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Targeted Cellular Cytotoxicity

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Book cover Cytotoxic Cells: Recognition, Effector Function, Generation, and Methods

Abstract

Cell-mediated cytolysis occurs when a cytotoxic cell binds and delivers a “lethal hit” to a target cell. Several types of cells commonly found in blood are capable of performing cytolysis, including monocytes, neutrophils, eosinophils, natural killer (NK) cells, platelets, and T lymphocytes. The T-cell receptors (TCR) on T cells and the Fc γ receptors (Fc γ R) on myeloid cells, NK cells, and platelets are two well-characterized families of cell surface glycoproteins that are involved in binding target cells and triggering lysis.

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References

  • Andrew SM, Perez P, Nicholls PJ, George AJT, Huston JS, Oppermann H, Seal DM (1991): Production of single chain bispecific antibody by recombinant DNA technology. In: Bispecific Antibodies and Targeted Cellular Cytotoxicity, ’ Second International Conference, Seillac, France. October 9–13, 1990, Romet-Lemonne JL, Fanger MW, Segal DM, eds. Fondation Nationale de Transfusion Sanguine, Les Ulis, France. 197–199

    Google Scholar 

  • Bird RE, Hardman KD, Jacobson JW, Johnson S, Kaufman BM, Lee SM, Lee T, Pope SH, Riordan GS, Whitlow M (1988): Single-chain antigen-binding proteins. Science 242: 423–426

    Article  Google Scholar 

  • Brennan M, Davison PF, Paulus H (1985): Preparation of bispecific antibodies by chemical recombination of monoclonal immunoglobulin GI fragments. Science 229: 81–83

    Article  Google Scholar 

  • Brissinck J, Demanet C, Moser M, Leo L, Thielemans K (1991): Treatment of mice bearing BCL1 lymphoma with bispecific antibodies. J Immunol 147: 4019–4026

    Google Scholar 

  • Chaudhary VK, Queen C, Junghans RP, Waldmann TA, FitzGerald DJ, Pastan I (1989): A recombinant immunotoxin consisting of two antibody variable domains fused to pseudomonas exotoxin. Nature 339: 394–397

    Article  Google Scholar 

  • Clark MR, Waldmann H (1987): T-cell killing of target cells induced by hybrid antibodies: Comparison of two bispecific monoclonal antibodies. J Natl Cancer Inst 79: 1393–1401

    Google Scholar 

  • Clark M, Gilliland L, Waldmann H (1988): Hybrid antibodies for therapy. Prog Allergy 45: 31–49

    Google Scholar 

  • Corvalan JR, Smith W (1987): Construction and characterisation of a hybrid-hybrid monoclonal antibody recognising both carcinoembryonic antigen (CEA) and vinca alkaloids. Cancer Immunol Immunother 24: 127–132

    Google Scholar 

  • De Lau WBM, Heije K, Neefjes JJ, Oosterwegel M, Rozemuller E, Bast BJEG (1991): Absence of preferential homologous H/L chain association in hybrid hybridomas. J Immunol 146: 906–914

    Google Scholar 

  • De Lau WB, Van Loon AE, Heije K, Valerio D, Bast BJ (1989): Production of hybrid hybridomas based on HAT(s)-neomycin(r) double mutants. J Immunol Methods 117: 1–8

    Article  Google Scholar 

  • Demanet C, Brissinck J, Van Mechelen M, Leo O. Thiele-mans K (1991): Treatment of murine B cell lymphoma with bispecific monoclonal antibodies (anti—idiotype x anti-CD3). J Immunol 147: 1091–1097

    Google Scholar 

  • Erbe DV, Collins JE, Shen L, Graziano RF, Fanger MW (1990): The effect of cytokines on the expression and function of Fc receptors for IgG on human myeloid cells. Mol Immunol 27: 57–67

    Article  Google Scholar 

  • Ertl HC, Greene MI, Noseworthy JH, Fields BN, Nepom JT, Spriggs DR, Finberg RW (1982): Identification of idiotypic receptors on retrovirus-specific cytotoxic T cells. Proc Natl Acad Sci USA 79: 7479–7483

