Specific targeting of cytotoxic T cells by anti-T3 linked to anti-target cell antibody

Perez, Pilar; Hoffman, Robert W.; Shaw, Stephen; Bluestone, Jeffrey A.; Segal, David M.

doi:10.1038/316354a0

Cited by 337Monoclonal and Polyclonal Antibodies ResearchT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

Specific targeting of cytotoxic T cells by anti-T3 linked to anti-target cell antibody

Perez, Pilar, Hoffman, Robert W., Shaw, Stephen, Bluestone, Jeffrey A., Segal, David M.·1985·Nature

DOI 10.1038/316354a0

Open this paper in CoChat — free account

Abstract

The specificity of cytotoxic T lymphocytes (Tc) cells is conferred by an antigen-specific receptor, Ti, which in humans is physically associated with an invariant cell-surface glycoprotein, T3. Monoclonal antibodies specific for either T3 and Ti are able to elicit a variety of T-cell responses such as lymphokine production, mitogenesis and cytotoxicity. For example, human Tc cells lyse anti-T3-expressing hybridoma cells, but not cells of other specificity, presumably because anti-T3 on the hybridoma cells binds to T3 on the Tc cells and triggers lysis. Here, we have adapted approaches used in a different cytotoxic effector system, antibody-dependent cellular cytotoxicity (ADCC), to alter the specificity of Tc cell. Studies of ADCC showed that heteroaggregates containing anti-Fc receptor (Fc gamma R) antibody cross-linked to a second antibody bind to Fc gamma R on ADCC effectors and cause them to kill target cells bearing antigen recognized by the second antibody. The present studies use anti-T3-containing heteroaggregates to re-target human Tc cells to cells for which we have appropriate antibodies, including xenogeneic tumour cells and chicken erythrocytes. These results extend previous observations on the role of T3 in triggering cytotoxicity and suggest that effector cell re-targeting could be used for in vivo treatment of neoplasms and other pathogens that express distinctive surface antigens.

Integrity signals

Registry

Crossref · 10.1038/316354a0

Cites

23 of 23 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The potential of using bispecific antibodies to retarget effector cells toward tumor cells was demonstrated in the 1980s.
“The potential of using bispecific antibodies to retarget effector cells toward tumor cells was demonstrated in the 1980s 3,6,7”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [7]

Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors.
Unkeless, J. C. (1979) · The Journal of Experimental Medicine · doi:10.1084/jem.150.3.580 · Cited by 1,271 · see citing works
OKT3: A monoclonal anti-human T lymphocyte antibody with potent mitogenic properties
Wauwe, J. P. V., DeMay, J., & Goossens, J. G. (1980) · The Journal of Immunology · doi:10.4049/jimmunol.125.5.2359.a · Cited by 712 · see citing works
OKT3: a monoclonal anti-human T lymphocyte antibody with potent mitogenic properties.
Wauwe, J. P. V., De Mey, J., & Goossens, J. (1980) · The Journal of Immunology · doi:10.4049/jimmunol.124.6.2708 · Cited by 588 · see citing works
Hybrid antibodies can target sites for attack by T cells
Staerz, U. D., Kanagawa, O., & Bevan, M. J. (1985) · Nature · doi:10.1038/314628a0 · Cited by 492 · see citing works
Antigen-like effects of monoclonal antibodies directed at receptors on human T cell clones.
Meuer, S. C., Hodgdon, J. C., Hussey, R. E., Protentis, J. P., Schlossman, S. F., & Reinherz, E. L. (1983) · The Journal of Experimental Medicine · doi:10.1084/jem.158.3.988 · Cited by 423 · see citing works
The Major Histocompatibility Complex-Restricted Antigen Receptor on T Cells
HASKINS, K. M., Kappler, J. W., & Marrack, P. (1984) · Annual Review of Immunology · doi:10.1146/annurev.iy.02.040184.000411 · Cited by 366 · see citing works
Evidence for a new segregant series of B cell antigens that are encoded in the HLA-D region and that stimulate secondary allogenic proliferative and cytotoxic responses.
Shaw, S., Johnson, A. H., & Shearer, G. M. (1980) · The Journal of Experimental Medicine · doi:10.1084/jem.152.3.565 · Cited by 347 · see citing works
Self-citation
The Human T-Cell Receptor
Meuer, S. C., Acuto, O., Hercend, T., Schlossman, S. F., & Reinherz, E. L. (1984) · Annual Review of Immunology · doi:10.1146/annurev.iy.02.040184.000323 · Cited by 233 · see citing works
Selective inhibition of human T cell cytotoxicity at levels of target recognition or initiation of lysis by monoclonal OKT3 and Leu-2a antibodies.
Landegren, U. D., Ramstedt, U., Axberg, I., Ullberg, M., Jondal, M., & Wigzell, H. (1982) · The Journal of Experimental Medicine · doi:10.1084/jem.155.5.1579 · Cited by 180 · see citing works
Attachment of an anti-receptor antibody to non-target cells renders them susceptible to lysis by a clone of cytotoxic T lymphocytes.
Kranz, D. M., Tonegawa, S., & Eisen, H. N. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.24.7922 · Cited by 177 · see citing works
Production of target-specific effector cells using hetero-cross-linked aggregates containing anti-target cell and anti-Fc gamma receptor antibodies.
Karpovsky, B., Titus, J. A., Stephany, D. A., & Segal, D. M. (1984) · The Journal of experimental medicine · doi:10.1084/jem.160.6.1686 · Cited by 162 · see citing works
Self-citation
The Human T Cell Receptor: Analysis with Cytotoxic T Cell Clones
Reinherz, E. L., Meuer, S. C., & Schlossman, S. F. (1983) · Immunological Reviews · doi:10.1111/j.1600-065x.1983.tb01085.x · Cited by 159 · see citing works
