Therapeutic vaccine to control stromal tumor-induced immunosuppression in human uterine cervixc cancer.
Cancer cells may escape immune surveillance by secreting in their microenvironment soluble factors that may locally paralyze the stromal effector immune cells. In the human uterine cervix cancer, HPV-16 E7 protein, released in the stroma, should contribute to cancer cells immune escape since this protein inhibits the cellular immune response to recall antigens or alloantigens and strongly enhances the release of immunosuppressive cytokines by APCs. This prompted us to prepare a therapeutic vaccine triggering anti-E7 neutralizing Abs to antagonize the E7-induced stromal immunosuppressive effects and allow cellular immune reaction towards cancer cells including specific CTLs, induced by conventional vaccine, to be effective. Since HPV-16 is a mucosotropic virus, this therapeutic vaccine has been prepared to generate systemic as well as mucosal immunity.
Le Buanec
H
H
Laboratoire de Physiologie Cellulaire, Université Pierre et Marie Curie, 75015 Paris, France. lebuanec@ccr.jussieu.fr
Cohen
L
L
Paturance
S
S
Burny
A
A
Gallo
R C
RC
Zagury
D
D
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D002277:Carcinoma / Q000276:immunology / Q000628:therapy*; D002584:Cervix Uteri / Q000166:cytology / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D017154:Stromal Cells / Q000276:immunology*; D014121:Toxoids / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy*
D019496:Cancer Vaccines; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D014121:Toxoids; C059731:oncogene protein E7, Human papillomavirus type 16