Following infection with

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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 to neu-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 both neu- 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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