Home LiteratureArticle Details
PMID: 8956801 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Characterisation of immune responses in pancreatic carcinoma patients after mutant p21 ras peptide vaccination.

British journal of cancer ·Vol. 74 ·No. 11 ·1996-12-00 ·Pages 1828-33

Gjertsen MK, Saeterdal I, Thorsby E, Gaudernack G

Abstract

This is a study of immune responses generated by mutant ras peptide vaccination of patients with pancreatic adenocarcinoma. Responding T cells from one patient were cloned and two CD4+ T-lymphocyte clones (TLC) specific for the 12 Val peptide and restricted by HLA-DR6 or DQ2 were obtained. These class II molecules have not previously been found to bind or present mutant ras peptides to T cells. The DR6-restricted TLC showed marked cytotoxicity against autologous target cells pulsed with the 12 Val peptide. Target cells pulsed with the control peptide were not killed. Responding T cells from another patient showed cross-reactivity towards the homologous ras peptides. Investigation by limiting dilution analysis (LDA) revealed different T-cell precursor frequencies for the immunising, mutant ras peptide (1:28000), compared with the normal ras peptide (1:110000).

MeSH Terms
B-Lymphocytes/immunology,virology CD4-Positive T-Lymphocytes/immunology Cell Line, Transformed Cross Reactions/immunology Herpesvirus 4, Human Humans Immunity, Cellular Male Middle Aged Oncogene Protein p21(ras)/genetics,immunology Pancreatic Neoplasms/genetics,immunology Vaccination
Chemicals
Oncogene Protein p21(ras)
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Gjertsen M K
Institute of Transplantation Immunology, National Hospital, University of Oslo, Norway.
Saeterdal I
Thorsby E
Gaudernack G
References (25)
25 references, click to expand
  1. Biological properties of human c-Ha-ras1 genes mutated at codon 12.
    Nature. 1984 Nov 1-7;312(5989):71-5 PMID: 6092966
  2. T cell growth factor: parameters of production and a quantitative microassay for activity.
    J Immunol. 1978 Jun;120(6):2027-32 PMID: 307029
  3. Frequency of human alloantigen-reactive T lymphocytes. II. Method for limiting dilution analysis of alloantigen-reactive helper T cells in human peripheral blood.
    Transplantation. 1987 May;43(5):718-24 PMID: 2953094
  4. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes.
    Cell. 1988 May 20;53(4):549-54 PMID: 2453289
  5. Rapid immunomagnetic phenotyping of cells.
    J Immunogenet. 1989 Apr;16(2):169-75 PMID: 2687387
  6. Human T lymphocytes recognize a peptide of single point-mutated, oncogenic ras proteins.
    J Exp Med. 1991 Jan 1;173(1):273-6 PMID: 1670640
  7. Rapid and sensitive nonradioactive detection of mutant K-ras genes via 'enriched' PCR amplification.
    Oncogene. 1991 Jun;6(6):1079-83 PMID: 1676837
  8. Frequency and spectrum of mutations at codons 12 and 13 of the c-K-ras gene in human tumors.
    Environ Health Perspect. 1991 Jun;93:125-31 PMID: 1685441
  9. T-cell responses against products of oncogenes: generation and characterization of human T-cell clones specific for p21 ras-derived synthetic peptides.
    Hum Immunol. 1992 Apr;33(4):266-74 PMID: 1639630
  10. Memory T cells of a patient with follicular thyroid carcinoma recognize peptides derived from mutated p21 ras (Gln-->Leu61).
    Int Immunol. 1992 Nov;4(11):1331-7 PMID: 1282032
  11. T cell clones specific for p21 ras-derived peptides: characterization of their fine specificity and HLA restriction.
    Eur J Immunol. 1993 Mar;23(3):754-60 PMID: 8449222
  12. Identification of two cytotoxic T lymphocyte-recognized epitopes in the Ras protein.
    J Exp Med. 1993 May 1;177(5):1493-8 PMID: 7683038
  13. Overlapping epitopes encompassing a point mutation (12 Gly-->Arg) in p21 ras can be recognized by HLA-DR, -DP and -DQ restricted T cells.
    Eur J Immunol. 1993 Oct;23(10):2687-91 PMID: 7691613
  14. p21-ras-peptide-specific T-cell responses in a patient with colorectal cancer. CD4+ and CD8+ T cells recognize a peptide corresponding to a common mutation (13Gly-->Asp).
    Int J Cancer. 1994 Jan 2;56(1):40-5 PMID: 7903287
  15. T cell epitopes encompassing the mutational hot spot position 61 of p21 ras. Promiscuity in ras peptide binding to HLA.
    Eur J Immunol. 1994 Feb;24(2):410-4 PMID: 7507844
  16. Binding of ras oncogene peptides to purified HLA-DQ(alpha 1*0102,beta 1*0602) and -DR(alpha,beta 1*0101) molecules.
    Scand J Immunol. 1994 Jun;39(6):607-12 PMID: 8009176
  17. Tumor antigens recognized by T lymphocytes.
    Annu Rev Immunol. 1994;12:337-65 PMID: 8011285
  18. CD8+ T cells from a patient with colon carcinoma, specific for a mutant p21-Ras-derived peptide (Gly13-->Asp), are cytotoxic towards a carcinoma cell line harbouring the same mutation.
    Cancer Immunol Immunother. 1995 Mar;40(3):165-72 PMID: 7728775
  19. Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells.
    Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):8078-82 PMID: 7644541
  20. Vaccination with mutant ras peptides and induction of T-cell responsiveness in pancreatic carcinoma patients carrying the corresponding RAS mutation.
    Lancet. 1995 Nov 25;346(8987):1399-400 PMID: 7475823
  21. Ex vivo ras peptide vaccination in patients with advanced pancreatic cancer: results of a phase I/II study.
    Int J Cancer. 1996 Feb 8;65(4):450-3 PMID: 8621226
  22. Biological and biochemical properties of human rasH genes mutated at codon 61.
    Cell. 1986 Jan 17;44(1):167-76 PMID: 3510078
  23. Expression of cellular oncogenes in human malignancies.
    Science. 1984 Apr 20;224(4646):256-62 PMID: 6538699
  24. Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis.
    J Immunol. 1981 Apr;126(4):1614-9 PMID: 7009746
  25. Elevated expression of the human ras oncogene family in premalignant and malignant tumours of the colorectum.
    Br J Cancer. 1984 Jun;49(6):681-8 PMID: 6733017
Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
Published
1996-12-00
Pages
1828-33
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2077214
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com