scholarly journals New Immunotherapeutic Approaches for Glioblastoma

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Gustavo Ignacio Vázquez Cervantes ◽  
Dinora F. González Esquivel ◽  
Saúl Gómez-Manzo ◽  
Benjamín Pineda ◽  
Verónica Pérez de la Cruz
Keyword(s):  
Clinical Trials ◽  
Immune Responses ◽  
Multimodal Treatment ◽  
Checkpoint Inhibitors ◽  
Current Treatment ◽  
Oncolytic Viruses ◽  
Median Survival Rate ◽  
Tumor Eradication ◽  
New Strategies ◽  
Primary Malignant Brain Tumor

Glioblastoma (GBM) is the most common primary malignant brain tumor with a high mortality rate. The current treatment consists of surgical resection, radiation, and chemotherapy; however, the median survival rate is only 12–18 months despite these alternatives, highlighting the urgent need to find new strategies. The heterogeneity of GBM makes this tumor difficult to treat, and the immunotherapies result in an attractive approach to modulate the antitumoral immune responses favoring the tumor eradication. The immunotherapies for GMB including monoclonal antibodies, checkpoint inhibitors, vaccines, and oncolytic viruses, among others, have shown favorable results alone or as a multimodal treatment. In this review, we summarize and discuss promising immunotherapies for GBM currently under preclinical investigation as well as in clinical trials.

Employing RNA viruses to fight cancer: novel insights into oncolytic virotherapy

2017 ◽  
Vol 398 (8) ◽  
pp. 891-909 ◽  
Author(s):  
Dörthe Masemann ◽  
Yvonne Boergeling ◽  
Stephan Ludwig
Keyword(s):  
Clinical Trials ◽  
Immune Responses ◽  
Tumor Targeting ◽  
Rna Viruses ◽  
Current Knowledge ◽  
Oncolytic Viruses ◽  
Cancer Therapies ◽  
Dna Viruses ◽  
Naturally Occurring ◽  
New Strategies

Abstract Within recent decades, viruses that specifically target tumor cells have emerged as novel therapeutic agents against cancer. These viruses do not only act via their cell-lytic properties, but also harbor immunostimulatory features to re-direct the tumor microenvironment and stimulate tumor-directed immune responses. Furthermore, oncolytic viruses are considered to be superior to classical cancer therapies due to higher selectivity towards tumor cell destruction and, consequently, less collateral damage of non-transformed healthy tissue. In particular, the field of oncolytic RNA viruses is rapidly developing since these agents possess alternative tumor-targeting strategies compared to established oncolytic DNA viruses. Thus, oncolytic RNA viruses have broadened the field of virotherapy facilitating new strategies to fight cancer. In addition to several naturally occurring oncolytic viruses, genetically modified RNA viruses that are armed to express foreign factors such as immunostimulatory molecules have been successfully tested in early clinical trials showing promising efficacy. This review aims to provide an overview of the most promising RNA viruses in clinical development, to summarize the current knowledge of clinical trials using these viral agents, and to discuss the main issues as well as future perspectives of clinical approaches using oncolytic RNA viruses.

scholarly journals Oncolytic Viruses for Malignant Glioma: On the Verge of Success?

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1294
Author(s):  
Yogesh R. Suryawanshi ◽  
Autumn J. Schulze
Keyword(s):  
Immune Responses ◽  
Malignant Glioma ◽  
Blood Brain Barrier ◽  
Tumor Heterogeneity ◽  
Checkpoint Inhibitors ◽  
Oncolytic Viruses ◽  
Brain Barrier ◽  
Current Status ◽  
Blood Brain ◽  
Federal Authority

Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking and chemo- and radiotherapy. Immunotherapeutic agents like oncolytic viruses, immune checkpoint inhibitors, and chimeric antigen receptor T cells have revolutionized cancer therapy, but their success in glioblastoma remains limited and further optimization of immunotherapies is needed. Several oncolytic viruses have demonstrated the ability to infect tumors and trigger anti-tumor immune responses in malignant glioma patients. Leading the pack, oncolytic herpesvirus, first in its class, awaits an approval for treating malignant glioma from MHLW, the federal authority of Japan. Nevertheless, some major hurdles like the blood–brain barrier, the immunosuppressive tumor microenvironment, and tumor heterogeneity can engender suboptimal efficacy in malignant glioma. In this review, we discuss the current status of malignant glioma therapies with a focus on oncolytic viruses in clinical trials. Furthermore, we discuss the obstacles faced by oncolytic viruses in malignant glioma patients and strategies that are being used to overcome these limitations to (1) optimize delivery of oncolytic viruses beyond the blood–brain barrier; (2) trigger inflammatory immune responses in and around tumors; and (3) use multimodal therapies in combination to tackle tumor heterogeneity, with an end goal of optimizing the therapeutic outcome of oncolytic virotherapy.

