PMID: 9524714Apr 3, 1998Paper

An HLA-restricted, p53 specific immune response from HLA transgenic p53 knockout mice

Annals of Surgical Oncology
T M McCartyJoshua D I Ellenhorn

Abstract

p53 is over-expressed in most human malignancies and is therefore an attractive target for immunotherapy. Unfortunately, a human cytotoxic T cell response to p53 is difficult to generate. p53 knockout transgenic mice may provide a model to circumvent immunologic tolerance to p53 and develop high-affinity p53-specific cytotoxic T lymphocytes (CTL). p53 knockout, HLA A2.1 transgenic mice were generated and immunized with the immunodominant wild-type p53 nonamer peptide epitope p53149-157. Two weeks later splenocytes were harvested and stimulated in vitro with acid-treated, p53 peptide-pulsed syngeneic blast cells. Cultures were restimulated weekly with acid-treated, p53 peptide-pulsed Jurkat cells transfected with the HLA A2.1 gene. Peptide-specific cytotoxic activity was measured by chromium release assay, and the resulting CD8+ effectors were cloned via limiting dilution. P53 peptide-specific CTL were generated against p53149-157. Clones generated from the p53149-157 cell line demonstrated high affinity and specificity for p53149-157 when presented by HLA A2.1+ antigen-presenting cells. The p53149-157 CTL killed only cells overexpressing p53 cells that were HLA A2.1+ and did not kill cells with normal levels of p53 expression o...Continue Reading

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Citations

Apr 25, 2008·Current Protocols in Immunology·Malaya Bhattacharya-ChatterjeeSunil K Chatterjee
Mar 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jonathan EspenschiedJoshua D I Ellenhorn
Jun 26, 2010·Cancer Immunology, Immunotherapy : CII·Pedro A Andrade FilhoRobert L Ferris
Sep 10, 2019·World Journal of Gastroenterology : WJG·Kheng-Seong NgPeter Michael Sagar
Oct 2, 2001·Critical Reviews in Oncology/hematology·P M McLaughlinL F de Leij

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