ONCOLYTIC VIROTHERAPY

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Oncolytic virotherapy is an emerging treatment modality which uses replication competent viruses to destroy cancers. Advances in the past two years include preclinical proof of feasibility for a single-shot virotherapy cure, identification of drugs that accelerate intratumoral virus propagation, new strategies to maximize the immunotherapeutic potential of oncolytic virotherapy, and clinical confirmation of a critical viremic thereshold for vascular delivery and intratumoral virus replication. The primary clinical milestone was completion of accrual in a phase III trial of intratumoral herpes simplex virus therapy using talimogene laherparepvec for metastatic melanoma. Challenges for the field are to select ‘winners’ from a burgeoning number of oncolytic platforms and engineered derivatives, to transiently suppress but then unleash the power of the immune system to maximize both virus spread and anticancer immunity, to develop more meaningful preclinical virotherapy models and to manufacture viruses with orders of magnitude higher yields compared to established vaccine manufacturing processes.

Related collections

Most cited references 157

Record: found
Abstract: found
Article: not found

A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs.

Y Matsumura, H. Maeda (1986)

We previously found that a polymer conjugated to the anticancer protein neocarzinostatin, named smancs, accumulated more in tumor tissues than did neocarzinostatin. To determine the general mechanism of this tumoritropic accumulation of smancs and other proteins, we used radioactive (51Cr-labeled) proteins of various molecular sizes (Mr 12,000 to 160,000) and other properties. In addition, we used dye-complexed serum albumin to visualize the accumulation in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of these mice, and a ratio of the protein concentration in the tumor to that in the blood of 5 was obtained within 19 to 72 h. A large protein like immunoglobulin G required a longer time to reach this value of 5. The protein concentration ratio in the tumor to that in the blood of neither 1 nor 5 was achieved with neocarzinostatin, a representative of a small protein (Mr 12,000) in all time. We speculate that the tumoritropic accumulation of these proteins resulted because of the hypervasculature, an enhanced permeability to even macromolecules, and little recovery through either blood vessels or lymphatic vessels. This accumulation of macromolecules in the tumor was also found after i.v. injection of an albumin-dye complex (Mr 69,000), as well as after injection into normal and tumor tissues. The complex was retained only by tumor tissue for prolonged periods. There was little lymphatic recovery of macromolecules from tumor tissue. The present finding is of potential value in macromolecular tumor therapeutics and diagnosis.

0 comments Cited 1010 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Polymer conjugates as anticancer nanomedicines.

Ruth Duncan (2006)

The transfer of polymer-protein conjugates into routine clinical use, and the clinical development of polymer-anticancer-drug conjugates, both as single agents and as components of combination therapy, is establishing polymer therapeutics as one of the first classes of anticancer nanomedicines. There is growing optimism that ever more sophisticated polymer-based vectors will be a significant addition to the armoury currently used for cancer therapy.

0 comments Cited 371 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression.

Li Yang, Yanli Pang, Harold L. Moses (2010)

Transforming growth factor beta (TGF-beta) plays an important role in tumor initiation and progression, functioning as both a suppressor and a promoter. The mechanisms underlying this dual role of TGF-beta remain unclear. TGF-beta exerts systemic immune suppression and inhibits host immunosurveillance. Neutralizing TGF-beta enhances CD8+ T-cell- and NK-cell-mediated anti-tumor immune responses. It also increases neutrophil-attracting chemokines resulting in recruitment and activation of neutrophils with an antitumor phenotype. In addition to its systemic effects, TGF-beta regulates infiltration of inflammatory/immune cells and cancer-associated fibroblasts in the tumor microenvironment causing direct changes in tumor cells. Understanding TGF-beta regulation at the interface of tumor and host immunity should provide insights into developing effective TGF-beta antagonists and biomarkers for patient selection and efficacy of TGF-beta antagonist treatment. Published by Elsevier Ltd.

0 comments Cited 337 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-journal-id): 9604648

Journal ID (pubmed-jr-id): 20305

Journal ID (nlm-ta): Nat Biotechnol

Journal ID (iso-abbrev): Nat. Biotechnol.

Title: Nature biotechnology

ISSN (Print): 1087-0156

ISSN (Electronic): 1546-1696

Publication date Nihms-submitted: 23 December 2013

Publication date (Electronic): 10 July 2012

Publication date PMC-release: 10 January 2014

Volume: 30

Issue: 7

Electronic Location Identifier: 10.1038/nbt.2287

Affiliations

[1 ]Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA

[2 ]Center for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

Article

Manuscript ID: NIHMS381382

DOI: 10.1038/nbt.2287

PMC ID: 3888062

PubMed ID: 22781695

SO-VID: b415c4bf-88bb-4259-8f01-17fd0630cfe9

License:

Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms