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Oncolytic immunotherapy

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https://www.readbyqxmd.com/read/29785403/immunotherapy-for-hepatocellular-carcinoma-current-advances-and-future-expectations
#1
REVIEW
Yingjun Xie, Yien Xiang, Jiyao Sheng, Dan Zhang, Xiaoxiao Yao, Yongsheng Yang, Xuewen Zhang
Primary liver cancer is a common kind of digestive cancers with high malignancy, causing 745,500 deaths each year. Hepatocellular carcinoma is the major pathological type of primary liver cancer. Traditional treatment methods for patients with hepatocellular carcinoma have shown poor efficacy in killing residual cancer cells for a long time. In recent years, tumor immunotherapy has emerged as a promising method owing to its safety and efficacy with respect to delaying the progression of advanced tumors and protecting postoperative patients against tumor relapse and metastasis...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29764498/talimogene-laherparepvec-combined-with-anti-pd-1-based-immunotherapy-for-unresectable-stage-iii-iv-melanoma-a-case-series
#2
Lillian Sun, Pauline Funchain, Jung Min Song, Patricia Rayman, Charles Tannenbaum, Jennifer Ko, Michael Mcnamara, C Marcela Diaz-Montero, Brian Gastman
BACKGROUND: Talimogene Laherparepvec (T-VEC) is an oncolytic virus approved as an intratumoral therapy for treating unresectable stage IIIB-IV metastatic melanoma. The mechanisms of action for T-VEC and checkpoint inhibitor are highly complementary. Recent studies have shown that combining checkpoint inhibitor therapy with T-VEC injection can lead to improved response rates for stage IIIB-IV melanoma patients. METHODS: We reviewed 10 consecutive cases of stage IIIC to stage IVM1b melanoma patients that received T-VEC plus checkpoint inhibitor(s) therapy (pembrolizumab, ipilimumab/nivolumab, or nivolumab) treated between June 2016 and August 2017 at the Cleveland Clinic with a median follow-up of 7 months (range: 4 to 13 months)...
May 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29743717/integrating-oncolytic-viruses-in-combination-cancer-immunotherapy
#3
REVIEW
Praveen K Bommareddy, Megha Shettigar, Howard L Kaufman
Oncolytic viruses can be usefully integrated into tumour immunotherapies, as they target multiple steps within the cancer-immunity cycle. Oncolytic viruses directly lyse tumour cells, leading to the release of soluble antigens, danger signals and type I interferons, which drive antitumour immunity. In addition, some oncolytic viruses can be engineered to express therapeutic genes or can functionally alter tumour-associated endothelial cells, further enhancing T cell recruitment into immune-excluded or immune-deserted tumour microenvironments...
May 9, 2018: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/29735917/cancer-immunotherapy-a-focus-on-the-regulation-of-immune-checkpoints
#4
REVIEW
Tao Shi, Yanyu Ma, Lingfeng Yu, Jiaxuan Jiang, Sunan Shen, Yayi Hou, Tingting Wang
In recent years, the role of cancer immunotherapy has become increasingly important compared to traditional cancer treatments, including surgery, chemotherapy and radiotherapy. Of note, the clinical successes of immune checkpoint blockade, such as PD-1 and CTLA-4, represent a landmark event in cancer immunotherapy development. Therefore, further exploration of how immune checkpoints are regulated in the tumor microenvironment will provide key insights into checkpoint blockade therapy. In this review, we discuss in details about the regulation of immune checkpoints mediated by immune cells, oncolytic viruses, epigenetics, and gut microbiota and mutual regulation by co-expressed checkpoints...
May 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29731836/overexpression-of-p53-delivered-using-recombinant-ndv-induces-apoptosis-in-glioma-cells-by-regulating-the-apoptotic-signaling-pathway
#5
Xiaoyong Fan, Hongzhen Lu, Youqiang Cui, Xianzeng Hou, Chuanjiang Huang, Guangcun Liu
Malignant glioma is the most common primary brain carcinoma in the world and has a poor survival rate. Previous studies have demonstrated that p53 dysfunction contributes to the development and severity of malignant glioma. It has also been demonstrated that Newcastle disease virus (NDV) may be a viable candidate for the treatment of various types of cancer. In the present study, a p53 oncolytic agent delivered using recombinant NDV (rNDV-p53) was constructed and its anti-tumor effects in vitro and in vivo were assessed...
