Vaccination with metastasis-related tumor associated antigen TPD52 and CpG/ODN induces protective tumor immunity.
Tumor protein D52 (TPD52) is involved in transformation and metastasis and has been shown to be over-expressed in tumor cells compared to normal cells and tissues. Murine TPD52 (mD52) shares 86% protein identity with the human TPD52 orthologue (hD52). To study TPD52 protein as a target for active vaccination recombinant, mD52 was administered as a protein-based vaccine. Naïve mice were immunized with either mD52 protein and CpG/ODN as a molecular adjuvant or CpG/ODN alone. Two weeks following the final immunization, mice were challenged s.c. with syngeneic tumor cells that over-express mD52. Two distinct murine tumor cell lines were used for challenge in this model, mKSA and 3T3.mD52. Half of the mice immunized with mD52 and CpG/ODN rejected or delayed onset of mKSA s.c. tumor cell growth, and 40% of mice challenged with 3T3.mD52 rejected s.c. tumor growth, as well as the formation of spontaneous lethal lung metastases. Mice immunized with mD52 and CpG/ODN generated detectable mD52-specific IgG antibody responses indicating that mD52 protein vaccination induced an adaptive immune response. In addition, mice that rejected tumor challenge generated tumor-specific cytotoxic T lymphocytes' responses. Importantly, microscopic and gross evaluation of organs from mD52 immunized mice revealed no evidence of autoimmunity as assessed by absence of T cell infiltration and absence of microscopic pathology. Together, these data demonstrate that mD52 vaccination induces an immune response that is capable of rejecting tumors that over-express mD52 without the induction of harmful autoimmunity.
Payton
Laura A
LA
Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, 3601 4th Street, MS 6591, Lubbock, TX 79430, USA.
Lewis
Jennifer D
JD
Byrne
Jennifer A
JA
Bright
Robert K
RK
D000818:Animals; D019496:Cancer Vaccines / Q000737:chemistry*; D045744:Cell Line, Tumor; D018899:CpG Islands; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009841:Oligonucleotides / Q000737:chemistry*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology
D019496:Cancer Vaccines; D007074:Immunoglobulin G; D009363:Neoplasm Proteins; D009841:Oligonucleotides; C114751:TPD52 protein, human