The Experts below are selected from a list of 10782 Experts worldwide ranked by ideXlab platform
Howard L. Kaufman - One of the best experts on this subject based on the ideXlab platform.
-
Advancing Oncolytic Virus therapy by understanding the biology
Nature reviews. Clinical oncology, 2021Co-Authors: Howard L. Kaufman, Dawid MaciorowskiAbstract:Talimogene laherparepvec (T-VEC) is an Oncolytic Virus approved for the treatment of patients with recurrent melanoma. Now, a recent study in patients with primary cutaneous B cell lymphoma confirms prior results in melanoma and reveals new mechanisms of action. Herein, we discuss these findings and their implications for expanding the role of Oncolytic Viruses.
-
mek inhibition enhances Oncolytic Virus immunotherapy through increased tumor cell killing and t cell activation
Science Translational Medicine, 2018Co-Authors: Praveen K Bommareddy, Salvatore M Aspromonte, Andrew Zloza, Samuel D Rabkin, Howard L. KaufmanAbstract:Melanoma is an aggressive cutaneous malignancy, but advances over the past decade have resulted in multiple new therapeutic options, including molecularly targeted therapy, immunotherapy, and Oncolytic Virus therapy. Talimogene laherparepvec (T-VEC) is a herpes simplex type 1 Oncolytic Virus, and trametinib is a MEK inhibitor approved for treatment of melanoma. Therapeutic responses with T-VEC are often limited, and BRAF/MEK inhibition is complicated by drug resistance. We observed that the combination of T-VEC and trametinib resulted in enhanced melanoma cell death in vitro. Further, combination treatment resulted in delayed tumor growth and improved survival in mouse models. Tumor regression was dependent on activated CD8+ T cells and Batf3+ dendritic cells. We also observed antigen spreading and induction of an inflammatory gene signature, including increased expression of PD-L1. Triple therapy with the combination of T-VEC, MEK inhibition, and anti-PD-1 antibody further augmented responses. These data support clinical development of combination Oncolytic Viruses, MEK inhibitors, and checkpoint blockade in patients with melanoma.
-
durable response rate as an endpoint in cancer immunotherapy insights from Oncolytic Virus clinical trials
Journal for ImmunoTherapy of Cancer, 2017Co-Authors: Howard L. Kaufman, Robert H I Andtbacka, Frances A Collichio, Michael Wolf, Z Zhao, Mark Shilkrut, Igor Puzanov, Merrick I RossAbstract:Traditional response criteria may be insufficient to characterize full clinical benefits of anticancer immunotherapies. Consequently, endpoints such as durable response rate (DRR; a continuous response [complete or partial objective response] beginning within 12 months of treatment and lasting ≥6 months) have been employed. There has not, however, been validation that DRR correlates with other more traditional endpoints of clinical benefit such as overall survival. We evaluated whether DRR was associated with clinically meaningful measures of benefit (eg, overall survival [OS], quality of life [QoL], or treatment-free interval [TFI]) in a phase 3 clinical trial of an Oncolytic Virus for melanoma treatment. To evaluate the association between DRR and OS and to mitigate lead time bias, landmark analyses were used. QoL was evaluated using the FACT-BRM questionnaire (comprising the FACT-BRM Physical, Social/Family, Emotional, and Functional well-being domains, the Additional Concerns, Physical and Mental treatment-specific subscales, and the Trial Outcome Index [TOI]). TFI was defined as time from the last study therapy dose to first subsequent therapy dose (including any systemic anticancer therapy for melanoma after study therapy discontinuation). Four hundred thirty-six patients were included in the intent-to-treat population. Achieving DR was associated with a statistically significant improvement in OS in a landmark analysis at 9 months (HR = 0.07; P = 0.0003), 12 months (HR = 0.05, P < 0.0001), and 18 months (HR = 0.11; P = 0.0002) that persisted after adjusting for disease stage and line of therapy. Achieving a DR was associated with a longer median TFI (HR = 0.33; P = 0.0007) and a higher TOI improvement rate (58.1% versus 30.0%; P = 0.025). Achieving a DR was associated with clinical benefits such as improved OS and QoL and prolonged TFI, thus supporting the usefulness of DR as a meaningful immunotherapy clinical trial endpoint. ClinicalTrials.gov identifier, NCT00769704 ( https://clinicaltrials.gov/ct2/show/NCT00769704 ) October 7, 2008
