In situadenovirus vaccination engages T effector cells against cancer

• Published in: Vaccine Vol. 27; no. 31; p. 4225
• Main Authors: Tuve, Sebastian, Liu, Ying, Tragoolpua, Khajornsak, Jacobs, Jeffrey Daniel, Yumul, Roma Christine, Li, Zong-Yi, Strauss, Robert, Hellström, Karl-Erik, Disis, Mary Lenora, Roffler, Steve, Lieber, André
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Limited 24.06.2009
• Subjects: Adenoviruses; Cancer; Clinical trials; Cytotoxicity; Genomes; Immune system; Infections; Laboratories; Lymphocytes; Medical research; Rodents; Studies; Tumors; Viral infections
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2009.03.074

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.