    Article  Google Scholar 

  • Fanger MW, Guyre PM (1991): Bispecific antibodies for targeted cellular cytotoxicity. Trends Biotechnol 9: 375–380

    Article  Google Scholar 

  • Fanger MW, Graziano RF, Shen L, Guyre PM (1989): Fc..R cytotoxicity exerted by mononuclear cells. Chem Immunol 47: 214–253

    Article  Google Scholar 

  • Garrido MA, Perez P, Titus JA, Valdayo MJ, Winkler DA, Barbieri SA, Wunderlich JR, Segal DM (1990a): Targeted cytotoxic cells in human peripheral blood lymphocytes. J Immunol 144: 2891–2898

    Google Scholar 

  • Garrido MA, Valdayo MJ, Winkler DF, Titus JA, Hecht TT, Perez P, Segal DM, Wunderlich JR (1990b): Targeting human T lymphocytes with bispecific antibodies to react against human ovarian carcinoma cells in nu/ nu mice. Cancer Res 50: 4227–4232

    Google Scholar 

  • Glennie MJ, McBride HM, Worth AT, Stevenson GT (1987): Preparation and performance of bispecific F(ab)’2 antibody containing thioether-linked Fab’.. fragments. J Immunol 139: 2367–2375

    Google Scholar 

  • Graziano RF, Fanger MW (1987a): Human monocyte-mediated cytotoxicity: The use of Ig-bearing hybridomas as target cells to detect trigger molecules on the monocyte cell surface. J Immunol 138: 945–950

    Google Scholar 

  • Graziano RF, Fanger MW (1987b): Fc_RI and Fc RII on monocytes and granulocytes are cytotoxic trigger molecules for tumor cells. J Immunol 139: 3536–3541

    Google Scholar 

  • Graziano RF, Looney RJ, Shen L, Fanger MW (1989): Fc..R-mediated killing by eosinophils. J Immunol 142: 230–235

    Google Scholar 

  • Henkart PA (1985): Mechanism of lymphocyte-mediated cytotoxicity. Annu Rev Immunol 3: 31–58

    Article  Google Scholar 

  • Henkart PA, Millard PJ, Reynolds CW, Henkart MP (1984): Cytolytic activity of purified cytoplasmic granules from cytotoxic rat large granular lymphocyte tumors. J Exp Med 160: 75–93

    Article  Google Scholar 

  • Huston JS, Levinson D, Mudgett-Hunter M, Tai MS, Novotny J, Margolies SN, Ridge RJ, Bruccoleri RE, Haber E, Crea R (1988): Protein engineering of antibody binding sites: Recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in Escherichia colie. Proc Natl Acad Sci USA 85: 5879–5883

    Article  Google Scholar 

  • Jung G, Muller-Eberhard HJ (1988): An in vitro model for tumor immunotherapy with antibody heteroconjugates. Immunol Today 9: 257–260

    Article  Google Scholar 

  • Jung G, Freimann U, Von Marschall Z, Reisfeld RA, Wilmanns W (1991): Target cell-induced T cell activation with bi-and trispecific antibody fragments. Eur J Immunol 21: 2431–2435

    Article  Google Scholar 

  • Jung G, Honsik CJ, Reisfeld RA, Muller-Eberhard HJ (1986): Activation of human peripheral blood mononuclear cells by anti-T3: Killing of tumor target cells coated with anti-target-anti-T3 conjugates. Proc Natl Acad Sci USA 83: 4479–4483

    Article  Google Scholar 

  • Jung G, Ledbetter JA, Muller-Eberhard HJ (1987): Induction of cytotoxicity in resting human T lymphocytes bound to tumor cells by antibody heterconjugates. Proc Natl Acad Sci USA 84: 4611–4615

    Article  Google Scholar 

  • Karawajew L, Micheel B, Behrsing O, Gaestel M (1987): Bispecific antibody-producing hybrid hybridomas selected by a fluorescence activated cell sorter. J Immunol Methods 96: 265–270

    Article  Google Scholar 

  • Karawajew L, Rudchenko S, Wlasik T, Trakht I, Rakitskaya V (1990): Flow sorting of hybrid hybridomas using the DNA stain Hoechst 33342. J Immunol Methods 129: 277–282

    Article  Google Scholar 

  • Karpovsky B, Titus JA, Stephany DA, Segal DM (1984): Production of target-specific effector cells using heterocross-linked aggregates containing anti-target cell and anti-Fe.. receptor antibodies. J Exp Med 160: 1686–1701

    Article  Google Scholar 

  • King TP, Li Y, Kochoumian L (1978): Preparation of protein conjugates via intermolecular disulfide bond formation. Biochemistry 17: 1499–1506

    Article  Google Scholar 

  • Koolwijk P, Rozemuller E, Stad RK, De Lau WB, Bast BJ (1988): Enrichment and selection of hybrid hybridomas by Percoll density gradiant centrifugation and fluorescent-activated cell sorting. Hybridoma 7: 217–225

    Article  Google Scholar 

  • Lancki DW, Ma DI, Havran WL, Fitch FW (1984): Cell surface structures involved in T cell receptor complex but involved in T cell activation. Immunol Rev 81: 65–94

    Article  Google Scholar 

  • Lanier LL, Yu G, Phillips Hi (1989): Co-association of CD3 zeta with a receptor (CD16) for IgG Fc on human natural killer cells. Nature 342: 803–805

    Article  Google Scholar 

  • Lanzavecchia A, Scheidegger D (1987): The use of hybrid hybridomas to target human cytotoxic T lymphocytes. Eur J Immunol 17: 105–111

    Article  Google Scholar 

  • Larrick JW, Wright SC (1990): Cytotoxic mechanism of tumor necrosis factor-alpha. FASEB J 4: 3215–3223

    Google Scholar 

  • Leeuwenberg JTM, Spits H, Tax WJM, Capel PJA (1985): Induction of nonspecific cytotoxicity by monoclonal anti-T3 antibodies. J Immunol 134: 3770–3775

    Google Scholar 

  • Leo O, Foo M, Segal DM, Shevach E, Bluestone JA (1987): Activation of murine T lymphocytes with monoclonal antibodies: Detection on Lyt2+ cells of an antigen not associated with the T cell activation. J Immunol 139: 1214–1222

    Google Scholar 

  • Liu MA, Kranz DM, Kurnick JT, Boyle LA, Levy R, Eisen HN (1985): Heteroantibody duplexes target cells for lysis by cytotoxic T lymphocytes. Proc Natl Acad Sci USA 82: 8648–8652

    Article  Google Scholar 

  • Lovchik JC, Hong R (1977): Antibody-dependent cell-mediated cytolysis (ADCC): analyses and projections. Prog Allergy 22: 1–44

    Google Scholar 

  • Mezzanzanica D, Garrido MA, Noblock DS, Daddona PE, Andrew SM, Zurawski VR, Segal DM, Wunderlich JR (1991): Human T-lymphocytes targeted against an established ovarian carcinoma with bispecific F(ab’), antibody prolong host survival in a murine xenograft model. Cancer Res 51: 5716–5721

    Google Scholar 

  • Milstein C, Cuello AC (1983): Hybrid hybridomas and their use in immunohistochemistry. Nature 305: 537–540

    Article  Google Scholar 

  • Milstein C, Cuello AC (1984): Hybrid hybridomas and production of bispecific monoclonal antibodies. Immunol Today 5: 299–304

    Article  Google Scholar 

  • Miotti S, Canevari S, Menard S, Mezzanzanica D, Porro G, Pupa SM, Regazzoni M, Tagliabue E, Colnaghi MI (1987): Characterization of human ovarian carcinoma-associated antigens defined by novel monoclonal antibodies with tumor-restricted specificity. Int Cancer 39: 297–303

