Abstract
A number of cell surface molecules with specificity to tumour cells have been identified and monoclonal antibodies (mAb) to some of these antigens have been used for targeting tumour cells in vivo. We have sought to link the powerful effector mechanisms of cytotoxic T-cells with the specificity of mAb, by targeting recombinant HLA class I molecules to tumour cells using an antibody delivery system. Soluble recombinant MHC class I/peptide complexes including HLA-A2.1 refolded around an immunodominant peptide from the HIV gag protein (HLA-A2/gag) were synthesized, and the stability of these complexes at 37°C was confirmed by enzyme-linked immunosorbent assay using a conformation-specific antibody. MHC class I-negative lymphoma cells (Daudi) were labelled with a biotinylated mAb specific for a cell surface protein (anti-CD20) then linked to soluble biotinylated HLA-A2/gag complexes using an avidin bridge. Flow cytometry revealed strong labelling of lymphoma cells with HLA-A2/gag complexes (80-fold increase in mean channel fluorescence). CTL specific for HLA-A2/gag efficiently lysed complex-targeted cells, while control CTL (specific for an HLA-A2.1-restricted epitope of melan-A) did not. Similarly, SK-mel-29 melanoma cells were also efficiently lysed by HLA-A2/gag-specific CTL when HLA-A2/gag complexes were linked to their surface via the HMW-MAA specific anti-melanoma antibody 225.28s. With further consideration to the in vivo stability of the MHC class I/peptide complexes, this system could prove a new strategy for the immunological therapy of cancer. © 2000 Cancer Research Campaign
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Altman JD, Moss PAH, Goulder PJR, Barouch DH, McHeyzer-Williams MG, Bell JL, McMichael AJ and Davis MM (1996) Phenotypic analysis of antigen-specific T lymphocytes. Science 274: 94–96
Berenson RJ, Bensinger WI, Kalamasz D and Martin P (1986) Elimination of Daudi lymphoblasts from human bone marrow using avidin–biotin immunoadsorption. Blood 67: 509–515
Bodmer WF, Browning MJ, Krausa P, Rowan A, Bicknell DC and Bodmer JG (1993) Tumour escape from immune response by variation in HLA expression and other mechanisms. Ann NY Acad Sci 690: 42–49
Buraggi GL, Callegaro L, Mariani G, Turrin A, Cascinelli N, Attili A, Bombardieri E, Terno G, Plassio G, Dovis M, Mazzuca N, Natali PG, Scassellati GA, Rosa U and Ferrone S (1985) Imaging with131I-labeled monoclonal antibodies to a high molecular weight melanoma-associated antigen in patients with melanoma: efficacy of whole immunoglobulin and its F(ab′)2fragments. Cancer Res 45: 3378–3387
Callan MFC, Tan L, Annels N, Ogg GS, Wilson JDK, O'Callaghan CA, Steven N, McMichael AJ and Rickinson AB (1998) Direct visualisation of antigen-specific CD8+ T cells during the primary immune response to Epstein–Barr virus in vivo. J Exp Med 187: 1395–1402
Davies HS, Pollard SG and Calne RY (1989) Soluble HLA antigens in the circulation of liver graft recipients. Transplantation 47: 524–527
Dohlsten M, Hedlund G, Akerblom E, Lando PA and Kalland T (1991) Monoclonal antibody-targeted superantigens: a different class of anti-tumour agents. Proc Natl Acad Sci USA 88: 9287–9291
Dohlsten M, Sundstedt A, Bjorkland M, Hedlund G and Kalland T (1993) Superantigen-induced cytokines suppress growth of human colon-carcinoma cells. Int J Cancer 54: 482–488
Dohlsten M, Lando PA, Bjork P, Abrahmsen L, Ohlsson L, Lind P and Kalland T (1995) Immunotherapy of human colon cancer by antibody-targeted superantigens. Cancer Immunol Immunother 41: 162–168