May 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29728690/publisher-correction-oncolytic-viruses-as-engineering-platforms-for-combination-immunotherapy
#6
Kwame Twumasi-Boateng, Jessica L Pettigrew, Y Y Eunice Kwok, John C Bell, Brad H Nelson
In the online html version of this article, the affiliations for Jessica L. Pettigrew and John C. Bell were not correct. Jessica L. Pettigrew is at the Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada and John C. Bell is at the Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. This is correct in the print and PDF versions of the article and has been corrected in the html version.
May 4, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29724655/lighting-a-fire-in-the-tumor-microenvironment-using-oncolytic-immunotherapy
#7
REVIEW
Carole Achard, Abera Surendran, Marie-Eve Wedge, Guy Ungerechts, John Bell, Carolina S Ilkow
Oncolytic virus (OV) therapy is potentially a game-changing cancer treatment that has garnered significant interest due to its versatility and multi-modal approaches towards tumor eradication. In the field of cancer immunotherapy, the immunological phenotype of the tumor microenvironment (TME) is an important determinant of disease prognosis and therapeutic success. There is accumulating data that OVs are capable of dramatically altering the TME immune landscape, leading to improved antitumor activity alone or in combination with assorted immune modulators...
April 23, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29705790/immunotherapy-of-hepatocellular-carcinoma
#8
Bernd Heinrich, Carolin Czauderna, Jens U Marquardt
Hepatocellular carcinoma (HCC) is one of the most deadly and rapidly evolving cancers worldwide. The current systemic treatment strategies in advanced tumor stages remain limited despite promising preclinical and early-phase clinical results for some compounds, highlighting an unmet clinical need. Since the majority of HCCs evolve in the background of a chronic inflammatory liver damage, HCCs can be considered a paradigm for inflammation-induced cancers, which renders immunotherapeutic strategies particularly promising for this tumor entity...
2018: Oncology Research and Treatment
https://www.readbyqxmd.com/read/29705786/immunotherapy-of-esophageal-cancer-current-status-many-trials-and-innovative-strategies
#9
Maria Alsina, Markus Moehler, Sylvie Lorenzen
The majority of patients with esophageal cancer present with advanced disease and chemotherapy is the mainstay of palliation. However, efficacy is limited by the development of chemotherapy resistance and treatment options beyond first- and second-line treatment are scarce. Immunotherapy is a novel treatment option that has shown encouraging efficacy in several types of cancer, also in esophageal cancer. In esophageal squamous cell cancer (ESCC), early phase evaluation of immune checkpoint inhibitors has yielded promising results, however, results from phase 3 trials are currently still lacking...
2018: Oncology Research and Treatment
https://www.readbyqxmd.com/read/29695749/oncolytic-viruses-as-engineering-platforms-for-combination-immunotherapy
#10
REVIEW
Kwame Twumasi-Boateng, Jessica L Pettigrew, Y Y Eunice Kwok, John C Bell, Brad H Nelson
To effectively build on the recent successes of immune checkpoint blockade, adoptive T cell therapy and cancer vaccines, it is critical to rationally design combination strategies that will increase and extend efficacy to a larger proportion of patients. For example, the combination of anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and anti-programmed cell death protein 1 (PD1) immune checkpoint inhibitors essentially doubles the response rate in certain patients with metastatic melanoma. However, given the heterogeneity of cancer, it seems likely that even more complex combinations of immunomodulatory agents may be required to obtain consistent, durable therapeutic responses against a broad spectrum of cancers...
