In situadenovirus vaccination engages T effector cells against cancer
The efficacy of cancer immunotherapy is limited because of central and peripheral immune tolerance towards tumor-antigens. We propose a novel approach based on the fact that the immune system has not evolved tolerance towards adenoviruses (Ads) and that Ads have not evolved efficient mechanisms for...
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Published in | Vaccine Vol. 27; no. 31; p. 4225 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Kidlington
Elsevier Limited
24.06.2009
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Subjects | |
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Abstract | The efficacy of cancer immunotherapy is limited because of central and peripheral immune tolerance towards tumor-antigens. We propose a novel approach based on the fact that the immune system has not evolved tolerance towards adenoviruses (Ads) and that Ads have not evolved efficient mechanisms for immune-escape. The host-response to intratumoral Ad-vector injection in mice that were immunologically tolerant toneu-positive syngeneic mammary-cancer (MMC) was investigated. Intratumoral injection with replication-deficient, transgene-devoid Ad induced immune responses at two different anatomical sites: the tumor-draining lymph nodes and the tumor microenvironment. The lymph nodes supported the generation of bothneu- and Ad-specific T effector cells, while inside the tumor microenvironment only Ad-specific T cells expanded. Importantly, Ad-specific T cells were anti-tumor-reactive despite the presence of active regulatory T cell-mediated immune tolerance inside MMC tumors and anti-tumor efficacy of Ad was increased by pre-immunization against Ad despite the production of Ad-neutralizing antibodies. |
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AbstractList | The efficacy of cancer immunotherapy is limited because of central and peripheral immune tolerance towards tumor-antigens. We propose a novel approach based on the fact that the immune system has not evolved tolerance towards adenoviruses (Ads) and that Ads have not evolved efficient mechanisms for immune-escape. The host-response to intratumoral Ad-vector injection in mice that were immunologically tolerant toneu-positive syngeneic mammary-cancer (MMC) was investigated. Intratumoral injection with replication-deficient, transgene-devoid Ad induced immune responses at two different anatomical sites: the tumor-draining lymph nodes and the tumor microenvironment. The lymph nodes supported the generation of bothneu- and Ad-specific T effector cells, while inside the tumor microenvironment only Ad-specific T cells expanded. Importantly, Ad-specific T cells were anti-tumor-reactive despite the presence of active regulatory T cell-mediated immune tolerance inside MMC tumors and anti-tumor efficacy of Ad was increased by pre-immunization against Ad despite the production of Ad-neutralizing antibodies. |
Author | Jacobs, Jeffrey Daniel Hellström, Karl-Erik Liu, Ying Strauss, Robert Lieber, André Yumul, Roma Christine Tragoolpua, Khajornsak Li, Zong-Yi Roffler, Steve Tuve, Sebastian Disis, Mary Lenora |
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Copyright | Copyright Elsevier Limited Jun 24, 2009 |
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DOI | 10.1016/j.vaccine.2009.03.074 |
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SubjectTerms | Adenoviruses Cancer Clinical trials Cytotoxicity Genomes Immune system Infections Laboratories Lymphocytes Medical research Rodents Studies Tumors Viral infections |
Title | In situadenovirus vaccination engages T effector cells against cancer |
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