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Oncolytic immunotherapy

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https://www.readbyqxmd.com/read/28074746/oncology-s-trojan-horse-using-viruses-to-battle-cancer
#1
Heena J Mavani, Jeannette Y Wick
: In 2016, the American health care system was faced with more than 1.6 million new cases of cancer, and individuals older than 65 years of age will be affected disproportionately. Many older individuals are poor candidates for traditional treatments (e.g., chemotherapy, radiation) because of actual or potential treatment-related adverse events. Researchers continuously look for novel therapeutic strategies, and an exciting new one is on the horizon: virotherapy. Viruses' ability to infect and kill human cells makes them promising cancer treatments...
December 1, 2016: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
https://www.readbyqxmd.com/read/28052356/an-overview-of-the-changing-landscape-of-treatment-for-advanced-melanoma
#2
Chung-Shien Lee, Christan M Thomas, Kimberly E Ng
Melanoma-the deadliest form of skin cancer-leads to thousands of deaths each year. Although melanoma is less common than basal cell and squamous cell skin cancers, melanoma is more dangerous because it is more likely to spread to other parts of the body, such as lymph nodes, if not diagnosed and treated early. Data from the National Cancer Institute indicate a steady rise in new cases of melanoma and, unfortunately, a steady rate in the number of deaths through 2013. Ninety percent of melanomas are linked to inadequate sun protection from ultraviolet rays or the tanning habits of young adults...
January 4, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28004928/iterative-design-and-in-vivo-evaluation-of-an-oncolytic-antilymphoma-peptide
#3
J Johannes Eksteen, Dominik Ausbacher, Jaione Simon-Santamaria, Trine Stiberg, Cristiane Cavalcanti-Jacobsen, Imin Wushur, John S Svendsen, Øystein Rekdal
Oncolytic peptides represent a promising new strategy within the field of cancer immunotherapy. Here we describe the systematic design and evaluation of short antilymphoma peptides within this paradigm. The peptides were tested in vitro and in vivo to identify a lead compound for further evaluation as novel oncolytic immunotherapeutic. In vitro tests revealed peptides with high activity against several lymphoma types and low cytotoxicity toward normal cells. Treated lymphoma cells exhibited a reduced mitochondrial membrane potential that resulted in an irreversible disintegration of their plasma membranes...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28002796/oncolytic-adenovirus-coexpressing-interleukin-12-and-decorin-overcomes-treg-mediated-immunosuppression-inducing-potent-antitumor-effects-in-a-weakly-immunogenic-tumor-model
#4
Eonju Oh, Il-Kyu Choi, JinWoo Hong, Chae-Ok Yun
Interleukin (IL)-12 is a potent antitumor cytokine. However, immunosuppressive tumor microenvironments containing transforming growth factor-β (TGF-β) attenuate cytokine-mediated antitumor immune responses. To enhance the efficacy of IL-12-mediated cancer immunotherapy, decorin (DCN) was explored as an adjuvant for overcoming TGF-β-mediated immunosuppression. We designed and generated a novel oncolytic adenovirus (Ad) coexpressing IL-12 and DCN (RdB/IL12/DCN). RdB/IL12/DCN-treated tumors showed significantly greater levels of interferon (IFN)-γ, tumor necrosis factor-α, monocyte chemoattractant protein-1, and IFN-γ-secreting immune cells than tumors treated with cognate control oncolytic Ad expressing a single therapeutic gene (RdB/DCN or RdB/IL12)...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27993115/virus-oncolytic-virus-and-human-prostate-cancer
#5
Guang Bin Liu, Liang Zhao, Lifang Zhang, Kong-Nan Zhao
Prostate cancer (PCa), a disease, is characterized by abnormal cell growth in the prostate - a gland in the male reproductive system. PCa is one of the leading causes of cancer death among men of all races. Although older age and a family history of the disease have been recognized as the risk factors of PCa, the cause of this cancer remains unclear. Mounting evidence suggests that infections with various viruses are causally linked to PCa pathogenesis. Published studies have provided strong evidence that at least two viruses (RXMV and HPV) contribute to prostate tumourigenicity and impact on the survival of patients with malignant PCa...
December 15, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27989216/the-safety-of-talimogene-laherparepvec-for-the-treatment-of-advanced-melanoma
#6
Alexandra Gangi, Jonathan S Zager
Talimogene laherparepvec (T-VEC, IMLYGIC) is an oncolytic herpes virus type I used as intralesional therapy for the treatment of unresectable metastatic melanoma in a cutaneous, subcutaneous, or nodal location. Talimogene laherparepvec selectively replicates within and lyses tumor cells while producing granulocyte macrophage colony-stimulating factor (GM-CSF), which may promote an immune mediated antitumor response. Areas covered: The US Food and Drug Administration approved Talimogene laherparepvec in late 2015 following the completion of phase I, II and III trials that demonstrated safety and efficacy...
December 28, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27988837/talimogene-laherparepvec-t-vec-and-other-oncolytic-viruses-for-the-treatment-of-melanoma
#7
Praveen K Bommareddy, Anand Patel, Saamia Hossain, Howard L Kaufman
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...
December 17, 2016: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/27922859/fdg-pet-ct-for-monitoring-response-of-melanoma-to-the-novel-oncolytic-viral-therapy-talimogene-laherparepvec
#8
Matthew F Covington, Clara N Curiel, Lois Lattimore, Ryan J Avery, Phillip H Kuo
61-year-old woman with stage IIIa (T3a N1a M0) left lower leg melanoma with lesions suggestive of in-transit metastases 8 months following wide local excision and femoral nodal dissection. FDG-PET/CT demonstrated 5 FDG-avid in-transit nodal metastases in the distal left leg, confirmed on biopsy. Talimogene laherparepvec (T-VEC) oncolytic immunotherapy consisting of intralesional injections of modified herpes simplex virus-expressing granulocyte-macrophage colony-stimulating factor was completed over 6 months...
December 3, 2016: Clinical Nuclear Medicine
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
REVIEW
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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