Fc receptors for mouse IgG1 on human monocytes: polymorphism and role in antibody-induced T cell proliferation.
Tax, W. J. M., Hermes, F. F. M., Willems, R., Capel, P. J., & Koene, R. A. P. (1984) · The Journal of Immunology · doi:10.4049/jimmunol.133.3.1185 · Cited by 156 · see citing works
Possible involvement of the T4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of CTL-target cell binding.
Biddison, W. E., Rao, P. E., Talle, M. A., Goldstein, G., & Shaw, S. (1984) · The Journal of Experimental Medicine · doi:10.1084/jem.159.3.783 · Cited by 152 · see citing works
Self-citation
Human T lymphocyte proliferation induced by a pan-T monoclonal antibody (anti-Leu 4): heterogeneity of response is a function of monocytes.
Kaneoka, H., Pérez-Rojas, G., Sasasuki, T., Benike, C. J., & Engleman, E. G. (1983) · The Journal of Immunology · doi:10.4049/jimmunol.131.1.158 · Cited by 136 · see citing works
Human gamma interferon production by leukocytes induced with monoclonal antibodies recognizing T cells.
von Wussow, P., Platsoucas, C. D., Wiranowska-Stewart, M., & Stewart, W. E. (1981) · The Journal of Immunology · doi:10.4049/jimmunol.127.3.1197 · Cited by 84 · see citing works
Molecular interactions in human T cell-mediated cytotoxicity to EBV II. Monoclonal antibody OKT3 inhibits a post-killer-target recognition/adhesion step.
Tsoukas, C. D., Carson, D. A., Fong, S., & Vaughan, J. H. (1982) · The Journal of Immunology · doi:10.4049/jimmunol.129.4.1421 · Cited by 69 · see citing works
Dimers and trimers of immunoglobulin G covalently cross-linked with a bivalent affinity label
Segal, D. M., & Hurwitz, E. (1976) · Biochemistry · doi:10.1021/bi00669a009 · Cited by 59 · see citing works
Self-citation
Cell Surface Structures Involved in T Cell Activation
Lancki, D. W., Ma, D. I., Havran, W. L., & Fitch, F. W. (1984) · Immunological Reviews · doi:10.1111/j.1600-065x.1984.tb01105.x · Cited by 57 · see citing works
Susceptibility of cytotoxic T lymphocyte (CTL) clones to inhibition by anti-T3 and anti-T4 (but not anti-LFA-1) monoclonal antibodies varies with the "avidity" of CTL-target interaction.
Shaw, S., Goldstein, G., Springer, T. A., & Biddison, W. E. (1985) · The Journal of Immunology · doi:10.4049/jimmunol.134.5.3019 · Cited by 50 · see citing works
Self-citation
Quantitative measurements of the specificity and kinetics of conjugate formation between cloned cytotoxic T lymphocytes and splenic target cells by dual parameter flow cytometry.
Pérez, P., Bluestone, J. A., Stephany, D., & Segal, D. M. (1985) · The Journal of Immunology · doi:10.4049/jimmunol.134.1.478 · Cited by 49 · see citing works
Self-citation
Modulation induction of the T3 antigen by OKT3 antibody is monocyte dependent.
Kan, E. A. R., Platzer, E., Welte, K., & Wang, C. Y. (1984) · The Journal of Immunology · doi:10.4049/jimmunol.133.6.2979 · Cited by 45 · see citing works
Fc (IgG) receptor distributions in homogeneous and heterogeneous cell populations by flow microfluorometry.
Titus, J. A., Sharrow, S. O., Connolly, J. M., & Segal, D. M. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.1.519 · Cited by 26 · see citing works
Self-citation

