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Oncolytic immunotherapy

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https://www.readbyqxmd.com/read/27906162/activation-of-myeloid-and-endothelial-cells-by-cd40l-gene-therapy-supports-t-cell-expansion-and-migration-into-the-tumor-microenvironment
#1
E Eriksson, R Moreno, I Milenova, L Liljenfeldt, L C Dieterich, L Christiansson, H Karlsson, G Ullenhag, S Mangsbo, A Dimberg, R Alemany, A Loskog
CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate Th1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer...
December 1, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27895500/efficacy-and-safety-of-talimogene-laherparepvec-versus-granulocyte-macrophage-colony-stimulating-factor-in-patients-with-stage-iiib-c-and-ivm1a-melanoma-subanalysis-of-the-phase-iii-optim-trial
#2
Kevin J Harrington, Robert Hi Andtbacka, Frances Collichio, Gerald Downey, Lisa Chen, Zsolt Szabo, Howard L Kaufman
OBJECTIVES: Talimogene laherparepvec is the first oncolytic immunotherapy to receive approval in Europe, the USA and Australia. In the randomized, open-label Phase III OPTiM trial (NCT00769704), talimogene laherparepvec significantly improved durable response rate (DRR) versus granulocyte-macrophage colony-stimulating factor (GM-CSF) in 436 patients with unresectable stage IIIB-IVM1c melanoma. The median overall survival (OS) was longer versus GM-CSF in patients with earlier-stage melanoma (IIIB-IVM1a)...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27875627/immunotherapy-approaches-in-the-treatment-of-malignant-brain-tumors
#3
REVIEW
Anastasie M Dunn-Pirio, Gordana Vlahovic
Glioblastoma is the most common malignant primary brain tumor. Despite standard-of-care treatment, consisting of maximal surgical resection followed by chemoradiation, both morbidity and mortality associated with this disease remain very poor. Therefore, there is an urgent need for more efficacious and well tolerated therapies. Advancing knowledge of the intricate interplay between malignant gliomas and the immune system, coupled with the recent launch of immunotherapy research for other cancers, has led to a veritable increase in immunotherapy investigation for glioblastoma and other malignant gliomas...
November 22, 2016: Cancer
https://www.readbyqxmd.com/read/27859242/meeting-report-4-th-european-seminars-in-virology-on-oncogenic-and-oncolytic-viruses-in-bertinoro-bologna-italy
#4
Alberto Reale, Lorenzo Messa, Adriana Vitiello, Arianna Loregian, Giorgio Palù
The 4(th) European Seminars in Virology (EuSeV), which was focused on oncogenic and oncolytic viruses, was held in Bertinoro (Bologna), Italy, from June 10 to 12, 2016. This article summarizes the plenary lectures and aims to illustrate the main topics discussed at 4(th) EuSeV, which brought together knowledge and expertise in the field of oncogenic and oncolytic viruses from all over the world. The meeting was divided in two parts, "Mechanisms of Viral Oncogenesis" and "Viral Oncolysis and Immunotherapy", which were both focused on dissecting the complex and multi-factorial interplay between cancer and human viruses and on exploring new anti-cancer strategies...
November 16, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27784340/il-12-expressing-oncolytic-herpes-simplex-virus-promotes-anti-tumor-activity-and-immunologic-control-of-metastatic-ovarian-cancer-in-mice
#5
Eric D Thomas, Selene Meza-Perez, Kerri S Bevis, Troy D Randall, G Yancey Gillespie, Catherine Langford, Ronald D Alvarez
BACKGROUND: Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer. Several studies have demonstrated that ovarian cancer is an immunogenic disease and immunotherapy represents a promising and novel approach that has not been completely evaluated in ovarian cancer...
October 27, 2016: Journal of Ovarian Research
https://www.readbyqxmd.com/read/27769635/immunotherapy-in-melanoma-recent-advances-and-future-directions
#6
C Franklin, E Livingstone, A Roesch, B Schilling, D Schadendorf
Malignant melanoma contributes the majority of skin cancer related deaths and shows an increasing incidence in the past years. Despite all efforts of early diagnosis, metastatic melanoma still has a poor prognosis and remains a challenge for treating physicians. In recent years, improved knowledge of the pathophysiology and a better understanding of the role of the immune system in tumour control have led to the development and approval of several immunotherapies. Monoclonal antibodies against different immune checkpoints have been revolutionizing the treatment of metastatic and unresectable melanoma...