-
Talimogene Laherparepvec (T-VEC) and Other Oncolytic Viruses for the Treatment of Melanoma
American Journal of Clinical Dermatology, 2017Co-Authors: Praveen K Bommareddy, Anand Patel, Saamia Hossain, Howard L. KaufmanAbstract:Many mammalian Viruses have properties that can be commandeered for the treatment of cancer. These characteristics include preferential infection and replication in tumor cells, the initiation of tumor cell lysis, and the induction of innate and adaptive anti-tumor immunity. Furthermore, Viruses can be genetically engineered to reduce pathogenicity and increase immunogenicity resulting in minimally toxic therapeutic agents. Talimogene laherparepvec (T-VEC; Imlygic™), is a genetically modified herpes simplex Virus, type 1, and is the first Oncolytic Virus therapy to be approved for the treatment of advanced melanoma by the US FDA. T-VEC is attenuated by the deletion of the herpes neurovirulence viral genes and enhanced for immunogenicity by the deletion of the viral ICP47 gene. Immunogenicity is further supported by expression of the human granulocyte–macrophage colony-stimulating factor (GM-CSF) gene, which helps promote the priming of T cell responses. T-VEC demonstrated significant improvement in durable response rate, objective response rate, and progression-free survival in a randomized phase III clinical trial for patients with advanced melanoma. This review will discuss the optimal selection of patients for such treatment and describe how therapy is optimally delivered. We will also discuss future directions for Oncolytic Virus immunotherapy, which will likely include combination T-VEC clinical trials, expansion of T-VEC to other types of non-melanoma skin cancers, and renewed efforts at Oncolytic Virus drug development with other Viruses.
-
molecular pathways mechanism of action for talimogene laherparepvec a new Oncolytic Virus immunotherapy
Clinical Cancer Research, 2016Co-Authors: Frederick J Kohlhapp, Howard L. KaufmanAbstract:Oncolytic Viruses are native or engineered Viruses that preferentially replicate in and lyse cancer cells. Selective tumor cell replication is thought to depend on infection of neoplastic cells, which harbor low levels of protein kinase R (PKR) and dysfunctional type I IFN signaling elements. These changes allow more efficient viral replication, and with selected deletion of specific viral genes, replication in normal cells with activated PKR may not be possible. Direct tumor cell lysis, release of soluble tumor antigens, and danger-associated molecular factors are all thought to help prime and promote tumor-specific immunity. Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex Virus, type I and is the first Oncolytic Virus to demonstrate a clinical benefit in patients with melanoma. T-VEC has also been evaluated for the treatment of head and neck cancer, pancreatic cancer, and likely other types of cancer will be targeted in the near future. T-VEC has been modified for improved safety, tumor-selective replication, and induction of host immunity by deletion of several viral genes and expression of human granulocyte-macrophage colony stimulating factor. Although the mechanism of action for T-VEC is incompletely understood, the safety profile of T-VEC and ability to promote immune responses suggest future combination studies with other immunotherapy approaches including checkpoint blockade through PD-1, PD-L1, and CTLA-4 to be a high priority for clinical development. Oncolytic Viruses also represent unique regulatory and biosafety challenges but offer a potential new class of agents for the treatment of cancer.
Douglas S. Lyles - One of the best experts on this subject based on the ideXlab platform.
-
Vesicular stomatitis Virus as a treatment for colorectal cancer
Cancer Gene Therapy, 2011Co-Authors: J H Stewart, S A Northrup, M Willingham, M. Ahmed, Douglas S. LylesAbstract:M protein mutant vesicular stomatitis Virus is an attractive candidate Oncolytic Virus for the treatment of metastatic colorectal cancer due to its ability to kill cancer cells that are defective in their antiviral responses. The Oncolytic activity of recombinant wild-type and M protein mutant vesicular stomatitis Viruses was determined in RKO, Hct116 and LoVo colorectal cancer cells, as well as in human fibroblast and hepatocyte primary cultures. RKO and Hct116 cells were sensitive to both Viruses, whereas LoVo cells were resistant. [^35S]methionine labeling experiments and viral plaque assays showed that sensitive and resistant colorectal cancer cells supported viral protein and progeny production after infection with either Virus. Colorectal cancer cells were pretreated with β -interferon and infected with vesicular stomatitis Virus to evaluate the extent to which interferon signaling is downregulated in colorectal cancer cells. Although colorectal cancer cells retained some degree of interferon signaling, this signaling did not negatively impact the Oncolytic effects of either Virus in sensitive cells. Murine xenografts of RKO cells were effectively treated by intratumoral injections with M protein mutant Virus, whereas LoVo xenografts were resistant to treatment with this Virus. These results suggest that M protein mutant vesicular stomatitis Virus is a good candidate Oncolytic Virus for the treatment of selected metastatic colorectal cancers.
-
Oncolytic vesicular stomatitis Virus induces apoptosis in u87 glioblastoma cells by a type ii death receptor mechanism and induces cell death and tumor clearance in vivo
Journal of Virology, 2011Co-Authors: Zachary D Cary, Mark C Willingham, Douglas S. LylesAbstract:Vesicular stomatitis Virus (VSV) is a potential Oncolytic Virus for treating glioblastoma multiforme (GBM), an aggressive brain tumor. Matrix (M) protein mutants of VSV have shown greater selectivity for killing GBM cells versus normal brain cells than VSV with wild-type M protein. The goal of this research was to determine the contribution of death receptor and mitochondrial pathways to apoptosis induced by an M protein mutant (M51R) VSV in U87 human GBM tumor cells. Compared to controls, U87 cells expressing a dominant negative form of Fas (dnFas) or overexpressing Bcl-X L had reduced caspase-3 activation following infection with M51R VSV, indicating that both the death receptor pathway and mitochondrial pathways are important for M51R VSV-induced apoptosis. Death receptor signaling has been classified as type I or type II, depending on whether signaling is independent (type I) or dependent on the mitochondrial pathway (type II). Bcl-X L overexpression inhibited caspase activation in response to a Fas-inducing antibody, similar to the inhibition in response to M51R VSV infection, indicating that U87 cells behave as type II cells. Inhibition of apoptosis in vitro delayed, but did not prevent, Virus-induced cell death. Murine xenografts of U87 cells that overexpress Bcl-X L regressed with a time course similar to that of control cells following treatment with M51R VSV, and tumors were not detectable at 21 days postinoculation. Immunohistochemical analysis demonstrated similar levels of viral antigen expression but reduced activation of caspase-3 following Virus treatment of Bcl-X L-overexpressing tumors compared to controls. Further, the pathological changes in tumors following treatment with Virus were quite different in the presence versus the absence of Bcl-X L overexpression. These results demonstrate that M51R VSV efficiently induces oncolysis in GBM tumor cells despite deregulation of apoptotic pathways, underscoring its potential use as a treatment for GBM. Vesicular stomatitis Virus (VSV) is a well-studied negativestrand RNA Virus that has been identified as a potential Oncolytic Virus therapy for brain tumors (29, 30, 51, 53). Oncolytic Virus therapy is an emerging therapy for cancers that currently lack effective treatment (7, 11). Glioblastoma multiforme (GBM) is a common and highly aggressive brain tumor that has a median survival of approximately 1 year once diagnosed (15). Thus, GBM is a cancer that is widely considered likely to benefit from Oncolytic Virus therapy. Several clinical trials of Oncolytic Viruses are ongoing or have already been conducted in patients with GBM (14, 30, 31, 33, 45, 56). To date, at least two VSV Oncolytic Viruses have been considered by the NIH Recombinant DNA Advisory Committee, a key step toward beginning clinical trials in a variety of cancer types (47, 48). The selectivity of VSV for cancerous versus normal tissue is due to defects in antiviral responses that cancers develop
Antonio E Chiocca - One of the best experts on this subject based on the ideXlab platform.
