Ovarian tumour reactive cytotoxic T lymphocytes can recognize peptide determinants on polymorphic epithelial mucins Muc-1

  • C. G. Ioannides
  • B. Fisk
  • K. R. Jerome
  • B. Chesak
  • T. Irimura
  • J. T. Wharton
  • O. J. Finn


Tumour reactive cytotoxic T lymphocytes (CTL) have been isolated and propagated in culture from tumour infiltrating lymphocytes (TIL) of various tumours [1–6]. The fact that these cells are endowed with the ability to lyse autologous tumour cells has lead to their use in cancer immunotherapy trials, with encouraging results in certain instances [1].


Ovarian Tumour Autologous Tumour Core Peptide CaOV3 Cell Lytic Unit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Topalian, S.L., Solomon, D., Avis, P.P. et al. (1988) Immunotherapy of patients with advanced cancer using tumour infiltrating lymphocytes and recombinant interleukin-2: a pilot study, J. Clin. Oncol, 6, 839–53.PubMedGoogle Scholar
  2. 2.
    Itoh, K., Platsoucas C.D. and Balch, C.M. (1988) Autologous tumour-specific cytotoxic T lymphocytes in the infiltrate of human metastatic melanomas, J. Exp. Med., 168, 1419–41.PubMedCrossRefGoogle Scholar
  3. 3.
    Heo, D.S., Whiteside, T.L., Kanbour, A. and Herberman, R.B. (1988) Lymphocytes infiltrating human ovarian tumours. I. Role of Leu-19 (NKHl)-positive recombinant IL-2 activated cultures of lymphocytes infiltrating human ovarian tumours. J. Immunol, 140, 4042–9.PubMedGoogle Scholar
  4. 4.
    Ioannides, C.G., Preedman, R.S., Platsoucas, C.D. et al. (1991) Cytotoxic T cell clones isolated from ovarian tumour infiltrating lymphocytes recognize multiple antigenic epitopes on autologous tumour cells, J. Immunol, 146,1700–7.PubMedGoogle Scholar
  5. 5.
    Vaccarello, L., Wang, Y. and Whiteside, T.L. (1986) Sustained outgrowth of autotumour- reactive T lymphocytes from human ovarian carcinomas in the presence of tumour necrosis factor α and IL-2.Hum. Immunol, 28, 216–27.CrossRefGoogle Scholar
  6. 6.
    Ioannides, C.G., Platsoucas, C.D., Rashed, S. et al. (1991) Tumour cytolysis by lymphocytes infiltrating ovarian malignant ascites. Cancer Res., 51, 4257–65.PubMedGoogle Scholar
  7. 7.
    Ioannides, C.G. and Whiteside, T.L. (1993) T cell recognition of human tumours: implications for molecular immunotherapy of cancer. Clin. Immunol Immunopathol, 66, 91–106.PubMedCrossRefGoogle Scholar
  8. 8.
    Jorgenson, J.L., Esser, U., St Groth, B.P. et al. (1992) Mapping T cell receptor-peptide contacts by various peptide immunization of single chain transgenics. Nature, 355,224–8.CrossRefGoogle Scholar
  9. 9.
    Jerome, K.R., Barnd, D.L., Bendt, K.M. et al. (1991) Cytotoxic T-lymphocytes derived from patients with breast adenocarcinoma recognize an epitope present on the protein core of a mucin molecule preferentially expressed by maUgnant cells.Cancer Res., 51, 2908–16.PubMedGoogle Scholar
  10. 10.
    Barnd, D.L., Lan, M.S., Metzgar, R.S. and Finn, O.J. (1989) Specific major histocompatibiUty complex-unrestricted recognition of tumourassociated mucins by human cytotoxic T cells. Proc. Natl Acad. Sci USA, 86, 7159–63.PubMedCrossRefGoogle Scholar
  11. 11.
    Zotter, S., Hageman, P.C., Lossnitzer, A. et al. (1988) Tissue and tumour distribution of human polymorphic epithelial mucin. Cancer Rev., 11–12, 55–101.Google Scholar
  12. 12.
    Gendler, S., Papadimitriou, J., Duhig, T. et al. (1988) A highly immunogenic region of a human polymorphic epithelial mucin expressed by carcinomas is made up of tandem repeats. J. Biol Chem., 263, 1282–3.Google Scholar
  13. 13.
    Papadimitriou, J.T. and Gendler, S. (1988) Molecular aspects of mucins. Cancer Rev., 11–12, 11–24.Google Scholar
  14. 14.
    Ioannides, C.G., Platsoucas, C.D., Kim, Y.P. et al. (1990) T cell functions in ovarian cancer patients treated with viral oncolysates: increased helper activity to immunoglobins production. Anticancer Res., 10, 645–54.PubMedGoogle Scholar
  15. 15.
    Jerome, K.R., Bu, D. and Finn, O. (1992) Expression of tumour associated epitopes on Epstein-Barr virus-immortalized B-cells and Burkitt’s lymphomas transfected with epithelial mucin complementary DNA. Cancer Res., 52, 5985–90.PubMedGoogle Scholar
