IMR Press / FBL / Volume 13 / Issue 7 / DOI: 10.2741/2867

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Cancer therapy with local oncolysis and topical cytokine secretion
Show Less
1 Division of Pathology, Chiba Cancer Center Research Institute, Chiba, Japan
2 Department of Respirology, Graduate School of Medicine, Chiba University, Japan
3 Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, Japan
4 Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Japan
5 Center of Excellence (COE) Program in the 21st Century, Graduate School of Medicine, Chiba University, Japan

*Author to whom correspondence should be addressed.

Academic Editor: Masatoshi Tagawa

Front. Biosci. (Landmark Ed) 2008, 13(7), 2578–2587;
Published: 1 January 2008
(This article belongs to the Special Issue Current gene therapy for cancer)

Direct destruction of targeted tumors and subsequent induction of systemic immunity is not pertinent to gene therapy but gene therapy is probably the most suitable therapeutic modality to achieve the local and systemic anti-tumor effects. Current strategies for cancer gene therapy in fact consist of direct inhibition of tumor growth and activation of systemic host defense mechanisms. We have been working on development of oncolytic adenoviruses and cytokine-mediated activation of host immune systems to produce better therapeutic effects. The adenoviruses in which the E1A expression is controlled by an exogenous regulatory region are preferentially cytotoxic to target tumor cells depending on the specificity of the regulatory region and cytokines that differentiate naive T cells into T helper type 1 cells can amplify immune responses generated. Combination of the two strategies has an advantage. Tumor destruction by oncolytic viruses does not impair immune systems in contract to chemotherapy and radiotherapy but enable to produce anti-tumor responses against putative tumor antigens that are subsequently released from the destroyed tumor. In this process, dendritic cells play a pivotal role since they act as professional antigen presenting cells and are involved in an initial phase of immune responses, either activation of immunity or induction of immune tolerance. Antigen loading with subsequent appropriate activation of dendritic cells is thereby crucial for activated anti-tumor responses, which possibly eliminate even distant metastatic foci. Combinatory gene therapy with oncolytic viruses and activation of host immune system thereby can evoke immune responses against all the tumor antigens expressed by the process of "antigen-spreading" mechanisms.

Back to top