    Article  Google Scholar 

  • Moran TM, Usuba O, Kuzu Y, Schulman J, Bona CA (1991): Inhibition of multicycle influenza virus replication by hybrid antibody-directed cytotoxic T lymphocyte lysis. J Immunol 146: 321–326

    Google Scholar 

  • Moretta A, Poggi A, Pende D, Tripodi G, Orengo AM, Pella N, Augugliaro R, Bottino C, Ciccone E, Moretta L (1991): CD69-mediated pathway of lymphocyte activation: Anti-CD69 monoclonal antibodies trigger the cytolytic activity of different lymphoid effector cells with the exception of cytolytic T lymphocytes expressing T cell receptor a/ß. J Exp Med 174: 1393–1398

    Article  Google Scholar 

  • Nisonoff A, Mandy WJ (1962): Quantitative estimation of the hybridization of rabbit antibodies. Nature 194: 355–359

    Article  Google Scholar 

  • Nitta T, Ikeda M, Azuma A, Yagita H, Sato K, Okumura K, Steinman L (1991): Clinical results of specific targeting therapy against human malignant glioma and prospects for future reagents based on the restricted T cell receptor repertoire in tumor infiltrating lymphocytes. In: Bispecific Antibodies and Targeted Cellular Cytoxicity. Second International Conference, Seillac, France October 9–13, 1990, Romet-Lemonne JL, Fanger MW, Segal DM, eds. Les Ulis, France: Foundation Nationale de Transfusion Sanguine 233–235

    Google Scholar 

  • Nitta T, Sato K, Yagita H, Okumura K, Ishii S (1990): Preliminary trial of specific targeting therapy against malignant glioma. Lancet 335: 368–371

    Article  Google Scholar 

  • Old H (1985): Tumor necrosis factor (TNF). Science 230: 630–632

    Article  Google Scholar 

  • Ortho Multicenter Transplant Study Group (1985): A randomized clinical trial of OKT3 monoclonal antibody for acute rejection of cadaveric renal transplants. N Engl J Med 313: 337–342

    Article  Google Scholar 

  • Paya CV, McKean DJ, Segal DM, Schoon RA, Schowalter SD, Leibson PJ (1989): Heteroconjugate antibodies enhance cell-mediated anti-herpes simplex virus immunity. J Immunol 142: 666–671

    Google Scholar 

  • Perez P, Hoffman RW, Shaw S, Bluestone JA, Segal DM (1985): Specific targeting of cytotoxic T cells by anti-T3 linked to anti-target cell antibody. Nature 316: 354–356

    Article  Google Scholar 

  • Perez P, Hoffman RW, Titus JA, Segal DM (1986a): Specific targeting of human peripheral blood T cells by heteroaggregates containing anti-T3 crosslinked to anti-target cell antibodies. J Exp Med 163: 166–178

    Article  Google Scholar 

  • Perez P, Titus JA, Lotze MT, Cuttitta F, Longo DL, Groves ES, Rabin H, Durda PJ, Segal DM (1986b): Specific lysis of human tumor cells by T cells coated with anti-T3 crosslinked to anti-tumor antibody. J Immunol 137: 2069–2072

    Google Scholar 

  • Podack ER, Kupfer A (1991): T-cell effector functions: Mechanisms for delivery of cytotoxicity and help. Annu Rev Cell Biol 7: 479–504

    Article  Google Scholar 

  • Qian JH, Titus JA, Andrew SM, Mezzanzanica D, Garrido MA, Wunderlich JR, Segal DM (1991): Human PBL targeted with bispecific antibodies release cytokines that are essential for inhibiting tumor growth. J Immunol 146: 3250–3256

    Google Scholar 

  • Huston JS, Levinson D, Mudgett-Hunter M, Tai MS, Novotny J, Margolies SN, Ridge RJ, Bruccoleri RE, Haber E, Crea R (1988): Protein engineering of antibody binding sites: Recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in Escherichia colie. Proc Natl Acad Sci USA 85: 5879–5883

