An Experimental Vaccine Expressing Wild‐Type p53 Induces Protective Immunity against Glioblastoma Cells with High Levels of Endogenous p53

• Published in: Scandinavian journal of immunology 2002-10, Vol.56 (4), p.361-375
• Main Authors: BLASZCZYK‐THURIN, M., O, I., ERTL, H. C. J.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adjuvants, Immunologic; Animals; Cancer Vaccines - immunology; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Female; Gene Expression Regulation, Neoplastic; Genes, p53; Glioblastoma - immunology; Glioblastoma - metabolism; Glioblastoma - pathology; Glioblastoma - prevention & control; Hypersensitivity, Delayed - immunology; Interleukin-2 - administration & dosage; Killer Cells, Natural - immunology; Lymphocytes, Tumor-Infiltrating - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Recombinant Fusion Proteins - administration & dosage; Sarcoma, Experimental - metabolism; Sarcoma, Experimental - pathology; Tumor Cells, Cultured - transplantation; Tumor Suppressor Protein p53 - administration & dosage; Tumor Suppressor Protein p53 - biosynthesis; Tumor Suppressor Protein p53 - deficiency; Tumor Suppressor Protein p53 - immunology; Vaccination; Vaccines, Synthetic - immunology; Vaccinia virus - genetics
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1046/j.1365-3083.2002.01119.x

Inoculation of mice with a recombinant vaccinia virus expressing the full‐length mouse wild‐type p53 protein (Vp53‐wt) was shown to induce partial protection against peripheral challenge with a mouse glioblastoma cell line, termed GL261, expressing high levels of nuclear, endogenous wild‐type p53. In vivo experiments with knockout (KO) mice and mice treated with depleting doses of antibodies specific to lymphocyte subsets revealed that vaccine efficacy depended on CD4+ and CD8+ T cells as well as on natural killer (NK) cells. Vp53‐wt virus‐vaccinated mice that failed to develop tumours upon challenge with a minimal tumourigenic dose of GL261 cells remained completely resistant to further challenge with increased doses of GL261 cells. The efficacy of the Vp53‐wt vaccine was improved by adding recombinant mouse interleukin‐12 (rIL‐12) as an adjuvant at the time of tumour challenge. The induction of T cells to p53 in Vp53‐wt virus‐immune mice was also demonstrated at the tumour site by immunochemistry and was further confirmed by a delayed‐type hypersensitivity response to the p53 protein, although in vitro experiments using splenocytes from vaccinated mice failed to demonstrate CD4+ or CD8+ T‐cell activity to p53.