-
effect of tumor microenvironment modulation on the efficacy of Oncolytic Virus therapy
Journal of the National Cancer Institute, 2007Co-Authors: Kazuhiko Kurozumi, Jayson Hardcastle, Roopa Thakur, Ming Yang, Gregory A Christoforidis, Giulia Fulci, Fred H Hochberg, Ralph Weissleder, William E Carson, Antonio E ChioccaAbstract:therapy. Methods Rat glioma cells (D74/HveC) were implanted intracranially in immune-competent rats. Seven days later, the rats (groups of 3 – 7 rats) were treated with Oncolytic Virus (hrR3), and, 3 days later, brains were harvested for evaluation. Some rats were treated with angiostatic cRGD peptide 4 days before Oncolytic Virus treatment. Some rats were treated with cyclophosphamide (CPA), an immunosuppressant, 2 days before Oncolytic Virus treatment. Changes in tumor vascular perfusion were evaluated by magnetic resonance imaging of live rats and by fluorescence microscopy of tumor sections from rats perfused with Texas red – conjugated lectin immediately before euthanasia. Leukocyte infiltration in tumors was evaluated by anti-CD45 immunohistochemistry, and the presence of Oncolytic Virus in tumors was evaluated by viral titration. Changes in cytokine gene expression in tumors were measured by quantitative real-time polymerase chain reaction – based microarrays. Survival was analyzed by the Kaplan – Meier method. All statistical tests were two-sided. Results Oncolytic Virus treatment of experimental rat gliomas increased tumor vascular permeability, host leukocyte infiltration into tumors, and intratumoral expression of inflammatory cytokine genes, including interferon gamma (IFN- ). The increase in vascular permeability was suppressed in rats pretreated with cyclophosphamide. Compared with rats treated with hrR3 alone, rats pretreated with a single dose of cRGD peptide before hrR3 treatment had reduced tumor vascular permeability, leukocyte infiltration, and IFN- protein levels (mean IFN- level for hrR3 versus hrR3 + cRGD = 203 versus 65.6 µ g/mg, difference = 137 µ g/mg, 95% confidence interval = 72.7 to 202.9 µ g/mg, P = .006); increased viral titers in tumor tissue; and longer median survival (21 days versus 17 days, P <.001). Conclusions A single dose of angiostatic cRGD peptide treatment before Oncolytic Virus treatment enhanced the antitu
-
brain tumor oncolysis with replication conditional herpes simplex Virus type 1 expressing the prodrug activating genes cyp2b1 and secreted human intestinal carboxylesterase in combination with cyclophosphamide and irinotecan
Cancer Research, 2005Co-Authors: Edyta Tyminski, Yoshinaga Saeki, Stanley Leroy, Kinya Terada, Dianne M Finkelstein, Janice L Hyatt, Mary K Danks, Philip M Potter, Antonio E ChioccaAbstract:The treatment of malignant glioma is currently ineffective. Oncolytic Viruses are being explored as a means to selectively lyse tumor cells in the brain. We have engineered a mutant herpes simplex Virus type 1 with deletions in the viral UL39 and γ134.5 genes and an insertion of the two prodrug activating genes, CYP2B1 and secreted human intestinal carboxylesterase . Each of these can convert the inactive prodrugs, cyclophosphamide and irinotecan (CPT-11), into their active metabolites, respectively. This new Oncolytic Virus (MGH2) displays increased antitumor efficacy against human glioma cells both in vitro and in vivo when combined with cyclophosphamide and CPT-11. Importantly, cyclophosphamide, CPT-11, or the combination of cyclophosphamide and CPT-11 does not significantly affect Oncolytic Virus replication. Therefore, MGH2 provides effective multimodal therapy for gliomas in preclinical models when combined with these chemotherapy agents.