Flagged first, then by citations

Sorted by citations

Bispecific antibodies: a mechanistic review of the pipeline
Labrijn, A. F., Janmaat, M. L., Reichert, J. M., & Parren, P. W. H. I. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0028-1 · Cited by 1,303 · see citing works
Bispecific T‐cell engagers for cancer immunotherapy
Huehls, A. M., Coupet, T. A., & Sentman, C. L. (2014) · Immunology and Cell Biology · doi:10.1038/icb.2014.93 · Cited by 469 · see citing works
Emerging new therapeutic antibody derivatives for cancer treatment
Jin, S., Sun, Y., Xiao, L., Gu, X., Ning, J., Xu, Y., Chen, S., & Pan, L. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00868-x · Cited by 461 · see citing works
Cytotoxicity mediated by human Fc receptors for IgG
Fanger, M. W., Shen, L., Graziano, R. F., & Guyre, P. M. (1989) · Immunology Today · doi:10.1016/0167-5699(89)90234-x · Cited by 373 · see citing works
A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity.
Mack, M., Riethmüller, G., & Kufer, P. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.15.7021 · Cited by 351 · see citing works
Bispecific antibodies for cancer therapy: The light at the end of the tunnel?
Chames, P., & Baty, D. (2009) · mAbs · doi:10.4161/mabs.1.6.10015 · Cited by 336 · see citing works
New protein engineering approaches to multivalent and bispecific antibody fragments
Plückthun, A., & Pack, P. (1997) · Immunotechnology · doi:10.1016/s1380-2933(97)00067-5 · Cited by 322 · see citing works
Bispecific antibodies: design, therapy, perspectives
Sedykh, S. E., Prinz, V. Y., Buneva, V. N., & Nevinsky, G. A. (2018) · Drug Design Development and Therapy · doi:10.2147/dddt.s151282 · Cited by 292 · see citing works
Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies
Tian, Z., Liu, M., Zhang, Y., & Wang, X. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01084-4 · Cited by 288 · see citing works
Structure, Function, And Serology Of The T-Cell Antigen Receptor Complex
Allison, J. P., & Lanier, L. L. (1987) · Annual Review of Immunology · doi:10.1146/annurev.immunol.5.1.503 · Cited by 269 · see citing works
Multispecific drugs herald a new era of biopharmaceutical innovation
Deshaies, R. J. (2020) · Nature · doi:10.1038/s41586-020-2168-1 · Cited by 262 · see citing works
Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and the Fc receptor gamma chain.
Hwu, P., Shafer, G., Treisman, J. S., Schindler, D. G., Gross, G., Cowherd, R., Rosenberg, S. A., & Eshhar, Z. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.178.1.361 · Cited by 257 · see citing works
Cytotoxicity with target DNA breakdown by rat basophilic leukemia cells expressing both cytolysin and granzyme A
Shiver, J. W., Su, L., & Henkart, P. A. (1992) · Cell · doi:10.1016/0092-8674(92)90359-k · Cited by 235 · see citing works
Hybrid hybridoma producing a bispecific monoclonal antibody that can focus effector T-cell activity.
Staerz, U. D., & Bevan, M. J. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.5.1453 · Cited by 208 · see citing works
The use of hybrid hybridomas to target human cytotoxic T lymphocytes
Lanzavecchia, A., & Scheidegger, D. (1987) · European Journal of Immunology · doi:10.1002/eji.1830170118 · Cited by 198 · see citing works
Bispecific T-cell engagers: Towards understanding variables influencing the in vitro potency and tumor selectivity and their modulation to enhance their efficacy and safety
Ellerman, D. A. (2018) · Methods · doi:10.1016/j.ymeth.2018.10.026 · Cited by 197 · see citing works
SEEDbodies: fusion proteins based on strand-exchange engineered domain (SEED) CH3 heterodimers in an Fc analogue platform for asymmetric binders or immunofusions and bispecific antibodies†
Davis, J. H., Aperlo, C., Li, Y., Kurosawa, E., Lan, Y., Lo, K.-M., & Huston, J. S. (2010) · Protein Engineering Design and Selection · doi:10.1093/protein/gzp094 · Cited by 194 · see citing works
Bispecific and multispecific antibodies in oncology: opportunities and challenges
Goebeler, M.-E., Stuhler, G., & Bargou, R. C. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00905-y · Cited by 191 · see citing works
Bispecific antibody based therapeutics: Strengths and challenges
Thakur, A. B., Huang, M. T. F., & Lum, L. G. (2018) · Blood Reviews · doi:10.1016/j.blre.2018.02.004 · Cited by 183 · see citing works
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.
Valone, F. H., Kaufman, P. A., Guyre, P. M., Lewis, L. D., Memoli, V. A., Deo, Y. M., Graziano, R. F., Fisher, J. L., Meyer, L. A., & Mrozek-Orlowski, M. (1995) · Journal of Clinical Oncology · doi:10.1200/jco.1995.13.9.2281 · Cited by 180 · see citing works
