Abstract
Cytotoxic T lymphocytes (CTLs) recognize peptide antigens associated with cell surface major histocompatibility complex (MHC) molecules. The identification of tumor cell-derived peptides capable of eliciting anti-tumor CTL responses would enable the design of antigen-specific immunotherapies. Our strategy to identify such potentially therapeutic peptides relies on selecting high-affinity MHC binders from known tumor-associated antigens. These peptides are subsequently tested for their ability to induce CTLs capable of killing tumor cells. With this strategy, we have identified a nine-residue epitope, derived from the product of the tumor-associated gene MAGE-3, which has the capacity to induce in vitro CTLs that kill melanoma and other tumor cell lines. These results show the primary in vitro induction of tumor-specific human CTLs and illustrate the feasibility of ex vivo antigen-specific approaches to the immunological therapy of cancer.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barnstable C. J., Bodmer W. F., Brown G., Galfre G., Milstein C., Williams A. F., Ziegler A. Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell. 1978 May;14(1):9–20. doi: 10.1016/0092-8674(78)90296-9. [DOI] [PubMed] [Google Scholar]
- Bjorkman P. J., Parham P. Structure, function, and diversity of class I major histocompatibility complex molecules. Annu Rev Biochem. 1990;59:253–288. doi: 10.1146/annurev.bi.59.070190.001345. [DOI] [PubMed] [Google Scholar]
- Carbone F. R., Bevan M. J. Induction of ovalbumin-specific cytotoxic T cells by in vivo peptide immunization. J Exp Med. 1989 Mar 1;169(3):603–612. doi: 10.1084/jem.169.3.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carbone F. R., Moore M. W., Sheil J. M., Bevan M. J. Induction of cytotoxic T lymphocytes by primary in vitro stimulation with peptides. J Exp Med. 1988 Jun 1;167(6):1767–1779. doi: 10.1084/jem.167.6.1767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeMars R., Spies T. New genes in the MHC that encode proteins for antigen processing. Trends Cell Biol. 1992 Mar;2(3):81–86. doi: 10.1016/0962-8924(92)90077-z. [DOI] [PubMed] [Google Scholar]
- Deres K., Schild H., Wiesmüller K. H., Jung G., Rammensee H. G. In vivo priming of virus-specific cytotoxic T lymphocytes with synthetic lipopeptide vaccine. Nature. 1989 Nov 30;342(6249):561–564. doi: 10.1038/342561a0. [DOI] [PubMed] [Google Scholar]
- Falk K., Rötzschke O., Stevanović S., Jung G., Rammensee H. G. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature. 1991 May 23;351(6324):290–296. doi: 10.1038/351290a0. [DOI] [PubMed] [Google Scholar]
- Feltkamp M. C., Smits H. L., Vierboom M. P., Minnaar R. P., de Jongh B. M., Drijfhout J. W., ter Schegget J., Melief C. J., Kast W. M. Vaccination with cytotoxic T lymphocyte epitope-containing peptide protects against a tumor induced by human papillomavirus type 16-transformed cells. Eur J Immunol. 1993 Sep;23(9):2242–2249. doi: 10.1002/eji.1830230929. [DOI] [PubMed] [Google Scholar]
- Germain R. N., Margulies D. H. The biochemistry and cell biology of antigen processing and presentation. Annu Rev Immunol. 1993;11:403–450. doi: 10.1146/annurev.iy.11.040193.002155. [DOI] [PubMed] [Google Scholar]
- Greenberg P. D. Adoptive T cell therapy of tumors: mechanisms operative in the recognition and elimination of tumor cells. Adv Immunol. 1991;49:281–355. doi: 10.1016/s0065-2776(08)60778-6. [DOI] [PubMed] [Google Scholar]
- Houbiers J. G., Nijman H. W., van der Burg S. H., Drijfhout J. W., Kenemans P., van de Velde C. J., Brand A., Momburg F., Kast W. M., Melief C. J. In vitro induction of human cytotoxic T lymphocyte responses against peptides of mutant and wild-type p53. Eur J Immunol. 1993 Sep;23(9):2072–2077. doi: 10.1002/eji.1830230905. [DOI] [PubMed] [Google Scholar]
- Hunt D. F., Henderson R. A., Shabanowitz J., Sakaguchi K., Michel H., Sevilir N., Cox A. L., Appella E., Engelhard V. H. Characterization of peptides bound to the class I MHC molecule HLA-A2.1 by mass spectrometry. Science. 1992 Mar 6;255(5049):1261–1263. doi: 10.1126/science.1546328. [DOI] [PubMed] [Google Scholar]