September 2, 2016: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27757313/trial-watch-immunotherapy-plus-radiation-therapy-for-oncological-indications
#7
REVIEW
Erika Vacchelli, Norma Bloy, Fernando Aranda, Aitziber Buqué, Isabelle Cremer, Sandra Demaria, Alexander Eggermont, Silvia Chiara Formenti, Wolf Hervé Fridman, Jitka Fucikova, Jérôme Galon, Radek Spisek, Eric Tartour, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Malignant cells succumbing to some forms of radiation therapy are particularly immunogenic and hence can initiate a therapeutically relevant adaptive immune response. This reflects the intrinsic antigenicity of malignant cells (which often synthesize a high number of potentially reactive neo-antigens) coupled with the ability of radiation therapy to boost the adjuvanticity of cell death as it stimulates the release of endogenous adjuvants from dying cells. Thus, radiation therapy has been intensively investigated for its capacity to improve the therapeutic profile of several anticancer immunotherapies, including (but not limited to) checkpoint blockers, anticancer vaccines, oncolytic viruses, Toll-like receptor (TLR) agonists, cytokines, and several small molecules with immunostimulatory effects...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27660707/into-the-clinic-talimogene-laherparepvec-t-vec-a-first-in-class-intratumoral-oncolytic-viral-therapy
#8
Hasan Rehman, Ann W Silk, Michael P Kane, Howard L Kaufman
With the recent regulatory approval of Talimogene laherparepvec (T-VEC) for the treatment of advanced of melanoma in the United States, Europe and Australia, oncolytic virus immunotherapy has earned its place in the clinic. However, the adoption of T-VEC by the U.S. oncology community has been slow, and so far has been largely limited to specialized cancer centers. Limiting factors include the intratumoral route of administration, which is unfamiliar to medical oncologists, biosafety concerns related to the use of a live virus in the clinic, and the explosion of other therapeutic strategies now available for the treatment of advanced melanoma...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27637889/safe-and-effective-treatment-of-experimental-neuroblastoma-and-glioblastoma-using-systemically-administered-triple-microrna-detargeted-oncolytic-semliki-forest-virus
#9
Mohanraj Ramachandran, Di Yu, Matheus Dyczynski, Sathishkumar Baskaran, Lei Zhang, Sirle Saul, Aleksei Lulla, Valeria Lulla, Sven Nelander, Anna Dimberg, Andres Merits, Justyna Leja-Jarblad, Magnus Essand
PURPOSE: Glioblastoma multiforme (GBM) and high-risk neuroblastoma are cancers with poor outcome. Immunotherapy in the form of neurotropic oncolytic viruses is a promising therapeutic strategy for these malignancies. Here we evaluate the oncolytic potential of the neurovirulent and partly interferon (IFN)-β-resistant Semliki Forest virus (SFV)-4 in GBMs and neuroblastomas. To reduce neurovirulence we constructed SFV4miRT, which is attenuated in normal CNS cells through insertion of microRNA target sequences for miR124, miR125, miR134 Experimental Design:Oncolytic activity of SFV4miRT was examined in mouse neuroblastoma and GBM cell lines and in patient-derived human glioblastoma cell cultures (HGCC)...
September 16, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27622065/interferon-alpha-bioactivity-critically-depends-on-scavenger-receptor-class-b-type-i-function
#10
Marcos Vasquez, Jessica Fioravanti, Fernando Aranda, Vladimir Paredes, Celia Gomar, Nuria Ardaiz, Veronica Fernandez-Ruiz, Miriam Méndez, Estanislao Nistal-Villan, Esther Larrea, Qinshan Gao, Gloria Gonzalez-Aseguinolaza, Jesus Prieto, Pedro Berraondo
Scavenger receptor class B type I (SR-B1) binds pathogen-associated molecular patterns participating in the regulation of the inflammatory reaction but there is no information regarding potential interactions between SR-B1 and the interferon system. Herein, we report that SR-B1 ligands strongly regulate the transcriptional response to interferon α (IFNα) and enhance its antiviral and antitumor activity. This effect was mediated by the activation of TLR2 and TLR4 as it was annulled by the addition of anti-TLR2 or anti-TLR4 blocking antibodies...
August 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27579293/high-throughput-screening-to-enhance-oncolytic-virus-immunotherapy
#11
REVIEW
K J Allan, David F Stojdl, S L Swift
High-throughput screens can rapidly scan and capture large amounts of information across multiple biological parameters. Although many screens have been designed to uncover potential new therapeutic targets capable of crippling viruses that cause disease, there have been relatively few directed at improving the efficacy of viruses that are used to treat disease. Oncolytic viruses (OVs) are biotherapeutic agents with an inherent specificity for treating malignant disease. Certain OV platforms - including those based on herpes simplex virus, reovirus, and vaccinia virus - have shown success against solid tumors in advanced clinical trials...
2016: Oncolytic Virotherapy
https://www.readbyqxmd.com/read/27579292/cancer-immunotherapy-via-combining-oncolytic-virotherapy-with-chemotherapy-recent-advances
#12
REVIEW
Guy R Simpson, Kate Relph, Kevin Harrington, Alan Melcher, Hardev Pandha
Oncolytic viruses are multifunctional anticancer agents with huge clinical potential, and have recently passed the randomized Phase III clinical trial hurdle. Both wild-type and engineered viruses have been selected for targeting of specific cancers, to elicit cytotoxicity, and also to generate antitumor immunity. Single-agent oncolytic virotherapy treatments have resulted in modest effects in the clinic. There is increasing interest in their combination with cytotoxic agents, radiotherapy and immune-checkpoint inhibitors...
