2 months after treatments. According to trials providing patient's detailed molecular diagnosis, we find that the effectiveness of OV treatment has no significant difference in patients with different IDH or MGMT status.
CONCLUSIONS
Current clinical trials have initially shown the potential of oncolytic virotherapy as a new treatment for malignant glioma. Besides development of virus types, the strategy of OV use is an urgent problem to be solved in future clinical application, such as repeated administrations, innovative drug delivery systems, and biomarkers.
PubMed: 37845388
DOI: 10.1007/s12672-023-00769-1 -
Virology Journal May 2021In recent years, oncolytic viruses (OVs) have drawn attention as a novel therapy to various types of cancers, both in clinical and preclinical cancer studies all around... (Review)
Review
BACKGROUND
In recent years, oncolytic viruses (OVs) have drawn attention as a novel therapy to various types of cancers, both in clinical and preclinical cancer studies all around the world. Consequently, researchers have been actively working on enhancing cancer therapy since the early twentieth century. This study presents a systematic review of the literature on OVs, discusses underlying research clusters and, presents future directions of OVs research.
METHODS
A total of 1626 published articles related to OVs as cancer therapy were obtained from the Web of Science (WoS) database published between January 2000 and March 2020. Various aspects of OVs research, including the countries/territories, institutions, journals, authors, citations, research areas, and content analysis to find trending and emerging topics, were analysed using the bibliometrix package in the R-software.
RESULTS
In terms of the number of publications, the USA based researchers were the most productive (n = 611) followed by Chinese (n = 197), and Canadian (n = 153) researchers. The Molecular Therapy journal ranked first both in terms of the number of publications (n = 133) and local citations (n = 1384). The most prominent institution was Mayo Clinic from the USA (n = 117) followed by the University of Ottawa from Canada (n = 72), and the University of Helsinki from Finland (n = 63). The most impactful author was Bell J.C with the highest number of articles (n = 67) and total local citations (n = 885). The most impactful article was published in the Cell journal. In addition, the latest OVs research mainly builds on four research clusters.
CONCLUSION
The domain of OVs research has increased at a rapid rate from 2000 to 2020. Based on the synthesis of reviewed studies, adenovirus, herpes simplex virus, reovirus, and Newcastle disease virus have shown potent anti-cancer activity. Developed countries such as the USA, Canada, the UK, and Finland were the most productive, hence, contributed most to this field. Further collaboration will help improve the clinical research translation of this therapy and bring benefits to cancer patients worldwide.
Topics: Bibliometrics; Databases, Factual; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 33980264
DOI: 10.1186/s12985-021-01571-7 -
Future Science OA Aug 2021Thyroid cancer incidence and related mortality is increasing year-on-year, and although treatment for early disease with surgery and radioiodine results in a 98% 5-year... (Review)
Review
Thyroid cancer incidence and related mortality is increasing year-on-year, and although treatment for early disease with surgery and radioiodine results in a 98% 5-year survival rate, recurrence and treatment refractory disease is evident in an unacceptable number of patients. Alternative treatment regimens have therefore been sought in the form of tyrosine kinase inhibitors, immunotherapy, vaccines, chimeric antigen receptor T-cell therapy and oncolytic viruses. The current review aims to consolidate knowledge and highlight the latest clinical trials using secondary therapies in thyroid cancer treatment, focusing on both and studies, which have investigated therapies other than radioiodine.
PubMed: 34258030
DOI: 10.2144/fsoa-2021-0041 -
Frontiers in Immunology 2023Cancer incidence and mortality are increasing rapidly worldwide, necessitating further investigation into developing and optimizing emergent cancer therapies. Oncolytic...
BACKGROUND
Cancer incidence and mortality are increasing rapidly worldwide, necessitating further investigation into developing and optimizing emergent cancer therapies. Oncolytic viruses such as vesicular stomatitis virus encoding interferon β (VSV-IFNβ) have attracted considerable attention, as they offer great efficacy and safety profiles. This systematic review aimed to determine and compare the efficacy profile between VSV-IFNβ and non-treatment controls in preclinical cancer models.
METHODOLOGY
The Embase and Medline databases were systematically searched for relevant studies using related key terms and Medical Subject Headings (MeSH). Titles, abstracts, and full texts were screened, and data from eligible articles were extracted by two groups independently and in duplicate (two reviewers per group). Disagreements were resolved by a fifth independent reviewer. The included articles were all preclinical (translational) English studies that investigated and compared the efficacy profile between VSV-IFNβ and non-treatment controls in animal models. The risk of bias among the studies was assessed by two reviewers independently and in duplicate using SYRCLE's risk-of-bias tool for animal studies; disparities were addressed by a third independent reviewer.
RESULTS
After employing relevant MeSH and key terms, we identified 1598 articles. A total of 87 articles were either duplicates or conference proceedings and were thus excluded. Following title and abstract screening, 37 articles were included in the full-text assessment. Finally, 14 studies met the eligibility criteria. Forty-two experiments from the included studies examined the potential efficacy of VSV-IFNβ through different routes of administration, including intratumoral, intraperitoneal, and intravenous routes. Thirty-seven experiments reported positive outcomes. Meanwhile, five experiments reported negative outcomes, three and two of which examined intratumoral and intravenous VSV-IFNβ administration, respectively.
CONCLUSION
Although the majority of the included studies support the promising potential of VSV-IFNβ as an oncolytic virus, further research is necessary to ensure a safe and efficacious profile to translate its application into clinical trials.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022335418.
Topics: Animals; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Vesicular stomatitis Indiana virus; Vesiculovirus; Interferon-beta
PubMed: 37063914
DOI: 10.3389/fimmu.2023.1085940