April 25, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29676175/epigenetic-agents-in-combined-anticancer-therapy
#11
Zdeněk Kejík, Milan Jakubek, Robert Kaplánek, Jarmila Králová, Ivan Mikula, Pavel Martásek, Vladimír Král
In the last decade, epigenetic drugs (such as inhibitors of DNA methyltransferases and histone deacetylases) have been intensively used for cancer treatment. Their applications have shown high anticancer effectivity and tolerable side effects. However, they are unfortunately not effective in the treatment of some types and phenotypes of cancers. Nevertheless, several studies have demonstrated that problems of drug efficacy can be overcome through the combined application of therapeutic modulates. Therefore, combined applications of epigenetic agents with chemotherapy, radiation therapy, immunotherapy, oncolytic virotherapy and hyperthermia have been presented...
April 20, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29628796/immunotherapy-of-melanoma
#12
Iwona Lugowska, Pawel Teterycz, Piotr Rutkowski
The immunotherapy is currently changing the landscape of oncology. Nowadays the standard of care in metastatic or unresectable melanoma patients include immunomodulating modalities such as anti-PD-1 drugs (nivolumab, pembrolizumab) and anti-CTLA-4 antibody ipilimumab. The improvements of progression free survival and overall survival connected with those treatments were unprecedented and have been confirmed in stage III trials. The efficacy of immunotherapy in metastatic setting can be further upgraded in some groups of patients by combining both types of antibodies...
March 2018: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/29588319/improving-car-t-cell-therapy-of-solid-tumors-with-oncolytic-virus-driven-production-of-a-bispecific-t-cell-engager
#13
Anna Wing, Carlos Alberto Fajardo, Avery D Posey, Carolyn Shaw, Tong Da, Regina Young, Ramon Alemany, Carl H June, Sonia Guedan
T cells expressing chimeric antigen receptors (CARTs) have shown significant promise in clinical trials to treat hematologic malignancies, but their efficacy in solid tumors has been limited. Oncolytic viruses have the potential to act in synergy with immunotherapies due to their immunogenic oncolytic properties and the opportunity of incorporating therapeutic transgenes in their genomes. Here, we hypothesized that an oncolytic adenovirus armed with an EGFR-targeting, bispecific T-cell engager (OAd-BiTE) would improve the outcome of CART-cell therapy in solid tumors...
March 27, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29564181/immunotherapy-in-pancreatic-adenocarcinoma-overcoming-barriers-to-response
#14
REVIEW
Ari Rosenberg, Devalingam Mahalingam
Pancreatic adenocarcinoma (PAC) remains one of the leading causes of cancer-related death. Despite multiple advances in targeted and immune therapies, the 5-year survival in advanced PAC remains poor. In this review, we discuss some of the unique aspects of the tumor microenvironment (TME) in PAC that may contribute to its resistance to immune therapies, as well as opportunities to potentially overcome some of these inherent barriers. Furthermore, we discuss strategies to enable immune therapies in PAC such as cytotoxic chemotherapy and radiation therapy, cancer vaccines, cytokine based therapy, oncolytic viruses, and adoptive T-cell therapy...
February 2018: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29561296/potential-clinical-and-immunotherapeutic-utility-of-talimogene-laherparepvec-for-patients-with-melanoma-after-disease-progression-on-immune-checkpoint-inhibitors-and-braf-inhibitors
#15
Jason Chesney, Yoannis Imbert-Fernandez, Sucheta Telang, Mary Baum, Smita Ranjan, Mostafa Fraig, Nicolas Batty
Talimogene laherparepvec is a genetically modified herpes simplex virus type 1-based oncolytic immunotherapy for the local treatment of unresectable subcutaneous and nodal tumors in patients with melanoma recurrent after initial surgery. We report on two patients with melanoma who, after progression on numerous systemic therapies, derived clinical benefit from talimogene laherparepvec in an expanded-access protocol (ClinicalTrials.gov, NCT02147951). Intralesional talimogene laherparepvec (day 1, ≤4 ml 10 PFU/ml; after 3 weeks, ≤4 ml 10 PFU/ml every 2 weeks) was administered until complete response, no injectable tumors, progressive disease, or intolerance occurred...
