The rationale of vectored gene-fusion vaccines against cancer: evolving strategies and latest evidence.

Abstract

The development of vaccines that target tumor antigens in cancer has proven difficult. A major reason for this is that T cells specific for tumor self-antigens and neoantigens are eliminated or inactivated through mechanisms of tolerance. Antigen fusion strategies which increase the ability of vaccines to stimulate T cells that have escaped tolerance mechanisms, may have a particular potential as immunotherapies. This review highlights antigen fusion strategies that have been successful in stimulating the induction of T-cell immunity against cancer and counteracting tumor-associated tolerance. In preclinical studies, these strategies have shown to improve the potency of vectored vaccines through fusion of tumor antigen to proteins or protein domains that increase CD4+ T-cell help, CD8+ T-cell responses or both the CD4+ and CD8+ T-cell responses. However, in clinical trials such strategies seem to be less efficient when provided as a DNA vaccine. The first clinical trial using a viral vectored fusion-gene vaccine is expected to be tested as a partner in a heterologous prime-boost regimen directed against cervical cancer.

• Authors: Emeline Ragonnaud, Peter Holst
• Journal: Therapeutic advances in vaccines (Ther Adv Vaccines) Vol. 1 Issue 1 Pg. 33-47 (May 2013) ISSN: 2051-0136 [Print] England
• PMID: 24757514 (Publication Type: Journal Article)