Vaccination with metastasis-related tumor associated antigen TPD52 and CpG/ODN induces protective tumor immunity |
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Authors: | Laura A. Payton Jennifer D. Lewis Jennifer A. Byrne Robert K. Bright |
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Affiliation: | (1) Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, 3601 4th Street, MS 6591, Lubbock, TX 79430, USA;(2) Discipline of Paediatrics and Child Health, Childrens Hospital at Westmead, The University of Sydney, Sydney, NSW, Australia;(3) Present address: Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA |
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Abstract: | 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. |
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Keywords: | Vaccine Metastasis mD52 TPD52 Murine CpG |
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