E. Antonio Chiocca - One of the best experts on this subject based on the ideXlab platform.
-
Oncolytic Viruses on the cusp of success?: proceedings of the 9th International Conference on Oncolytic Virus Therapeutics
Molecular Therapy - Oncolytics, 2016Co-Authors: Cole Peters, E. Antonio Chiocca, Fares Nigim, Samuel D RabkinAbstract:Boston, Massachusetts, was the site of the 9th International Conference on Oncolytic Virus Therapeutics held 13–16 June 2015. An overarching theme of the meeting was the continued development of combinatorial treatment regimens to bolster the therapeutic potential of Oncolytic Viruses (OVs). Several talks focused on combining OVs with immune checkpoint inhibitors in a wide array of tumors, signaling an experimental and thematic shift toward driving immune activation to clear a tumor versus relying on direct viral oncolysis. An important aspect of the meeting was the variety of ongoing OV clinical trials. Topics ranged from basic virology to clinical trials and from academic research to intellectual property and biotechnology. There was much excitement due to the US Food and Drug Administration’s recent consideration of talimogene laherparepvec (T-VEC) for the treatment of advanced melanoma (T-VEC was approved in October, following the conference). Here, we summarize the meeting’s primary themes, which reflect the current state of the field.
-
Effect of Tumor Microenvironment Modulation on the Efficacy of Oncolytic Virus Therapy
Journal of the National Cancer Institute, 2007Co-Authors: Kazuhiko Kurozumi, Jayson Hardcastle, Roopa Thakur, Ming Yang, Gregory A Christoforidis, Giulia Fulci, Fred H Hochberg, Ralph Weissleder, William E Carson, E. Antonio ChioccaAbstract:therapy. Methods Rat glioma cells (D74/HveC) were implanted intracranially in immune-competent rats. Seven days later, the rats (groups of 3 – 7 rats) were treated with Oncolytic Virus (hrR3), and, 3 days later, brains were harvested for evaluation. Some rats were treated with angiostatic cRGD peptide 4 days before Oncolytic Virus treatment. Some rats were treated with cyclophosphamide (CPA), an immunosuppressant, 2 days before Oncolytic Virus treatment. Changes in tumor vascular perfusion were evaluated by magnetic resonance imaging of live rats and by fluorescence microscopy of tumor sections from rats perfused with Texas red – conjugated lectin immediately before euthanasia. Leukocyte infiltration in tumors was evaluated by anti-CD45 immunohistochemistry, and the presence of Oncolytic Virus in tumors was evaluated by viral titration. Changes in cytokine gene expression in tumors were measured by quantitative real-time polymerase chain reaction – based microarrays. Survival was analyzed by the Kaplan – Meier method. All statistical tests were two-sided. Results Oncolytic Virus treatment of experimental rat gliomas increased tumor vascular permeability, host leukocyte infiltration into tumors, and intratumoral expression of inflammatory cytokine genes, including interferon gamma (IFN- ). The increase in vascular permeability was suppressed in rats pretreated with cyclophosphamide. Compared with rats treated with hrR3 alone, rats pretreated with a single dose of cRGD peptide before hrR3 treatment had reduced tumor vascular permeability, leukocyte infiltration, and IFN- protein levels (mean IFN- level for hrR3 versus hrR3 + cRGD = 203 versus 65.6 µ g/mg, difference = 137 µ g/mg, 95% confidence interval = 72.7 to 202.9 µ g/mg, P = .006); increased viral titers in tumor tissue; and longer median survival (21 days versus 17 days, P
-
Cyclophosphamide Allows for In vivo Dose Reduction of a Potent Oncolytic Virus
Cancer research, 2005Co-Authors: Hirokazu Kambara, Yoshinaga Saeki, E. Antonio ChioccaAbstract:The success of cancer virotherapy depends on its efficacy versus toxicity profile in human clinical trials. Progress towards clinical trials can be hampered by the relatively elevated doses of Oncolytic Viruses administered in animal models to achieve an anticancer effect and by the even higher doses required in humans to approximate an animal bioequivalent dose. Such elevated doses of injected viral proteins may also lead to undesirable toxicities and are also very difficult to produce in a biotechnological setting. We report that a relatively potent herpes simplex Virus type 1 Oncolytic Virus (rQNestin34.5) produces 45% survivors at a dose of 3 × 104 plaque-forming units (pfu) in a 9-day-old mouse model of human glioma. Unlike our previous findings with less potent Oncolytic Viruses, though, the preadministration of cyclophosphamide did not enhance this survival or affect Oncolytic Virus tumor distribution and tumor volume. However, when Oncolytic Virus doses were reduced (3 × 103 and 3 × 102 pfu), cyclophosphamide significantly enhanced both animal survival and Oncolytic Virus tumor distribution and also reduced tumor volumes. These findings thus show that cyclophosphamide allows for dose reduction of doses of a relatively potent Oncolytic Virus, a finding with implications for the development of clinical trials. (Cancer Res 2005; 65(24): 11255-8)
Tomoki Todo - One of the best experts on this subject based on the ideXlab platform.
-
Oncolytic Virus therapy in Japan: progress in clinical trials and future perspectives.
Japanese journal of clinical oncology, 2018Co-Authors: Satoru Taguchi, Hiroshi Fukuhara, Tomoki TodoAbstract:Oncolytic Virus therapy is a promising new option for cancer. It utilizes genetically engineered or naturally occurring Viruses that selectively replicate in and kill cancer cells without harming normal cells. T-VEC (talimogene laherparepvec), a second-generation Oncolytic herpes simplex Virus type 1, was approved by the US Food and Drug Administration for the treatment of inoperable melanoma in 2015 and subsequently approved in Europe in 2016. Other Oncolytic Viruses using different parental Viruses have also been tested in Phase III clinical trials and are ready for drug approval: Pexa-Vec (pexastimogene devacirepvec), an Oncolytic vaccinia Virus, CG0070, an Oncolytic adenoVirus, and REOLYSIN (pelareorep), an Oncolytic reoVirus. In Japan, as of May 2018, several Oncolytic Viruses have been developed, and some have already proceeded to clinical trials. In this review, we summarize clinical trials assessing Oncolytic Virus therapy that were conducted or are currently ongoing in Japan, specifically, T-VEC, the abovementioned Oncolytic herpes simplex Virus type 1, G47Δ, a third-generation Oncolytic herpes simplex Virus type 1, HF10, a naturally attenuated Oncolytic herpes simplex Virus type 1, Telomelysin, an Oncolytic adenoVirus, Surv.m-CRA, another Oncolytic adenoVirus, and Sendai Virus particle. In the near future, Oncolytic Virus therapy may become an important and major treatment option for cancer in Japan.