2016: Oncolytic Virotherapy
https://www.readbyqxmd.com/read/27563660/future-perspectives-in-cancer-immunotherapy
#13
Marinos Tsiatas, Giannis Mountzios, Giuseppe Curigliano
The advent of immunotherapy has transformed the treatment paradigm of several solid tumors and is expected to influence the therapeutic algorithm even more in the future following the results of numerous ongoing clinical trials in a wide range of malignancies. Exploiting the anti-cancer effect of the immune system with the use of vaccines, viral vectors, and more lately with immune check-point inhibitors and chimeric antigen receptor modification, has been proven a successful therapeutic strategy in a broad spectrum of tumors...
July 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27563648/harnessing-the-immune-system-to-improve-cancer-therapy
#14
REVIEW
Nikos E Papaioannou, Ourania V Beniata, Panagiotis Vitsos, Ourania Tsitsilonis, Pinelopi Samara
Cancer immunotherapy uses the immune system and its components to mount an anti-tumor response. During the last decade, it has evolved from a promising therapy option to a robust clinical reality. Many immunotherapeutic modalities are already approved by the Food and Drug Administration (FDA) for treating cancer patients and many others are in the pipeline for approval as standalone or combinatorial therapeutic interventions, several also combined with standard treatments in clinical studies. The two main axes of cancer immunotherapeutics refer to passive and active treatments...
July 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27521450/immunotherapy-gone-viral-bortezomib-and-ohsv-enhance-antitumor-nk-cell-activity
#15
Carter M Suryadevara, Katherine A Riccione, John H Sampson
Oncolytic viruses, proteasome inhibitors, and natural killer (NK)-cell immunotherapy have all been studied extensively as monotherapies but have never been evaluated in combination. Synergetic treatment of oncolytic virus-infected glioblastomas with a proteasome inhibitor induces necroptotic cell death to enhance NK-cell immunotherapy, prolonging survival against human glioblastoma. Clin Cancer Res; 22(21); 5164-6. ©2016 AACRSee related article by Yoo et al., p. 5265.
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27516203/talimogene-laherparepvec-a-review-in-unresectable-metastatic-melanoma
#16
Karly P Garnock-Jones
Talimogene laherparepvec (Imlygic™) is a first-in-class oncolytic viral immunotherapy derived from herpes simplex virus type 1, which has been genetically modified to increase tumour selectivity and stimulate antitumour immune response. This article reviews the pharmacological properties of intralesional talimogene laherparepvec and its clinical efficacy and tolerability in patients with unresectable metastatic melanoma. In the phase III OPTiM trial, talimogene laherparepvec was more effective than subcutaneous human granulocyte-macrophage colony-stimulating factor (GM-CSF), both in patients with stage IIIB-IV melanoma [intention-to-treat (ITT) population] and in those with stage IIIB-IVM1a disease (in an exploratory subgroup analysis)...
October 2016: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/27514721/immunotherapy-of-melanoma
#17
D Kee, G McArthur
Immunotherapy for advanced melanoma has progressed dramatically in the last five years with the approval of immune checkpoint inhibitors targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Inhibition of these targets can break cancer-immune tolerance and result in durable objective responses with significantly improved tolerability over cytokine-based immunotherapy. Ipilimumab is an inhibitor of CTLA-4 and the first-in-class immune checkpoint inhibitor to demonstrate an improvement in overall survival in melanoma...
August 2, 2016: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27492706/oncolytic-viruses-immunotherapeutics-on-the-rise
#18
REVIEW
Brian A Keller, John C Bell
The oncolytic virus (OV) field has entered an exciting period in its evolution in which our basic understanding of viral biology and anti-cancer potential are being actively translated into viable therapeutic options for aggressive malignancies. OVs are naturally occurring or engineered viruses that are able to exploit cancer-specific changes in cellular signaling to specifically target cancers and their microenvironment. The direct cytolytic effect of OVs on cancer cells is known to release antigens, which can begin a cascade of events that results in the induction of anti-cancer adaptive immunity...
September 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27486853/oncolytic-virus-therapy-a-new-era-of-cancer-treatment-at-dawn
#19
Hiroshi Fukuhara, Yasushi Ino, Tomoki Todo
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...
August 3, 2016: Cancer Science
https://www.readbyqxmd.com/read/27460757/immunotherapy-for-the-treatment-of-urothelial-carcinoma
#20
REVIEW
Nicholas M Donin, Andrew T Lenis, Stuart Holden, Alexandra Drakaki, Allan Pantuck, Arie Belldegrun, Karim Chamie
PURPOSE: We review the biological mechanisms of action, clinical safety and efficacy of immunotherapies for urothelial carcinoma. We also describe current areas of research in immunotherapy, and highlight ongoing trials and promising and novel investigational agents. MATERIALS AND METHODS: Data were obtained by a search of PubMed®, ClinicalTrials.gov and Cochrane databases for English language articles published through February 2016. Applicable abstracts from recent Society of Urologic Oncology, European Association of Urology, American Urological Association and ASCO® meetings were used...
July 25, 2016: Journal of Urology
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