    Article  Google Scholar 

  • Segal DM, Snider DP (1989): Targeting and activation of cytotoxic lymphocytes. Chem Immunol 47: 179–213

    Article  Google Scholar 

  • Segal DM, Wunderlich JR (1988): Targeting of cytotoxic cells with heterocrosslinked antibodies. Cancer Invest 6: 83–92

    Article  Google Scholar 

  • Segal DM, Dower SK, Titus JA (1983): The role of non-immune IgG in controlling IgG-mediated effector functions. Mol Immunol 20: 1177–1189

    Article  Google Scholar 

  • Seth A, Gote L, Nagarkatti M, Nagarkatti PS (1991): T-cell-receptor-independent activation of cytolytic activity of cytotoxic T lymphocytes mediated through CD44 and gp90MEL-I4 Proc nat Acad Sci USA 88: 7877–7881

    Article  Google Scholar 

  • Shalaby MR, Shepard HM, Presta L, Rodrigues ML, Beverley PCL, Feldmann M, Carter P (1992): Development of humanized bispecific antibodies reactive with cytotoxic lymphocytes and tumor cells over-expressing the HER2 protooncogene. J Exp Med 175: 217–225

    Article  Google Scholar 

  • Shen LR, Graziano RF, Fanger MW (1989): The functional properties of Fc gamma RI, II and III on myeloid cells: A comparative study of killing of erythrocytes and tumor cells mediated through the different Fc receptors. Mol Immunol 26: 959–969

    Article  Google Scholar 

  • Shen L, Guyre PM, Anderson CL, Fanger MW (1986): Heteroantibody-mediated cytotoxicity: Antibody to the high affinity Fc receptor for IgG mediates cytotoxicity by human monocytes that is enhanced by interferon-y and is not blocked by human IgG. J Immunol 137: 3378–3382

    Google Scholar 

  • Shi T, Eaton AM, Ring DB (1991): Selection of hybrid hybridomas by flowing cytometry using a new combination of fluorescent vital stains. J Immunol Methods 141: 165–175

    Article  Google Scholar 

  • Siliciano RF, Pratt JC, Schmidt RE, Ritz J, Reinherz EL (1985): Activation of cytotoxic T lymphocyte and natural killer cell function through the TI sheep erthrocyte binding protein. Nature 317: 428–429

    Article  Google Scholar 

  • Songsivilai S, Lachmann PJ (1990): Bispecific antibody: A tool for diagnosis and treatment of disease. Clin Exp Immunol 79: 315–321

    Article  Google Scholar 

  • Songsivilai S, Clissold PM, Lachmann PJ (1989): A novel strategy for producing chimeric bispecific antibodies by gene transfection. Biochem Biophys Res Commun 164: 271–276

    Article  Google Scholar 

  • Springer TA (1990): Adhesion receptors of the immune system. Nature 346: 425–434

    Article  Google Scholar 

  • Staerz UD, Bevan MJ (1986a): Hybrid hybridoma producing a bispecific monoclonal antibody that can focus effector T-cell activity. Proc Natl Acad Sci USA 83: 1453–1457

    Article  Google Scholar 

  • Bird RE, Hardman KD, Jacobson JW, Johnson S, Kaufman BM, Lee SM, Lee T, Pope SH, Riordan GS, Whitlow M (1988): Single-chain antigen-binding proteins. Science 242: 423–426

    Article  Google Scholar 

  • Staerz UD, Kanagawa O, Bevan MJ (1985): Hybrid antibodies can target sites for attack by T cells. Nature 314: 628–631

    Article  Google Scholar 

  • Suresh MR, Cuello AC, Milstein C (1986): Advantages of bispecific hybridomas in one-step immunocytochemistry and immunoassays. Proc Natl Acad Sci USA 83: 7989–7993

    Article  Google Scholar 

  • Tai MS, Mudgett-Hunter M, Levinson D, Wu GM, Haber E, Oppermann H, Huston JS (1990): A bifunctional fusion protein containing Fe-binding fragment B of staphylococcal protein A amino terminal to antidigoxin single-chain Fv. Biochemistry 29: 8024–8030

