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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.

作者:Emeline, Ragonnaud;Peter, Holst

来源:Therapeutic advances in vaccines 2013 年 1卷 1期

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| 浏览:45
作者:
Emeline, Ragonnaud;Peter, Holst
来源:
Therapeutic advances in vaccines 2013 年 1卷 1期
标签:
Antigen engineering DNA vaccine breaking of tolerance cancer immunogenicity low avidity T cells viral vector vaccine
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.