title: Wildtype p53-specific antibody and T-cell responses in cancer patients.
abstract: Mutation in the p53 gene based on single amino acid substitutions is a frequent event in human cancer. Accumulated mutant p53 protein is released to antigen presenting cells of the immune system and anti-p53 immune responses even against wt p53 is induced and observed in a number of human cancer patients. Detection of antibodies against wt p53 protein has been used as a diagnostic and prognostic marker and discovery of new T-cell epitopes has enabled design of cancer vaccination protocols with promising results. Here, we identified wt p53-specific antibodies in various cancer patients and identified a broad range of responses against wt p53 protein and 15-mer peptides using a novel print array technology. Likewise, using bioinformatic tools in silico, we identified CD8 T-cell specificity or reactivity against HLA-A*02:01 binding peptides wt p53(65-73), wt p53(187-197), and wt p53(264-272) in breast cancer patients and against HLA-A*01:01 binding peptide wt p53(226-234) and HLA-B*07:02 binding peptide wt p53(74-82) in renal cell cancer and breast cancer patients, respectively. Finally, we analyzed antibody and T-cell responses against wt p53 15-mer peptides in patients with metastatic renal cell carcinoma who were alive with no evidence of disease after a follow-up period of minimum 5 years after treatment with IL-2 ± IFN-α ± histamine containing immunotherapy to identify novel epitopes for use in immunotherapy and for potential response biomarkers. However, none of the wt p53 reactivity observed justified use of 15-mer or was related to survival in this rare patient population.
authors: Department of International Health, Immunology and Microbiology, The Panum Institute, University of Copenhagen, Denmark. elmpedersen@sund.ku.dk
authors: Anders Elm
authors: AE
authors: Pedersen
authors: Anette
authors: A
authors: Stryhn
authors: Sune
authors: S
authors: Justesen
authors: Mikkel
authors: M
authors: Harndahl
authors: Susanne
authors: S
authors: Rasmussen
authors: Frede
authors: F
authors: Donskov
authors: Mogens H
authors: MH
authors: Claesson
authors: Johannes W
authors: JW
authors: Pedersen
authors: Hans H
authors: HH
authors: Wandall
authors: Inge Marie
authors: IM
authors: Svane
authors: Søren
authors: S
authors: Buus
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000097:blood; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019496:Cancer Vaccines; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D005260:Female; D015234:HLA-A Antigens / Q000378:metabolism; D006801:Humans; D016233:Immunotherapy, Active; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000906:Antibodies; D054316:Biomarkers, Pharmacological; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53