    Article  Google Scholar 

  • Titus JA, Garrido MA, Hecht TT, Winkler DF, Wunderlich JR, Segal DM (1987a): Human T cells targeted with anti-T3 crosslinked to anti-tumor antibody prevent tumor growth in nude mice. J Immunol 138: 4018–4022

    Google Scholar 

  • Titus JA, Perez P, Kaubisch A, Garrido MA, Segal DM (1987b): Human K/NK cells targeted with heterocrosslinked antibodies specifically lyse tumor cells in vitro and prevent tumor growth in vivo. J Immunol 139: 3153–3158

    Google Scholar 

  • Traunecker A, Lanzavecchia A, Karjalainen K (1991): Bispecific single chain molecules (Janusins) target cytotoxic lymphocytes on HIV infected cells. EMBO J 10: 3655–3659

    Google Scholar 

  • Tschopp J, Nabholz M (1990): Perforin-mediated target cell lysis by cytolytic T lymphocytes. Annu Rev Immunol 8: 279–302

    Article  Google Scholar 

  • Glennie MJ, McBride HM, Worth AT, Stevenson GT (1987): Preparation and performance of bispecific F(ab)’2 antibody containing thioether-linked Fab’.. fragments. J Immunol 139: 2367–2375

    Google Scholar 

  • Tutt A, Stevenson GT, Glennie MJ (1991b): Trispecific F(ab’)3 derivatives that use cooperative signaling via the TCR/CD3 complex and CD2 to activate and redirect resting cytotoxic T cells. J Immunol 147: 60–69

    Google Scholar 

  • Urnovitz HB, Chang Y, Scott M, Fleischmann J, Lynch RG (1988): IgA:IgM and IgA:IgA hybrid hybridomas secrete heteropolymeric immunoglobulins that are polyvalent and bispecific. J Immunol 140: 558–563

    Google Scholar 

  • Wegener A-MK, Letourneur F, Hoeveler A, Brocker T, Luton F, Malissen B (1992): The T cell receptor/CD3 complex is composed of at least two autonomous transduction molecules. Cell 68: 83–95

    Article  Google Scholar 

  • Weiner GJ, Hillstrom JR (1991): Bispecific anti-idiotype/ anti-CD3 antibody therapy of murine B cell lymphoma. J Immunol 147: 4035–4044

    Google Scholar 

  • Winter G, Milstein C (1991): Man-made antibodies. Nature 349: 293–299

    Article  Google Scholar 

  • Wong JT, Colvin RB (1987): Bispecific monoclonal antibodies: Selective binding and complement fixation to cells that express two different surface antigens. J Immunol 139: 1369–1374

    Google Scholar 

  • Zarling JM, Moran PA, Grosmarie LS, McClure J, Shriver K, Ledbetter JA (1988): Lysis of cells infected with HIV-1 by human lymphocytes targeted with monoclonal antibody heteroconjugates. J Immunol 140: 2609–2613

    Google Scholar 

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Authors
  1. David M. Segal
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  2. Carolina R. Jost
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  3. Andrew J. T. George
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Editor information

Editors and Affiliations

  1. Laboratory of Immunology, Biochemistry and Immunopharmacology Unit, NIH-NIAID, 20892, Bethesda, Maryland, USA

    Michail V. Sitkovsky

  2. Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, 20892, Bethesda, Maryland, USA

    Pierre A. Henkart

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© 1993 Birkhäuser Boston

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Segal, D.M., Jost, C.R., George, A.J.T. (1993). Targeted Cellular Cytotoxicity. In: Sitkovsky, M.V., Henkart, P.A. (eds) Cytotoxic Cells: Recognition, Effector Function, Generation, and Methods. Birkhäuser Boston. https://doi.org/10.1007/978-1-4684-6814-4_9

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  • DOI: https://doi.org/10.1007/978-1-4684-6814-4_9

  • Publisher Name: Birkhäuser Boston

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