  16. 16.
    Ioannides, C.G., Fisk, B., Tomasovic, B. et al. (1992) Induction of IL-2 receptor by TNF-α on cultured ovarian tumour associated lymphocytes. Cancer Immunol Immunother., 35, 83–91.PubMedCrossRefGoogle Scholar
  17. 17.
    Catipovic, B., Dal Porto, J., Mage, M. et al. (1992) Major histocompatibility complex conformational epitopes are peptide specific, J. Exp. Med., 176,1611–18.PubMedCrossRefGoogle Scholar
  18. 18.
    Parker, K.C., Bednarek, M.A., Hull, L.K. et al. (1992) Sequence motifs important for peptide binding to the human MHC class I molecule, HLA-A2, J.Immunol, 149, 2580–7.Google Scholar
  19. 19.
    Gammon, M.C., Bednarek, M.A., Biddison, W.E. et al. (1992) Endogenous loading of HLA- A2 molecules with an analog of the influenza virus matrix protein-derived peptide and its 26. inhibition by an exogenous peptide antagonist. J.mmunol, 148, 7–12.Google Scholar
  20. 20.
    Bluestone, J.A., Jameson, S., Miller, S. and Dick, R. (1992) Peptide induced conformational changes in class I heavy chains alter. major histocompatibility complex recognition. J. Exp. Med., 176, 1757–61.PubMedCrossRefGoogle Scholar
  21. 21.
    McMichael, A.J., Parham, P., Rust, N. and Brodsky P.M. (1980) A monoclonal antibody that recognizes an antigenic determinant shared by HLA-A2 and B-17. Hum. Immunol, 28. 1,121–31.CrossRefGoogle Scholar
  22. 22.
    Salter, R.D., Clayberger, C., Lomen, C.E. et al. (1987) In vitro mutagenesis at a single residue introduces B and T cell epitopes into a class I. HLA molecule. J. Exp. Med., 166, 283–8.PubMedCrossRefGoogle Scholar
  23. Layton, G.T., Devine, P.L., Warren, J.A. et al. (1990) Monoclonal antibodies reactive with the breast carcinoma-associated mucin coreprotein repeat sequence peptide also recognize the ovarian-associated sebaceous gland antigen. Tumour Biol, 11, 274–86.PubMedCrossRefGoogle Scholar
  24. 24.
    Ioannides, C.G., Itoh, K., Fox, P.E. et al. (1987) Identification of a second T cell antigen receptor in human and mouse by antipeptide gamma chain specific monoclonal antibody. Proc. Natl Acad. Sci USA, 84, 4244–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Matsushita, Y., Cleary, K.R., Ota, D.M. et al. (1990) Sialyl-dimeric Lewis-X antigen 33. expres- sed on mucin-like glycoproteins in colorectal cancer metastases. Lab. Invest., 63, 780–91.PubMedGoogle Scholar
  26. 26.
    Townsend, A.R.M., Rothbard, J., Gotch, P.M. et al. (1986) The epitopes of influenza nucleo- protein recognized by cytotoxic T-lympho- cytes can be defined with short peptides. Cell, 44,959–68.PubMedCrossRefGoogle Scholar
  27. 27.
    McGuckin, M.A., Wright, G. and Ward, B.G. (1990) Expression of a polymorphic epithelial mucin antigen defined by the monoclonal antibody BC2 in ovarian carcinoma. Use of the BC2 antibody for the detection of micrometastasis. Am. J. Pathol, 96,46–52.Google Scholar
  28. 28.
    Lie, R., Myers, N.B., Gorka, J. et al. (1990) Pepitide ligand-induced conformation and surface expression of the class I MHC molecule. Nature, 344,439–41.PubMedCrossRefGoogle Scholar
  29. 29.
    Guo, H.C., Jardetzky, T.S., Garrett, T.P.J, et al. (1992) Different length peptides bind to HLA- Aw68 similarly at their ends but bulge out in the middle. Nature, 360,364–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Palk, K., Rotzschke, O., Stevanovic, S. et al. (1991) Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature, 351, 290–6.CrossRefGoogle Scholar
  31. 31.
    Lloyd, K.O. (1992) Ovarian Cancer Mucins. Second International Workshop on Carcinoma-associated Mucins, Robinson College, Cambridge, August 2–6.Google Scholar
  32. 32.
    Pinn, O.J. (1992) Antigen-specific, MHC- unrestricted T cells. Biotherapy, 4,1239–49.Google Scholar
  33. 33.
    Henderson, R.A., Michel, H., Sakaguchi, K. et al. (1992) HLA-A2.1-associated peptides from a mutant cell line: a second pathway of antigen presentation. Science, 255,126Google Scholar

Copyright information

© Chapman & Hall 1995

Authors and Affiliations

  • C. G. Ioannides
  • B. Fisk
  • K. R. Jerome
  • B. Chesak
  • T. Irimura
  • J. T. Wharton
  • O. J. Finn

There are no affiliations available

Personalised recommendations