p53 mutations are frequently found in human cancers and are often associated with the overexpression of wild-type (WT) protein or peptide sequences, supporting the notion that WT p53 epitopes may serve as potential targets for tumor immunotherapy. We have developed a cytotoxic T lymphocyte (CTL)/p53 tumor-associated antigen (TAA) model, based on immune recognition of a WT p53 determinant. WT p53-peptide-specific, major histocompatibility complex (MHC) classI-restricted CTL were produced from immunocompetent C57BL/6 (H-2b) mice after immunization with a previously defined WT p53 peptide (p53(232-240)) Epitope-specific CTL were then employed to identify syngeneic tumor cell populations expressing that antigenic determinant. Two syngeneic tumor cell lines, MC38 colon carcinoma and MC57G fibrosarcoma, were demonstrated to express the endogenous WT p53(232-240) determinant naturally, as defined by CD8 + CTL recognition. Cold-target inhibition assays confirmed that CTL-mediated lysis was due to immune recognition of the p53(232-240) peptide epitope. The p53(232-240)-specific CTL line did not lyse syngeneic normal cells (i.e., mitogen-activated splenocytes) in the absence of exogenous peptide, suggesting that the WT-p53-specific CTL could distinguish between tumor cells expressing self-TAA and normal host cells. We have demonstrated, for the first time, that the adoptive transfer of WT-p53-specific CTL to mice with established pulmonary metastasis resulted in antitumor activity in vivo. The ability to generate MHC-class-I-restricted CD8- CTL lines specific for a non-mutated p53 determinant from normal, immunocompetent mice, which display antitumor activity both in vitro and in vivo (by adoptive transfer), may have implications for the immunotherapy of certain p53-expressing malignancies.
{"title":"Characterization of CD8+ cytotoxic T lymphocyte/tumor cell interactions reflecting recognition of an endogenously expressed murine wild-type p53 determinant.","authors":"M Hilburger Ryan, S I Abrams","doi":"10.1007/s002620000156","DOIUrl":"10.1007/s002620000156","url":null,"abstract":"<p><p>p53 mutations are frequently found in human cancers and are often associated with the overexpression of wild-type (WT) protein or peptide sequences, supporting the notion that WT p53 epitopes may serve as potential targets for tumor immunotherapy. We have developed a cytotoxic T lymphocyte (CTL)/p53 tumor-associated antigen (TAA) model, based on immune recognition of a WT p53 determinant. WT p53-peptide-specific, major histocompatibility complex (MHC) classI-restricted CTL were produced from immunocompetent C57BL/6 (H-2b) mice after immunization with a previously defined WT p53 peptide (p53(232-240)) Epitope-specific CTL were then employed to identify syngeneic tumor cell populations expressing that antigenic determinant. Two syngeneic tumor cell lines, MC38 colon carcinoma and MC57G fibrosarcoma, were demonstrated to express the endogenous WT p53(232-240) determinant naturally, as defined by CD8 + CTL recognition. Cold-target inhibition assays confirmed that CTL-mediated lysis was due to immune recognition of the p53(232-240) peptide epitope. The p53(232-240)-specific CTL line did not lyse syngeneic normal cells (i.e., mitogen-activated splenocytes) in the absence of exogenous peptide, suggesting that the WT-p53-specific CTL could distinguish between tumor cells expressing self-TAA and normal host cells. We have demonstrated, for the first time, that the adoptive transfer of WT-p53-specific CTL to mice with established pulmonary metastasis resulted in antitumor activity in vivo. The ability to generate MHC-class-I-restricted CD8- CTL lines specific for a non-mutated p53 determinant from normal, immunocompetent mice, which display antitumor activity both in vitro and in vivo (by adoptive transfer), may have implications for the immunotherapy of certain p53-expressing malignancies.</p>","PeriodicalId":78649,"journal":{"name":"Revue francaise d'etudes cliniques et biologiques","volume":"14 10 1","pages":"603-12"},"PeriodicalIF":5.8,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11036958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82920932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Australia antigen and viral hepatitis.","authors":"W T London, I Millman","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":78649,"journal":{"name":"Revue francaise d'etudes cliniques et biologiques","volume":"14 10","pages":"961-3"},"PeriodicalIF":0.0,"publicationDate":"1969-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"15350044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Immune reactions in leukemic or preleukemic AkR mice].","authors":"J F Doré, M Schneider, G Mathé","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":78649,"journal":{"name":"Revue francaise d'etudes cliniques et biologiques","volume":"14 10","pages":"1003-7"},"PeriodicalIF":0.0,"publicationDate":"1969-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"16460127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Study of chronic potassium deficiency in man. I. Influence of rapid changes in blood potassium on urinary potassium output].","authors":"B Antoine, D Patte","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":78649,"journal":{"name":"Revue francaise d'etudes cliniques et biologiques","volume":"14 10","pages":"984-94"},"PeriodicalIF":0.0,"publicationDate":"1969-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"16460134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[2 cases of myeloma with monoclonal IgD immunoglobulin].","authors":"J M Fine","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":78649,"journal":{"name":"Revue francaise d'etudes cliniques et biologiques","volume":"14 10","pages":"1018-24"},"PeriodicalIF":0.0,"publicationDate":"1969-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"15298454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[The biological bases of the detection of malignant tumors by selective fixation of radioactive indicators].","authors":"R Plagne, G Meyniel","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":78649,"journal":{"name":"Revue francaise d'etudes cliniques et biologiques","volume":"14 10","pages":"1036-53"},"PeriodicalIF":0.0,"publicationDate":"1969-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"16001353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Koltay, I Virág, L Réthy, M Illyés, K Streitmann
{"title":"Immunological response to sheep red blood cells of mice treated with heterologous antilymphocyte serum in the neonatal period.","authors":"M Koltay, I Virág, L Réthy, M Illyés, K Streitmann","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":78649,"journal":{"name":"Revue francaise d'etudes cliniques et biologiques","volume":"14 10","pages":"1032-5"},"PeriodicalIF":0.0,"publicationDate":"1969-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"16460132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Isolation of IgG immunoglobulin from human plasma using caprylic acid].","authors":"M Steinbuch, R Audran","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":78649,"journal":{"name":"Revue francaise d'etudes cliniques et biologiques","volume":"14 10","pages":"1054-8"},"PeriodicalIF":0.0,"publicationDate":"1969-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"16460133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Study of urinary pepsinogen and its correlations with gastric proteolytic secretion].","authors":"H Hirsch-Marie, M Conte","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":78649,"journal":{"name":"Revue francaise d'etudes cliniques et biologiques","volume":"14 10","pages":"977-83"},"PeriodicalIF":0.0,"publicationDate":"1969-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"16001355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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