title: Intrarectal vaccination with recombinant vaccinia virus expressing carcinoembronic antigen induces mucosal and systemic immunity and prevents progression of colorectal cancer.
abstract: The gastrointestinal mucosa contains an intact immune system that protects the host from pathogens and communicates with the systemic immune system. Absorptive epithelial cells in the mucosa give rise to malignant tumors although the interaction between tumor cells and the mucosal immune system is not well defined. The pathophysiology of colorectal cancer has been elucidated through studies of hereditary syndromes, such as familial adenomatous polyposis, a cancer predisposition syndrome caused by germline mutations in the adenomatous polyposis coli tumor suppressor gene. Patients with FAP develop adenomas and inevitably progress to invasive carcinomas by the age of 40. To better delineate the role of mucosal immunity in colorectal cancer, we evaluated the efficacy of intrarectal recombinant vaccinia virus expressing the human carcinoembryonic Ag (CEA) in a murine FAP model in which mice are predisposed to colorectal cancer and also express human CEA in the gut. Mucosal vaccination reduced the incidence of spontaneous adenomas and completely prevented progression to invasive carcinoma. The therapeutic effects were associated with induction of mucosal CEA-specific IgA Ab titers and CD8(+) CTLs. Mucosal vaccination was also associated with an increase in systemic CEA-specific IgG Ab titers, CD4(+) and CD8(+) T cell responses and resulted in growth inhibition of s.c. implanted CEA-expressing tumors suggesting communication between mucosal and systemic immune compartments. Thus, intrarectal vaccination induces mucosal and systemic antitumor immunity and prevents progression of spontaneous colorectal cancer. These results have implications for the prevention of colorectal cancer in high-risk individuals.
authors.affiliation: Division of Surgical Oncology, The Tumor Immunology Laboratory, Columbia University, New York, NY 10032, USA.
authors.forename: Seunghee
authors.initials: S
authors.lastname: Kim-Schulze
authors.forename: Hong Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Alberto
authors.initials: A
authors.lastname: Wainstein
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Wein Cui
authors.initials: WC
authors.lastname: Yang
authors.forename: Dorota
authors.initials: D
authors.lastname: Moroziewicz
authors.forename: Phyllus Y
authors.initials: PY
authors.lastname: Mong
authors.forename: Michal
authors.initials: M
authors.lastname: Bereta
authors.forename: Bret
authors.initials: B
authors.lastname: Taback
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000276:immunology / Q000628:therapy; D000328:Adult; D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000628:therapy*; D005260:Female; D015870:Gene Expression; D006801:Humans; D018928:Immunity, Mucosal; D051379:Mice; D009361:Neoplasm Invasiveness; D014611:Vaccination; D014616:Vaccinia virus
chemical_list: D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen