In situ adenovirus 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 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.
Tuve
Sebastian
S
Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Liu
Ying
Y
Tragoolpua
Khajornsak
K
Jacobs
Jeffrey Daniel
JD
Yumul
Roma Christine
RC
Li
Zong-Yi
ZY
Strauss
Robert
R
Hellström
Karl-Erik
KE
Disis
Mary Lenora
ML
Roffler
Steve
S
Lieber
André
A
D000256:Adenoviridae / Q000276:immunology*; D000818:Animals; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000628:therapy*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D014765:Viral Vaccines