-
Oncolytic Virus therapy: A new era of cancer treatment at dawn
Cancer science, 2016Co-Authors: Hiroshi Fukuhara, Yasushi Ino, Tomoki TodoAbstract:Oncolytic Virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic Viruses are defined as genetically engineered or naturally occurring Viruses that selectively replicate in and kill cancer cells without harming the normal tissues. T-Vec (talimogene laherparepvec), a second-generation Oncolytic herpes simplex Virus type 1 (HSV-1) armed with GM-CSF, was recently approved as the first Oncolytic Virus drug in the USA and Europe. The phase III trial proved that local intralesional injections with T-Vec in advanced malignant melanoma patients can not only suppress the growth of injected tumors but also act systemically and prolong overall survival. Other Oncolytic Viruses that are closing in on drug approval in North America and Europe include vaccinia Virus JX-594 (pexastimogene devacirepvec) for hepatocellular carcinoma, GM-CSF-expressing adenoVirus CG0070 for bladder cancer, and Reolysin (pelareorep), a wild-type variant of reoVirus, for head and neck cancer. In Japan, a phase II clinical trial of G47∆, a third-generation Oncolytic HSV-1, is ongoing in glioblastoma patients. G47∆ was recently designated as a "Sakigake" breakthrough therapy drug in Japan. This new system by the Japanese government should provide G47∆ with priority reviews and a fast-track drug approval by the regulatory authorities. Whereas numerous Oncolytic Viruses have been subjected to clinical trials, the common feature that is expected to play a major role in prolonging the survival of cancer patients is an induction of specific antitumor immunity in the course of tumor-specific viral replication. It appears that it will not be long before Oncolytic Virus therapy becomes a standard therapeutic option for all cancer patients.
-
Oncolytic Virus therapy for prostate cancer
International journal of urology : official journal of the Japanese Urological Association, 2009Co-Authors: Hiroshi Fukuhara, Yukio Homma, Tomoki TodoAbstract:The use of replication-competent Viruses that can selectively replicate in and destroy neoplastic cells is an attractive strategy for treating cancer. Various Oncolytic Viruses have been taken to clinical trials since a recombinant Virus was first applied to cancer patients a decade ago. The concept of the therapy is simple: infectious Virus kills the host cancer cells in the course of viral replication. It is important, however, that the Virus does not harm the surrounding normal tissue. Oncolytic Viruses can be classified largely into two groups: DNA Viruses genetically engineered to achieve cancer specificity (e.g. adenoVirus, herpes simplex Virus and vaccinia) and RNA Viruses of which human is not the natural host (e.g. Newcastle disease Virus and reoVirus). Prostate cancer has always been one of the major targets of Oncolytic Virus therapy development. The result of six clinical trials for prostate cancer has been published and several trials are now going on. Forty-eight of 83 (58%) patients evaluated in the phase I studies demonstrated a >25% decrease in serum prostate-specific antigen level without evidence of severe toxicities. The result shows the Oncolytic Virus therapy is promising toward clinical application. Here, we review the recent advances in the field and summarize the results from clinical trials.
-
Oncolytic Virus therapy for malignant brain tumors
Brain and nerve = Shinkei kenkyu no shinpo, 2009Co-Authors: Yasushi Ino, Tomoki TodoAbstract:Oncolytic Viruses are genetically engineered, recombinant Viruses or naturally occurring, attenuated Viruses that infect, replicate selectively within, and destroy tumor cells. These Viruses are nontoxic to normal tissues, and progeny Viruses released from destroyed tumor cells can spread and infect surrounding tumor cells. In addition, most Oncolytic Viruses can elicit specific antitumor immunity in the course of tumor cell destruction. Currently, the main route of Virus administration is direct intratumoral injection that enables maximum Virus delivery to tumor cells and minimum systemic adverse events. Several types of Oncolytic Viruses have been tested in clinical trials for recurrent malignant glioma, among which genetically engineered herpes simplex Viruses type 1 seems to be the most promising because of its high tumor selectivity (indicating safety) and potency (indicating efficacy). Oncolytic Virus therapy has been developed for various types of cancers other than glioma, including malignant melanoma and prostate, breast, head & neck and colon cancers. Thus far, Oncolytic Viruses that are inoculated intratumorally, are shown to be safe; adverse events typically observed are usually transient and include local inflammation and flu-like symptoms. Oncolytic Viruses can be used in combination with chemotherapy or other conventional therapies, which, in some cases, can lead to synergistic effects. This review summarizes the recent advances in clinical and preclinical research on Oncolytic Virus therapy for malignant brain tumors.