Development of humanized bispecific antibodies reactive with cytotoxic lymphocytes and tumor cells overexpressing the HER2 protooncogene.
Shalaby, M. R., Shepard, H. M., Presta, L. G., Rodrigues, M. L., Beverley, P. C. L., Feldmann, M., & Carter, P. M. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.175.1.217 · Cited by 176 · see citing works
Bi-specific and tri-specific antibodies- the next big thing in solid tumor therapeutics
Runcie, K. D., Budman, D. R., John, V. S., & Seetharamu, N. (2018) · Molecular Medicine · doi:10.1186/s10020-018-0051-4 · Cited by 161 · see citing works
Bispecific antibodies in cancer therapy
Segal, D. M., Weiner, G. J., & Weiner, L. M. (1999) · Current Opinion in Immunology · doi:10.1016/s0952-7915(99)00015-1 · Cited by 161 · see citing works
Self-citation
A revival of bispecific antibodies
Kufer, P., Lutterbüse, R., & Baeuerle, P. A. (2004) · Trends in Biotechnology · doi:10.1016/j.tibtech.2004.03.006 · Cited by 157 · see citing works
Cure of Xenografted Human Tumors by Bispecific Monoclonal Antibodies and Human T Cells
Renner, C., Jung, W. E., Şahin, U., Denfeld, R. W., Pohl, C., Trümper, L. H. P., Hartmann, F., Diehl, V., van Lier, R. A. W., & Pfreundschuh, M. G. (1994) · Science · doi:10.1126/science.8171337 · Cited by 156 · see citing works
T cell engaging bispecific antibody (T-BsAb): From technology to therapeutics
Wu, Z., & Cheung, N. V. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.08.005 · Cited by 151 · see citing works
Synergistic roles of granzymes A and B in mediating target cell death by rat basophilic leukemia mast cell tumors also expressing cytolysin/perforin.
Nakajima, H., Park, H. L., & Henkart, P. A. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.3.1037 · Cited by 146 · see citing works
Development of therapeutic antibodies for the treatment of diseases
Wang, Z., Wang, G., Lu, H., Li, H., Tang, M., & Tong, A. (2022) · Molecular Biomedicine · doi:10.1186/s43556-022-00100-4 · Cited by 136 · see citing works
Bispecific T-Cell Redirection versus Chimeric Antigen Receptor (CAR)-T Cells as Approaches to Kill Cancer Cells
Strohl, W. R., & Naso, M. F. (2019) · Antibodies · doi:10.3390/antib8030041 · Cited by 136 · see citing works
Measurement of cytotoxicity by target cell release and retention of the fluorescent dye bis-carboxyethyl-carboxyfluorescein (BCECF)
Kolber, M. A., Quinones, R., Gress, R. E., & Henkert, P. A. (1988) · Journal of Immunological Methods · doi:10.1016/0022-1759(88)90427-9 · Cited by 132 · see citing works
Mono‐ and Bivalent Antibody Fragments Produced in Escherichia coli: Engineering, Folding and Antigen Binding
Plückthun, A. (1992) · Immunological Reviews · doi:10.1111/j.1600-065x.1992.tb01525.x · Cited by 132 · see citing works
The First Bagshawe lecture: Towards generating cytotoxic agents at cancer sites
Bagshawe, K. D. (1989) · British Journal of Cancer · doi:10.1038/bjc.1989.270 · Cited by 131 · see citing works
Efficient tumor killing and minimal cytokine release with novel T-cell agonist bispecific antibodies
Trinklein, N. D., Pham, D. T., Schellenberger, U., Buelow, B. D., Boudreau, A. A., Choudhry, P., Clarke, S., Dang, K. H., Harris, K. E., Iyer, S., et al. (2019) · mAbs · doi:10.1080/19420862.2019.1574521 · Cited by 109 · see citing works
Bispecific Antibodies for Multiple Myeloma: A Review of Targets, Drugs, Clinical Trials, and Future Directions
Caraccio, C., Krishna, S., Phillips, D. J., & Schürch, C. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00501 · Cited by 106 · see citing works
Potent antitumour activity of a new class of tumour-specific killer cells
Chen, S. Y., Yang, A., Chen, J.-D., Kute, T. E., King, C. R., Collier, J., Cong, Y., Yao, C., & Huang, X. F. (1997) · Nature · doi:10.1038/385078a0 · Cited by 105 · see citing works
T-cell-receptor-independent activation of cytolytic activity of cytotoxic T lymphocytes mediated through CD44 and gp90MEL-14.
Seth, A., Goté, L. R., Nagarkatti, M., & Nagarkatti, P. S. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.17.7877 · Cited by 105 · see citing works
Immunomodulators in Clinical Medicine
Fauci, A. S., Rosenberg, S. A., SHERWIN, S. A., Dinarello, C. A., LONGO, D. L., & LANE, H. C. (1987) · Annals of Internal Medicine · doi:10.7326/0003-4819-106-3-421 · Cited by 104 · see citing works
Rationale for Combining Bispecific T Cell Activating Antibodies With Checkpoint Blockade for Cancer Therapy
Kobold, S., Pantelyushin, S., Rataj, F., & Berg, J. V. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00285 · Cited by 103 · see citing works
A noncytotoxic mast cell tumor line exhibits potent IgE-dependent cytotoxicity after transfection with the cytolysin/perforin gene
