title: Pre-clinical toxicity and immunogenicity evaluation of a MUC1-MBP/BCG anti-tumor vaccine.
abstract: Mucin 1 (MUC1), as an oncogene, plays a key role in the progression and tumorigenesis of many human adenocarcinomas and is an attractive target in tumor immunotherapy. Our previous study showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific Th1-dominant immune response, simulated MUC1-specific cytotoxic T lymphocyte killing activity, and could significantly inhibit MUC1-expression B16 cells' growth in mice. To help move the vaccine into a Phase I clinical trial, in the current study, a pre-clinical toxicity and immunogenicity evaluation of the vaccine was conducted. The evaluation was comprised of a single-dose acute toxicity study in mice, repeat-dose chronic toxicity and immunogenicity studies in rats, and pilot toxicity and immunogenicity studies in cynomolgus monkeys. The results showed that treatment with the MUC1-MBP/BCG anti-tumor vaccine did not cause any organ toxicity, except for arthritis or local nodules induced by BCG in several rats. Furthermore, the vaccine significantly increased the levels of IFN-γ in rats, indicating that Th1 cells were activated. In addition, the results showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific IgG antibody response both in rats and cynomolgus monkeys. Collectively, these data are beneficial to move the MUC1-MBP/BCG anti-tumor vaccine into a Phase I clinical trial.
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun 130021, China; Department of Radiology, Japan Union Hospital of Jilin University, Jilin University, Changchun 130021, China.
authors.forename: Boqi
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun 130021, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun 130021, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun 130021, China.
authors.forename: Tanxiu
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun 130021, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Ni
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun 130021, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun 130021, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun 130021, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun 130021, China. Electronic address: taiguixiang@163.com.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Tai
mesh_terms: D000818:Animals; D001168:Arthritis / Q000209:etiology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D058619:Maltose-Binding Proteins / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D018396:Mucin-1 / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics; D009163:Mycobacterium bovis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018417:Th1 Cells / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D019496:Cancer Vaccines; D058619:Maltose-Binding Proteins; D018396:Mucin-1; D014614:Vaccines, Synthetic; D007371:Interferon-gamma
keywords: Anti-tumor; BCG; Immunogenicity; Mucin 1; Toxicity; Vaccine