scholarly journals Mesenchymal stem cells and oncolytic viruses: joining forces against cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001684
Author(s):  
Rafael Moreno
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Immune System ◽  
Oncolytic Viruses ◽  
Immunogenic Cell Death ◽  
The Past ◽  
Physical Barriers ◽  
Immunogenic Properties ◽  
New Strategies

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.

scholarly journals Clinical landscape of oncolytic virus research in 2020

2020 ◽  
Vol 8 (2) ◽  
pp. e001486 ◽  
Author(s):  
Nicholas Macedo ◽  
David M Miller ◽  
Rizwan Haq ◽  
Howard L Kaufman
Keyword(s):  
Clinical Trials ◽  
Immune Responses ◽  
Plaque Assay ◽  
Cancer Therapeutics ◽  
Oncolytic Viruses ◽  
Low Grade ◽  
Current Profile ◽  
Tumor Biopsy ◽  
The Impact ◽  
Insight Into

Oncolytic viruses (OVs) are a new class of cancer therapeutics. This review was undertaken to provide insight into the current landscape of OV clinical trials. A PubMed search identified 119 papers from 2000 to 2020 with 97 studies reporting data on 3233 patients. The viruses used, presence of genetic modifications and/or transgene expression, cancer types targeted, inclusion of combination strategies and safety profile were reported. In addition, information on viral bioshedding across the studies, including which tissues or body fluids were evaluated and how virus was detected (eg, PCR, plaque assay or both), is also reported. Finally, the number of studies evaluating antiviral and antitumor humoral and cellular immune responses were noted. We found that adenovirus (n=30) is the most common OV in clinical trials with approximately two-thirds (n=63) using modified or recombinant viral backbones and granulocyte-macrophage colony-stimulating factor (n=24) was the most common transgene. The most common tumors targeted were melanoma (n=1000) and gastrointestinal (GI; n=577) cancers with most using monotherapy OVs given by intratumoral (n=1482) or intravenous (n=1347) delivery. The most common combination included chemotherapy (n=36). Overall, OV treatment-related adverse events were low-grade constitutional and local injection site reactions. Viral shedding was frequently measured although many studies restricted this to blood and tumor tissue and used PCR only. While most studies did report antiviral antibody titers (n=63), only a minority of studies reported viral-specific T cell responses (n=10). Tumor immunity was reported in 48 studies and largely relied on general measures of immune activation (eg, tumor biopsy immunohistochemistry (n=25) and serum cytokine measurement (n=19)) with few evaluating tumor-specific immune responses (n=7). Objective responses were reported in 292 (9%) patients and disease control was achieved in 681 (21.1%) patients, although standard reporting criteria were only used in 53% of the trials. Completed clinical trials not reported in the peer-reviewed literature were not included in this review potentially underestimating the impact of OV treatment. These data provide insight into the current profile of OV clinical trials reporting and identifies potential gaps where further studies are needed to better define the role of OVs, alone and in combination, for patients with cancer.

scholarly journals Current strategies to circumvent the antiviral immunity to optimize cancer virotherapy

2021 ◽  
Vol 9 (4) ◽  
pp. e002086
Author(s):  
Dong Ho Shin ◽  
Teresa Nguyen ◽  
Bulent Ozpolat ◽  
Frederick Lang ◽  
Marta Alonso ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Immune Responses ◽  
Treatment Modality ◽  
Antitumor Immunity ◽  
Antiviral Immunity ◽  
Clinical Impact ◽  
Oncolytic Viruses ◽  
Paradigm Shifting

Cancer virotherapy is a paradigm-shifting treatment modality based on virus-mediated oncolysis and subsequent antitumor immune responses. Clinical trials of currently available virotherapies showed that robust antitumor immunity characterizes the remarkable and long-term responses observed in a subset of patients. These data suggest that future therapies should incorporate strategies to maximize the immunotherapeutic potential of oncolytic viruses. In this review, we highlight the recent evidence that the antiviral immunity of the patients may limit the immunotherapeutic potential of oncolytic viruses and summarize the most relevant approaches to strategically redirect the immune response away from the viruses and toward tumors to heighten the clinical impact of viro-immunotherapy platforms.

scholarly journals Oncolytic Viruses: Newest Frontier for Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5452
Author(s):  
Masmudur M. Rahman ◽  
Grant McFadden
Keyword(s):  
Clinical Trials ◽  
Immune Responses ◽  
Cancer Patient ◽  
Cancer Cells ◽  
Treatment Modality ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Therapeutic Approaches ◽  
Cancer Treatments ◽  
The Past

Cancer remains a leading cause of death worldwide. Despite many signs of progress, currently available cancer treatments often do not provide desired outcomes for too many cancers. Therefore, newer and more effective therapeutic approaches are needed. Oncolytic viruses (OVs) have emerged as a novel cancer treatment modality, which selectively targets and kills cancer cells while sparing normal ones. In the past several decades, many different OV candidates have been developed and tested in both laboratory settings as well as in cancer patient clinical trials. Many approaches have been taken to overcome the limitations of OVs, including engineering OVs to selectively activate anti-tumor immune responses. However, newer approaches like the combination of OVs with current immunotherapies to convert “immune-cold” tumors to “immune-hot” will almost certainly improve the potency of OVs. Here, we discuss strategies that are explored to further improve oncolytic virotherapy.

scholarly journals Activation of viral defense signaling in cancer

2018 ◽  
Vol 10 ◽  
pp. 175883591879310 ◽  
Author(s):  
Maria Gonzalez-Cao ◽  
Niki Karachaliou ◽  
Mariacarmela Santarpia ◽  
Santiago Viteri ◽  
Andreas Meyerhans ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Immune Responses ◽  
Immune Checkpoint Inhibitors ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Cancer Therapies ◽  
Microbial Infection ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

A coordinated action of innate and adaptive immune responses is required to efficiently combat a microbial infection. It has now become clear that cancer therapies also largely benefit when both arms of the immune response are engaged. In this review, we will briefly describe the current knowledge of innate immunity and how this can be utilized to prime tumors for a better response to immune checkpoint inhibitors. Comments on compounds in development and ongoing clinical trials will be provided.

scholarly journals The State of Immunotherapy in Hepatobiliary Cancers

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2096
Author(s):  
Farhan Z. Ilyas ◽  
Joal D. Beane ◽  
Timothy M. Pawlik
Keyword(s):  
Clinical Trials ◽  
Adoptive Transfer ◽  
Immune Checkpoint ◽  
Therapeutic Approach ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Oncolytic Viruses ◽  
Curative Intent ◽  
Important Approach

Hepatobiliary cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and gallbladder carcinoma (GBC), are lethal cancers with limited therapeutic options. Curative-intent treatment typically involves surgery, yet recurrence is common and many patients present with advanced disease not amenable to an operation. Immunotherapy represents a promising approach to improve outcomes, but the immunosuppressive tumor microenvironment of the liver characteristic of hepatobiliary cancers has hampered the development and implementation of this therapeutic approach. Current immunotherapies under investigation include immune checkpoint inhibitors (ICI), the adoptive transfer of immune cells, bispecific antibodies, vaccines, and oncolytic viruses. Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two ICIs that have demonstrated utility in HCC, and newer immune checkpoint targets are being tested in clinical trials. In advanced CCA and GBC, PD-1 ICIs have resulted in antitumor responses, but only in a minority of select patients. Other ICIs are being investigated for patients with CCA and GBC. Adoptive transfer may hold promise, with reports of complete durable regression in metastatic CCA, yet this therapeutic approach may not be generalizable. Alternative approaches have been developed and promising results have been observed, but clinical trials are needed to validate their utility. While the treatment of hepatobiliary cancers involves unique challenges that these cancers present, the progress seen with ICIs and adoptive transfer has solidified immunotherapy as an important approach in these challenging patients with few other effective treatment options.

scholarly journals Oncolytic Viruses and Immune Checkpoint Inhibitors: Preclinical Developments to Clinical Trials

2020 ◽  
Vol 21 (22) ◽  
pp. 8627 ◽  
Author(s):  
June Kyu Hwang ◽  
JinWoo Hong ◽  
Chae-Ok Yun
Keyword(s):  
Clinical Trials ◽  
Immune Checkpoint ◽  
Therapeutic Potential ◽  
Checkpoint Inhibitors ◽  
Immune Surveillance ◽  
Oncolytic Viruses ◽  
Small Subset ◽  
Tumor Microenvironments ◽  
Oncology Research ◽  
Treatment Paradigm

Immuno-oncology (IO) has been an active area of oncology research. Following US FDA approval of the first immune checkpoint inhibitor (ICI), ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody), in 2011, and of the first oncolytic virus, Imlygic (talimogene laherparepvec), in 2015, there has been renewed interest in IO. In the past decade, ICIs have changed the treatment paradigm for many cancers by enabling better therapeutic control, resuming immune surveillance, suppressing tumor immunosuppression, and restoring antitumor immune function. However, ICI therapies are effective only in a small subset of patients and show limited therapeutic potential due to their inability to demonstrate efficacy in ‘cold’ or unresponsive tumor microenvironments (TMEs). Relatedly, oncolytic viruses (OVs) have been shown to induce antitumor immune responses, augment the efficacy of existing cancer treatments, and reform unresponsive TME to turn ‘cold’ tumors ‘hot,’ increasing their susceptibility to checkpoint blockade immunotherapies. For this reason, OVs serve as ideal complements to ICIs, and multiple preclinical studies and clinical trials are demonstrating their combined therapeutic efficacy. This review will discuss the merits and limitations of OVs and ICIs as monotherapy then progress onto the preclinical rationale and the results of clinical trials of key combination therapies.

Sign in / Sign up

Export Citation Format

Share Document