Eisenbarth GS, Haynes BF, Schroer JA and Fauci AS (1980) Production of monoclonal antibodies reacting with peripheral blood mononuclear cell surface differentiation antigens. J Immunol 124: 1237–1244
Elliot TJ and Eisen HN (1988) Allorecognition of purified major histocompatability complex glyco proteins by cytotoxic T lymphocytes. Proc Natl Acad Sci USA 85: 2728–2732
Garboczi DN, Hung DT and Wiley DC (1992) HLA-A2–peptide complexes: refolding and crystallization of molecules expressed in Escherichia coli and complexed with single antigenic peptides. Proc Natl Acad Sci USA 89: 3429–3433
Hird V, Maraveyas A, Snook D, Dhokia B, Soutter WP, Meares C, Stewart JS, Mason P, Lambert HE and Epenetos AA (1993) Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody. Br J Cancer 68: 403–406
Kane KP, Sherman LA and Mescher MF (1989) Molecular interactions required for triggering alloantigen-specific cytolytic T lymphocytes. J Immunol 142: 4153–4160
Klein E, Klein G, Nadkarni JS, Nadkarni JJ, Wigzell H and Clifford P (1968) Surface IgM-kappa specificty on a Burkitt lymphoma cell in vivo and in derived cell culture lines. Cancer Res 28: 1300–1310
Knuth A, Wolfel T, Klehmann E, Boon T and Meyer zum Buschenfelde KH (1989) Cytolytic T-cell clones against an autologous human melanoma: specificty study and definition of three antigens by immunoselection. Proc Natl Acad Sci USA 86: 2804–2808
Ledermann JA, Begent RH, Massof C, Kelly AM, Adam T and Bagshawe K (1991) A phase-1 study of repeated therapy with radiolabelled antibody to carcinoembryonic antigen using intermittent or continuous administration of cyclosporin A to suppress the immune response. Int J Cancer 47: 659–664
Lone YC, Motta I, Mottez E, Guilloux Y, Lim A, Demay F, Levraud JP, Kourilsky P and Abastado JP (1998) In vitro induction of specific cytotoxic T lymphocytes using recombinant single-chain MHC class I/peptide complexes. J Immunother 21: 293–294
Magnani P, Paganelli G, Modorati G, Zito F, Songini C, Sudati F, Koch P, Maecke HR, Brancato R, Siccardi AG and Fazio F (1995) Quantitative comparison of direct antibody labeling and tumor pre-targeting in uveal melanoma. J Nucl Med 37: 967–971
Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A and Levy R (1994) Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood 84: 2457–2466
Moro M, Pelagi M, Fulci G, Paganelli G, Dellabona P, Casorati G, Siccardi AG and Corti A (1997) Tumor cell targeting with antibody–avidin complexes and biotinylated tumor necrosis factor alpha. Cancer Res 57: 1922–1928
Neri D, Natali PG, Petrul H, Soldani P, Nicotra MR, Vola R, Rivella A, Creighton AM, Neri P and Mariani M (1996) Recombinant anti-human melanoma antibodies are versatile molecules. J Invest Dermatol 107: 164–170
Ogg GS,X, Jin S, Bonhoeffer PR, Dunbar MA, Nowak S, Monard JP, Segal Y, Cao SL, Rowland-Jones V, Cerundolo A, Hurley M, Markowitz DD, Ho DF, Nixon and McMichael AJ (1998) Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 279: 2103
Paganelli G, Magnani P, Zito F, Villa E, Sudati F, Lopalco L, Rosetti C et al; (1991) Three-step monoclonal antibody tumor targeting in carcinoembryonic antigen-positive patients. Cancer Res 51: 5960–5966
Parham P, Barnstable C and Bodmer W (1979) Use of a monoclonal antibody (W6/32) in structural studies of HLA-A,B,C antigens. J Immunol 123: 342–349
Parker KC, Bednarek MA, Hull LK, Utz U, Cunningham B, Zweerik HJ, Biddison WE and Coligan JE (1992) Sequence motifs important for peptide binding to the human MHC class I molecule HLA-A2. J Immunol 149: 3580–3587