- Jardetzky T. S., Lane W. S., Robinson R. A., Madden D. R., Wiley D. C. Identification of self peptides bound to purified HLA-B27. Nature. 1991 Sep 26;353(6342):326–329. doi: 10.1038/353326a0. [DOI] [PubMed] [Google Scholar]
- Kast W. M., Roux L., Curren J., Blom H. J., Voordouw A. C., Meloen R. H., Kolakofsky D., Melief C. J. Protection against lethal Sendai virus infection by in vivo priming of virus-specific cytotoxic T lymphocytes with a free synthetic peptide. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2283–2287. doi: 10.1073/pnas.88.6.2283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lanzavecchia A. Identifying strategies for immune intervention. Science. 1993 May 14;260(5110):937–944. doi: 10.1126/science.8493532. [DOI] [PubMed] [Google Scholar]
- Long E. O., Rosen-Bronson S., Karp D. R., Malnati M., Sekaly R. P., Jaraquemada D. Efficient cDNA expression vectors for stable and transient expression of HLA-DR in transfected fibroblast and lymphoid cells. Hum Immunol. 1991 Aug;31(4):229–235. doi: 10.1016/0198-8859(91)90092-n. [DOI] [PubMed] [Google Scholar]
- Macatonia S. E., Taylor P. M., Knight S. C., Askonas B. A. Primary stimulation by dendritic cells induces antiviral proliferative and cytotoxic T cell responses in vitro. J Exp Med. 1989 Apr 1;169(4):1255–1264. doi: 10.1084/jem.169.4.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Melief C. J. Tumor eradication by adoptive transfer of cytotoxic T lymphocytes. Adv Cancer Res. 1992;58:143–175. doi: 10.1016/s0065-230x(08)60294-8. [DOI] [PubMed] [Google Scholar]
- Neefjes J. J., Momburg F. Cell biology of antigen presentation. Curr Opin Immunol. 1993 Feb;5(1):27–34. doi: 10.1016/0952-7915(93)90077-6. [DOI] [PubMed] [Google Scholar]
- Rammensee H. G., Falk K., Rötzschke O. Peptides naturally presented by MHC class I molecules. Annu Rev Immunol. 1993;11:213–244. doi: 10.1146/annurev.iy.11.040193.001241. [DOI] [PubMed] [Google Scholar]
- Rebaï N., Malissen B. Structural and genetic analyses of HLA class I molecules using monoclonal xenoantibodies. Tissue Antigens. 1983 Aug;22(2):107–117. doi: 10.1111/j.1399-0039.1983.tb01176.x. [DOI] [PubMed] [Google Scholar]
- Rosenberg S. A., Spiess P., Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science. 1986 Sep 19;233(4770):1318–1321. doi: 10.1126/science.3489291. [DOI] [PubMed] [Google Scholar]
- Ruppert J., Sidney J., Celis E., Kubo R. T., Grey H. M., Sette A. Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. Cell. 1993 Sep 10;74(5):929–937. doi: 10.1016/0092-8674(93)90472-3. [DOI] [PubMed] [Google Scholar]
- Shimizu Y., DeMars R. Production of human cells expressing individual transferred HLA-A,-B,-C genes using an HLA-A,-B,-C null human cell line. J Immunol. 1989 May 1;142(9):3320–3328. [PubMed] [Google Scholar]
- Townsend A., Bodmer H. Antigen recognition by class I-restricted T lymphocytes. Annu Rev Immunol. 1989;7:601–624. doi: 10.1146/annurev.iy.07.040189.003125. [DOI] [PubMed] [Google Scholar]
- Traversari C., van der Bruggen P., Luescher I. F., Lurquin C., Chomez P., Van Pel A., De Plaen E., Amar-Costesec A., Boon T. A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-A1 by cytolytic T lymphocytes directed against tumor antigen MZ2-E. J Exp Med. 1992 Nov 1;176(5):1453–1457. doi: 10.1084/jem.176.5.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yewdell J. W., Bennink J. R. Cell biology of antigen processing and presentation to major histocompatibility complex class I molecule-restricted T lymphocytes. Adv Immunol. 1992;52:1–123. doi: 10.1016/s0065-2776(08)60875-5. [DOI] [PubMed] [Google Scholar]
- Zakut R., Topalian S. L., Kawakami Y., Mancini M., Eliyahu S., Rosenberg S. A. Differential expression of MAGE-1, -2, and -3 messenger RNA in transformed and normal human cell lines. Cancer Res. 1993 Jan 1;53(1):5–8. [PubMed] [Google Scholar]
- van der Bruggen P., Traversari C., Chomez P., Lurquin C., De Plaen E., Van den Eynde B., Knuth A., Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991 Dec 13;254(5038):1643–1647. doi: 10.1126/science.1840703. [DOI] [PubMed] [Google Scholar]