June 2018: Melanoma Research
https://www.readbyqxmd.com/read/29560124/cd30-targeted-oncolytic-viruses-as-novel-therapeutic-approach-against-classical-hodgkin-lymphoma
#16
Julia D S Hanauer, Benjamin Rengstl, Dina Kleinlützum, Johanna Reul, Anett Pfeiffer, Thorsten Friedel, Irene C Schneider, Sebastian Newrzela, Martin-Leo Hansmann, Christian J Buchholz, Alexander Muik
Classical Hodgkin lymphoma (cHL) is a hematopoietic malignancy with a characteristic cellular composition. The tumor mass is made up of infiltrated lymphocytes and other cells of hematologic origin but only very few neoplastic cells that are mainly identified by the diagnostic marker CD30. While most patients with early stage cHL can be cured by standard therapy, treatment options for relapsed or refractory cHL are still not sufficient, although immunotherapy-based approaches for the treatment of cHL patients have gained ground in the last decade...
February 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29557682/pharmacokinetic-drug-evaluation-of-talimogene-laherparepvec-for-the-treatment-of-advanced-melanoma
#17
REVIEW
Erin E Burke, Jonathan S Zager
Current treatment of advanced melanoma is rapidly changing with the introduction of new and effective therapies including systemic as well as locoregional therapies. An example of one such locoregional therapy is intralesional injection with talimogene laherparepvec (T-VEC). Areas covered: T-VEC has been shown in a number of studies to be an effective treatment for patients with stage IIIB, IIIC and IVM1a melanoma. In this article the effectiveness, pharmacokinetics and safety profile of T-VEC is reviewed. Additionally, new research looking at combinations of T-VEC and systemic immunotherapies is reviewed...
April 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29550660/oncolytic-viruses-and-immunity
#18
REVIEW
Shyambabu Chaurasiya, Nanhai G Chen, Yuman Fong
Initially, direct oncolysis was thought to be the sole mechanism through which oncolytic viruses (OVs) exert their anti-tumor effect, and the immune system was perceived as the major obstacle in oncolytic virotherapy. Over the last decade, there has been a lot of debate on whether the immune system is a friend or foe of OVs. However, we are now at a stage where the initial thinking has been reversed as a result of compelling evidence that the immune system plays a critical role in the success of oncolytic virotherapy...
April 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29504948/pd-l1-in-tumor-microenvironment-mediates-resistance-to-oncolytic-immunotherapy
#19
Dmitriy Zamarin, Jacob M Ricca, Svetlana Sadekova, Anton Oseledchyk, Ying Yu, Wendy M Blumenschein, Jerelyn Wong, Mathieu Gigoux, Taha Merghoub, Jedd D Wolchok
Intralesional therapy with oncolytic viruses (OVs) leads to the activation of local and systemic immune pathways, which may present targets for further combinatorial therapies. Here, we used human tumor histocultures as well as syngeneic tumor models treated with Newcastle disease virus (NDV) to identify a range of immune targets upregulated with OV treatment. Despite tumor infiltration of effector T lymphocytes in response to NDV, there was ongoing inhibition through programmed death ligand 1 (PD-L1), acting as a mechanism of early and late adaptive immune resistance to the type I IFN response and T cell infiltration, respectively...
April 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29504947/unleashing-the-therapeutic-potential-of-oncolytic-viruses
#20
Praveen K Bommareddy, Howard L Kaufman
Oncolytic viruses (OVs) are a versatile new class of therapeutic agents based on native or genetically modified viruses that selectively replicate in tumor cells and can express therapeutic transgenes designed to target cells within the tumor microenvironment and/or host immunity. To date, however, confirmation of the underlying mechanism of action and an understanding of innate and acquired drug resistance for most OVs have been limited. In this issue of the JCI, Zamarin et al. report a comprehensive analysis of an oncolytic Newcastle disease virus (NDV) using both murine melanoma tumor models and human tumor explants to explore how the virus promotes tumor eradication and details of the mechanisms involved...
April 2, 2018: Journal of Clinical Investigation
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