title: Recombinant Salmonella-based CEACAM6 and 4-1BBL vaccine enhances T-cell immunity and inhibits the development of colorectal cancer in rats: In vivo effects of vaccine containing 4-1BBL and CEACAM6.
abstract: The present study aimed to determine the effect of recombinant Salmonella (SL3261)-based CEACAM6 and 4-1BB ligand (4-1BBL) vaccine on the development of colorectal cancer in rats and the potential immune mechanisms involved. Attenuated Salmonella typhimurium (vaccine strain)‑carrying plasmids pIRES-CEACAM6, pIRES‑4‑1BBL and pIRES-CEACAM6-4-1BBL were constructed. The rats were administered subcutaneous injections of 1,2-dimethyl-hydrazine (DMH) once a week for 18 weeks. Eight weeks after the first injection, the rats were divided into the pIRES/SL3261, pIRES-4-1BBL/SL3261, pIRES-CEACAM6/SL3261 and pIRES-CEACAM6-4-1BBL/SL3261 groups, and fed with corresponding vaccine strains. The rats were then sacrificed, the number of colon tumors were recorded, and the Dukes' stage were evaluated. CD3, CD4, CD8, CD56, FOXP3 and CEACAM6 expression in tumor tissues was determined by immunohistochemical staining. Compared with the expression levels in the pIRES/SL3261 group, similar levels of CD3+, CD8+ and CD56+ expression were identified for the pIRES-CEACAM6/SL3261 group of rats. Additionally, a comparable number of tumors was detected in the pIRES-4-1BBL/SL3261 and pIRES-CEACAM6/SL3261 groups. By contrast, a significantly fewer number of tumors, albeit with a higher density of CD3+CD8+, CD56+ and a lower density of Foxp3+ tumor-infiltrating lymphocyte (TIL) cells was detected in the pIRES-CEACAM6-4-1BBL/SL3261 group of rats. The results indicated that vaccination with recombinant attenuated Salmonella harboring the CEACAM6 and 4-1BBL gene efficiently increased the number of CD3+CD8+ TIL and NK cells, decreased the number of FOXP3 cells and inhibited the development of DMH-induced colorectal cancer in rats.
authors: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Chunhui
authors: C
authors: Jin
authors: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Yingying
authors: Y
authors: Liu
authors: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Jianhong
authors: J
authors: Zhu
authors: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Tingting
authors: T
authors: Xia
authors: Department of Oncology, Wuxi Hospital of TCM, Wuxi, Jiangsu 214000, P.R. China.
authors: Baonan
authors: B
authors: Zhang
authors: Department of Pathology, Wuxi Hospital of TCM, Wuxi, Jiangsu 214000, P.R. China.
authors: Yajun
authors: Y
authors: Fei
authors: Department of Surgery, Huzhou Center Hospital, Huzhou, Zhejiang 313000, P.R. China.
authors: Bo
authors: B
authors: Ma
authors: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Jianxin
authors: J
authors: Ye
authors: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Weichang
authors: W
authors: Chen
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D053330:4-1BB Ligand / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D058851:GPI-Linked Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D053330:4-1BB Ligand; D015703:Antigens, CD; C504117:CEACAM6 protein, human; D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated; D019813:1,2-Dimethylhydrazine