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Oncolytic immunotherapy

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https://www.readbyqxmd.com/read/29137714/checkpoint-blockade-plus-oncolytic-virus-a-hot-therapeutic-cancer-strategy
#1
Caroline Robert
How can we transform an immune desert into a 'hot tumor' that is prone to respond to anti-programmed death (PD)-1 immunotherapy? This might be possible by injecting an oncolytic virus, engineered to induce local immune stimulation, prior to anti-PD-1 therapy. A recent study demonstrated that this combination - evaluated in a Phase Ib metastatic melanoma clinical study - yields promising results.
November 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29123084/re-designing-interleukin-12-to-enhance-its-safety-and-potential-as-an-anti-tumor-immunotherapeutic-agent
#2
Pengju Wang, Xiaozhu Li, Jiwei Wang, Dongling Gao, Yuenan Li, Haoze Li, Yongchao Chu, Zhongxian Zhang, Hongtao Liu, Guozhong Jiang, Zhenguo Cheng, Shengdian Wang, Jianzeng Dong, Baisui Feng, Louisa S Chard, Nicholas R Lemoine, Yaohe Wang
Interleukin-12 (IL-12) has emerged as one of the most potent agents for anti-tumor immunotherapy. However, potentially lethal toxicity associated with systemic administration of IL-12 precludes its clinical application. Here we redesign the molecule in such a way that its anti-tumor efficacy is not compromised, but toxic effects are eliminated. Deletion of the N-terminal signal peptide of IL-12 can effect such a change by preventing IL-12 secretion from cells. We use a newly designed tumor-targeted oncolytic adenovirus (Ad-TD) to deliver non-secreting (ns) IL-12 to tumor cells and examine the therapeutic and toxic effects in Syrian hamster models of pancreatic cancer (PaCa)...
November 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/29061083/immuno-oncology-the-translational-runway-for-gene-therapy
#3
Ludger Weß, Frank Schnieders
Cancer therapy once again is experiencing a paradigm shift. This shift is based on extensive clinical experience demonstrating that cancer cannot be successfully fought by addressing single targets or pathways only. Even the combination of several neo-antigens in cancer vaccines is not sufficient for a successful, lasting tumor eradication. The focus therefore has shifted on the immune systems role in cancer and the striking abilities of cancer cells to manipulate and/or deactivate the immune system. Researchers and pharma companies have started to target the processes and cells known to support immune surveillance and the elimination of tumor cells...
October 23, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29034314/targeting-an-oncolytic-influenza-a-virus-to-tumor-tissue-by-elastase
#4
Irina Kuznetsova, Tobias Arnold, Thomas Aschacher, Cornelia Schwager, Balazs Hegedus, Tamas Garay, Marina Stukova, Maria Pisareva, Stephan Pleschka, Michael Bergmann, Andrej Egorov
Oncolytic viruses are currently established as a novel type of immunotherapy. The challenge is to safely target oncolytic viruses to tumors. Previously, we have generated influenza A viruses (IAVs) containing deletions in the viral interferon antagonist. Those deletions have attenuated the virus in normal tissue but allowed replication in tumor cells. IAV entry is mediated by hemagglutinin (HA), which needs to be activated by a serine protease, for example, through trypsin. To further target the IAV to tumors, we have changed the trypsin cleavage site to an elastase cleavage site...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29034312/tgf-%C3%AE-inhibition-improves-oncolytic-herpes-viroimmunotherapy-in-murine-models-of-rhabdomyosarcoma
#5
Brian Hutzen, Chun-Yu Chen, Pin-Yi Wang, Les Sprague, Hayley M Swain, Julia Love, Joe Conner, Louis Boon, Timothy P Cripe
Oncolytic viruses are an emerging class of cancer therapeutics that couple cytotoxicity with the induction of an anti-tumor immune response. Host-virus interactions are complex and modulated by a tumor microenvironment whose immunosuppressive activities can limit the effectiveness of cancer immunotherapies. In an effort to improve this aspect of oncolytic virotherapy, we combined the oncolytic herpes virus HSV1716 with the transforming growth factor beta receptor 1 (TGF-βR1) inhibitor A8301 to treat syngeneic models of murine rhabdomyosarcoma...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29029813/innovative-therapy-monoclonal-antibodies-and-beyond
#6
M Di Nicola, L Apetoh, M Bellone, M P Colombo, G Dotti, S Ferrone, M Muscolini, J Hiscott, A Anichini, S M Pupa, F de Braud, M Del Vecchio
The seventh Edition of "Innovative Therapy, Monoclonal Antibodies and Beyond" Meeting took place in Milan, Italy, on January 27, 2017. The two sessions of the meeting were focused on: 1) Preclinical assays and novel biotargets; and 2) monoclonal antibodies, cell therapies and targeted molecules. Between these two sessions, a lecture entitled "HLA-antigens modulation and response to immune checkpoint inhibitor immunotherapy" was also presented. Despite the impressive successes in cancer immunotherapy in recent years, the response to immune based interventions occurs only in a minority of patients (∼20%)...
October 5, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28967094/the-inducers-of-immunogenic-cell-death-for-tumor-immunotherapy
#7
Xiuying Li
Immunotherapy is a promising treatment modality that acts by selectively harnessing the host immune defenses against cancer. An effective immune response is often needed to eliminate tumors following treatment which can trigger the immunogenicity of dying tumor cells. Some treatment modalities (such as photodynamic therapy, high hydrostatic pressure or radiotherapy) and agents (some chemotherapeutic agents, oncolytic viruses) have been used to endow tumor cells with immunogenicity and/or increase their immunogenicity...
September 18, 2017: Tumori
https://www.readbyqxmd.com/read/28955655/oncolytic-viruses-natural-and-genetically-engineered-cancer-immunotherapies
#8
REVIEW
Sachin R Jhawar, Aditya Thandoni, Praveen K Bommareddy, Suemair Hassan, Frederick J Kohlhapp, Sharad Goyal, Jason M Schenkel, Ann W Silk, Andrew Zloza
There has long been interest in innovating an approach by which tumor cells can be selectively and specifically targeted and destroyed. The discovery of viruses that lyse tumor cells, termed oncolytic viruses (OVs), has led to a revolution in the treatment of cancer. The potential of OVs to improve the therapeutic ratio is derived from their ability to preferentially infect and replicate in cancer cells while avoiding destruction of normal cells surrounding the tumor. Two main mechanisms exist through which these viruses are reported to improve outcomes: direct lysis of tumor cells and indirect augmentation of host anti-tumor immunity...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28940544/chronic-granulomatous-dermatitis-induced-by-talimogene-laherparepvec-therapy-of-melanoma-metastases
#9
Ashlyn S Everett, Peter G Pavlidakey, Carlo M Contreras, Jennifer F De Los Santos, Ju Y Kim, Svetlana B McKee, Howard L Kaufman, Robert M Conry
Talimogene laherparepvec is the first oncolytic viral immunotherapy approved by the FDA, for advanced melanoma consisting of genetically modified herpes simplex type 1 virus which selectively replicates causing tumor lysis, expressing GM-CSF and activating dendritic cells. Intratumoral injection of TVEC produces objective response in 41% of stage IIB-IV M1a melanoma. However, clinical response assessments can be problematic due to immune-related inflammation at established tumor sites. Herein, we report 5 cases of granulomatous dermatitis developing at sites of TVEC injection associated with pathologic complete response in 4 of 5 patients...
September 22, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28923101/durable-response-rate-as-an-endpoint-in-cancer-immunotherapy-insights-from-oncolytic-virus-clinical-trials
#10
Howard L Kaufman, Robert H I Andtbacka, Frances A Collichio, Michael Wolf, Zhongyun Zhao, Mark Shilkrut, Igor Puzanov, Merrick Ross
BACKGROUND: 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. METHODS: 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...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28922411/cytokine-induced-killer-cell-delivery-enhances-the-antitumor-activity-of-oncolytic-reovirus
#11
Xing Zhao, Weiwei Ouyang, Cariad Chester, Shiqi Long, Nianxue Wang, Zhixu He
Oncolytic viruses (OV) have recently emerged as a promising therapeutic modality in cancer treatment. OV selectively infect and kill tumor cells, while sparing untransformed cells. The direct cytotoxic effects combined with the capacity to trigger an immune response make OV an appealing combination partner in the burgeoning field of cancer immunotherapy. One of the leading OV therapeutic candidates is the double-stranded RNA virus reovirus. In order to improve the oncolytic activity of reovirus and allow for systemic administration despite the prevalence of neutralizing antibodies, cytokine-induced killer (CIK) cells were explored as cell carriers for reovirus delivery...
2017: PloS One
https://www.readbyqxmd.com/read/28920000/oncolytic-peptide-ltx-315-induces-an-immune-mediated-abscopal-effect-in-a-rat-sarcoma-model
#12
Janne Nestvold, Meng-Yu Wang, Ketil A Camilio, Severin Zinöcker, Torunn Elisabeth Tjelle, Alf Lindberg, Bengt Erik Haug, Gunnar Kvalheim, Baldur Sveinbjørnsson, Øystein Rekdal
LTX 315 is an oncolytic peptide with potent immunological properties. In the present study, we demonstrate that intratumoral treatment with LTX-315 resulted in a complete regression and systemic immune response in a rat fibrosarcoma model. The treatment was T-cell dependent, and also resulted in an abscopal effect as demonstrated by the regression of distal non-treated lesions. Significant infiltration of CD8(+) T cells was observed in both treated and non-treated lesions, as shown by immunohistochemical and flow cytometric analysis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28912872/preclinical-trial-of-the-multi-targeted-lenvatinib-in-combination-with-cellular-immunotherapy-for-treatment-of-renal-cell-carcinoma
#13
Chengkuan Cai, Jingyuan Tang, Baixin Shen, Liucheng Ding, Yunpeng Shao, Zhengsen Chen, Yinchao Ma, Haoliang Xue, Zhongqing Wei
Lenvatinib is an oral, multi-targeted tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor β, RET and KIT. Cellular immunotherapy has the potential to be a highly targeted treatment, with low toxicity to normal tissues and a high capacity to eradicate tumor tissue. The present study assessed the safety, maximum tolerated dose (MTD) and preliminary antitumor activity of lenvatinib and cellular immunotherapy in a murine model of renal cell carcinoma (RCC)...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28912369/customized-viral-immunotherapy-for-hpv-associated-cancer
#14
Matthew J Atherton, Kyle B Stephenson, Jonathan Pol, Fuan Wang, Charles Lefebvre, David F Stojdl, Jake K Nikota, Anna Dvorkin-Gheva, Andrew Nguyen, Lan Chen, Stephanie Johnson-Obaseki, Patrick J Villeneuve, Jean-Simon Diallo, Jim Dimitroulakos, Yonghong Wan, Brian D Lichty
The viral-transforming proteins E6 and E7 make human papillomavirus-positive (HPV(+)) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multifunctional CD8(+) T-cell responses...
October 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28902983/solid-tumor-immunotherapy-with-t-cell-engager-armed-oncolytic-viruses
#15
REVIEW
Eleanor M Scott, Margaret R Duffy, Joshua D Freedman, Kerry D Fisher, Leonard W Seymour
Oncolytic viruses (OVs) are novel anticancer agents that combine direct cancer cell killing with the stimulation of antitumor immunity. In addition, OVs can be engineered to deliver biological therapeutics directly to tumors, offering unique opportunities to design multimodal anticancer strategies. Here, a case for arming OVs with bispecific T cell engagers (BiTEs) is put forward. BiTEs redirect the cytotoxicity of polyclonal T cells to target cells of choice, and have demonstrated efficacy against a number of hematological cancers...
September 13, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28886381/oncolytic-virotherapy-promotes-intratumoral-t-cell-infiltration-and-improves-anti-pd-1-immunotherapy
#16
Antoni Ribas, Reinhard Dummer, Igor Puzanov, Ari VanderWalde, Robert H I Andtbacka, Olivier Michielin, Anthony J Olszanski, Josep Malvehy, Jonathan Cebon, Eugenio Fernandez, John M Kirkwood, Thomas F Gajewski, Lisa Chen, Kevin S Gorski, Abraham A Anderson, Scott J Diede, Michael E Lassman, Jennifer Gansert, F Stephen Hodi, Georgina V Long
Here we report a phase 1b clinical trial testing the impact of oncolytic virotherapy with talimogene laherparepvec on cytotoxic T cell infiltration and therapeutic efficacy of the anti-PD-1 antibody pembrolizumab. Twenty-one patients with advanced melanoma were treated with talimogene laherparepvec followed by combination therapy with pembrolizumab. Therapy was generally well tolerated, with fatigue, fevers, and chills as the most common adverse events. No dose-limiting toxicities occurred. Confirmed objective response rate was 62%, with a complete response rate of 33% per immune-related response criteria...
September 7, 2017: Cell
https://www.readbyqxmd.com/read/28884088/oncolytic-viral-therapy-for-mesothelioma
#17
REVIEW
Daniel F Pease, Robert A Kratzke
The limited effectiveness of conventional therapy for malignant pleural mesothelioma demands innovative approaches to this difficult disease. Even with aggressive multimodality treatment of surgery, radiation, and/or chemotherapy, the median survival is only 1-2 years depending on stage and histology. Oncolytic viral therapy has emerged in the last several decades as a rapidly advancing field of immunotherapy studied in a wide spectrum of malignancies. Mesothelioma makes an ideal candidate for studying oncolysis given the frequently localized pattern of growth and pleural location providing access to direct intratumoral injection of virus...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28870120/virotherapy-research-in-germany-from-engineering-to-translation-a-review-as-contribution-to-the-combined-annual-meeting-of-the-german-and-european-societies-of-gene-and-cell-therapy-2017
#18
Guy Ungerechts, Christine E Engeland, Christian J Buchholz, Jürgen Eberle, Henry Fechner, Karsten Geletneky, Per Sonne Holm, Florian Kreppel, Florian Kühnel, Karl Sebastian Lang, Mathias F Leber, Antonio Marchini, Markus Moehler, Michael D Mühlebach, Jean Rommelaere, Christoph Springfeld, Ulrich M Lauer, Dirk M Nettelbeck
Virotherapy is a unique modality for treatment of cancer with oncolytic viruses (OVs) that selectively infect and lyse tumor cells, spread within tumors, and activate anti-tumor immunity. Different viruses are being developed as OVs preclinically and clinically, several of them engineered to encode therapeutic proteins for tumor-targeted gene therapy. Scientists and clinicians in Germany have made significant contributions to OV research and development, which are highlighted in this review article. Innovative strategies for "shielding", entry- or post-entry targeting, and "arming" of OVs have been established focusing on adeno-, measles, parvo-, and vaccinia virus platforms...
September 4, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28837095/editorial-of-the-special-issue-oncolytic-viruses-as-a-novel-form-of-immunotherapy-for-cancer
#19
EDITORIAL
Zong Sheng Guo, David L Bartlett
Oncolytic viruses (OVs), either occurring naturally or through genetic engineering, can selectively infect, replicate in, and kill cancer cells, while leaving normal cells (almost) unharmed [...].
August 24, 2017: Biomedicines
https://www.readbyqxmd.com/read/28829151/validation-of-an-immunohistochemistry-assay-for-detection-of-cd155-the-poliovirus-receptor-in-malignant-gliomas
#20
Vidyalakshmi Chandramohan, Jeffrey D Bryant, Hailan Piao, Stephen T Keir, Eric S Lipp, Michaela Lefaivre, Kathryn Perkinson, Darell D Bigner, Matthias Gromeier, Roger E McLendon
CONTEXT: - The oncolytic polio-rhinovirus recombinant (PVSRIPO) has demonstrated promise in currently ongoing phase I/II clinical trials against recurrent glioblastoma and was granted breakthrough therapy designation by the Food and Drug Administration/Center for Biologics Evaluation and Research. A reliable clinical assay to document expression of the poliovirus receptor, CD155, in routinely available patient tumor samples is needed for continued clinical development of PVSRIPO oncolytic immunotherapy in primary brain tumors and beyond...
August 22, 2017: Archives of Pathology & Laboratory Medicine
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