Perez P, Hoffman RW, Shaw S, Bluestone JA and Segal DM (1985) Specific targeting of cytotoxic T cells by anti-T3 linked to an anti-target cell antibody. Nature 316: 354–356
Riethmuller G and Johnson JP (1992) Monoclonal antibodies in the detection and therapy of micrometastatic epithelial cancers. Curr Opin Immunol 4: 647–655
Riethmuller G, Holz E, Schlimok G, Schmiegel W, Raab R, Hoffken K, Gruber R, Funke I, Pichlmaier H, Hirche H, Buggisch P, Witte J and Pichlmayr R (1998) Monoclonal antibody therapy for resected Dukes' C colorectal cancer: seven-year outcome of a multicenter randomized trial. J Clin Oncol 16: 1788–1794
Romero P, Gervois N, Schneider J, Escobar P Valmori D, Pannetier C, Steinle A, Wolfel T, Lienard D, Brichard V, van Pel A, Jotereau F and Cerottini JC (1997) Cytolytic T lymphocyte recognition of the immunodominant HLA-A*0201-restricted Melan-A/MART-1 antigenic peptide in melanoma. J Immunol 159: 2366
Schneck J, Lee Maloy W, Coligan JE and Margulies DH (1989) Inhibition of an allospecific T cell hybridoma by soluble class I proteins and peptides: estimation of the affinity of a T cell receptor for MHC. Cell 56: 47–55
Terness P, Dufter C, Otto G and Opelz G (1996) Allograft survival following immunization with membrane-bound or soluble peptide MHC class I donor antigens: factors relevant for the induction of rejection by indirect recognition. Transplant Int 9: 2–8
Toshitani K, Braud V, Browning MJ, Murray N, McMichael AJ and Bodmer WF (1996) Expression of a single chain HLA class I molecule in a human cell line: presentation of exogenous peptide and processed antigen to cytotoxic T lymphocytes. Proc Natl Acad Sci USA 93: 236–240
Townsend A and Bodmer H (1989) Antigen recognition by class I restricted T lymphocytes. Annu Rev Immunol 7: 601–624
Valone FH, Kaufman PA, Guyre PM, Lewis LD, Memoli V, Deo Y, Graziano R, Fisher JL, Meyer L, Mrozek-Orlowski M, Wardwell K, Guyre V, Morley TL, Arvizu C and Fanger MW (1995) Phase Ia/Ib trial of bispecific antibody MDX-210 in patients with advanced breast or ovarian cancer that overexpresses the proto-oncogene HER-2/neu. J Clin Oncol 13: 2281–2292
Weiner LM, Alpaugh RK, Amoroso AR, Adams GP, Ring DB and Barth MW (1996) Human neutrophil interactions of a bispecific monoclonal antibody targeting tumor and human Fc gamma RIII. Cancer Immunol Immunother 42: 141–150
Wilson JL, Cunningham AC and Kirby JA (1995) Alloantigen presentation by B cells: analysis of the requirement for B cell activation. Immunology 86: 325–333
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Ogg, G., Dunbar, P., Cerundolo, V. et al. Sensitization of tumour cells to lysis by virus-specific CTL using antibody-targeted MHC class I/peptide complexes. Br J Cancer 82, 1058–1062 (2000). https://doi.org/10.1054/bjoc.1999.1042
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1054/bjoc.1999.1042
Keywords
This article is cited by
-
Antibody–peptide–MHC fusion conjugates target non-cognate T cells to kill tumour cells
Cancer Immunology, Immunotherapy (2013)
-
Novel antibodies as anticancer agents
Oncogene (2007)
-
Malignant melanoma and bone resorption
British Journal of Cancer (2006)
-
Antibody-mediated targeting of human single-chain class I MHC with covalently linked peptides induces efficient killing of tumor cells by tumor or viral-specific cytotoxic T lymphocytes
Cancer Immunology, Immunotherapy (2005)
-
Induction of viral and tumour specific CTL responses using antibody targeted HLA class I peptide complexes
British Journal of Cancer (2002)