Shiver, J. W., & Henkart, P. A. (1991) · Cell · doi:10.1016/0092-8674(91)90272-z · Cited by 101 · see citing works
Breast cancer immunotherapy: Current and novel approaches
Barzaman, K., Moradi‐Kalbolandi, S., Hosseinzadeh, A., Kazemi, M. H., Khorramdelazad, H., Safari, E., & Farahmand, L. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107886 · Cited by 100 · see citing works
Monoclonal antibody-targeted superantigens: a different class of anti-tumor agents.
Dohlsten, M., Hedlund, G., Akerblom, E. B., Lando, P. A., & Kalland, T. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.20.9287 · Cited by 99 · see citing works
Antiviral Cytotoxic T Lymphocyte Induction and Vaccination
Rouse, B. T., Norley, S., & Martin, S. J. (1988) · Clinical Infectious Diseases · doi:10.1093/clinids/10.1.16 · Cited by 97 · see citing works
Coming-of-Age of Antibodies in Cancer Therapeutics
Ayyar, B. V., Arora, S., & O’Kennedy, R. J. (2016) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.09.005 · Cited by 96 · see citing works
Functional balance between T cell chimeric receptor density and tumor associated antigen density: CTL mediated cytolysis and lymphokine production
Weijtens, M. E. M., Hart, E., & Bolhuis, R. L. H. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301051 · Cited by 95 · see citing works
Specific targeting of human peripheral blood T cells by heteroaggregates containing anti-T3 crosslinked to anti-target cell antibodies.
Pérez, P., Hoffman, R. W., Titus, J. A., & Segal, D. M. (1986) · The Journal of Experimental Medicine · doi:10.1084/jem.163.1.166 · Cited by 91 · see citing works
Self-citation
Antibodies and gene therapy: teaching old ‘magic bullets’ new tricks
Sanz, L., Blanco, B., & Álvarez‐Vallina, L. (2003) · Trends in Immunology · doi:10.1016/j.it.2003.12.001 · Cited by 90 · see citing works
Bispecific Antibodies for the Treatment of Acute Myeloid Leukemia
Guy, D. G., & Uy, G. L. (2018) · Current Hematologic Malignancy Reports · doi:10.1007/s11899-018-0472-8 · Cited by 88 · see citing works
Bispecific antibodies engage T cells for antitumor immunotherapy
Choi, B. D., Cai, M., Bigner, D. D., Mehta, A. I., Kuan, C.-T., & Sampson, J. H. (2011) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2011.572874 · Cited by 88 · see citing works
Comparison of three different methods for radiolabelling human activated T lymphocytes
Botti, C., Negri, D. R. M., Seregni, E. C., Ramakrishna, V., Arienti, F., Maffioli, L. S., Lombardo, C., Bogni, A., Pascali, C., Crippa, F., et al. (1997) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/bf01267680 · Cited by 88 · see citing works
Bispecific, T-Cell-Recruiting Antibodies in B-Cell Malignancies
Lejeune, M., Köse, M. C., Duray, E., Einsele, H., Beguin, Y. P., & Caers, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00762 · Cited by 87 · see citing works
Caspase Dependence of Target Cell Damage Induced by Cytotoxic Lymphocytes
Sarin, A., Haddad, E. K., & Henkart, P. A. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.6.2810 · Cited by 87 · see citing works
Biologic properties of a bispecific single-chain antibody directed against 17-1A (EpCAM) and CD3: tumor cell-dependent T cell stimulation and cytotoxic activity
Mack, M., Gruber, R., Schmidt, S., Riethmüller, G., & Kufer, P. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.8.3965 · Cited by 86 · see citing works
Symmetry breaking: bispecific antibodies, the beginnings, and 50 years on.
Riethmüller, G. (2012) · Europe PMC (PubMed Central) · Cited by 85 · see citing works
Bispecific antibodies and CARs: generalized immunotherapeutics harnessing T cell redirection
Zhukovsky, E. A., Morse, R. J., & Maus, M. V. (2016) · Current Opinion in Immunology · doi:10.1016/j.coi.2016.02.006 · Cited by 85 · see citing works
Heteroantibody duplexes target cells for lysis by cytotoxic T lymphocytes.
Liu, M., Kranz, D. M., Kurnick, J. T., Boyle, L. A., Levy, R., & Eisen, H. N. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.24.8648 · Cited by 82 · see citing works
Induction of tumor‐cell lysis by bi‐specific monoclonal antibodies recognizing renal‐cell carcinoma and cd3 antigen
Duk, J. V., Warnaar, S. O., van Eendenburg, J. D. H., Thienpont, M., Braakman, E., Boot, J. H., Fleuren, G. J., & Bolhuis, R. L. H. (1989) · International Journal of Cancer · doi:10.1002/ijc.2910430230 · Cited by 81 · see citing works
Checkpoint Antibodies but not T Cell–Recruiting Diabodies Effectively Synergize with TIL-Inducing γ-Irradiation
Hettich, M., Lahoti, J., Prasad, S., & Niedermann, G. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-3451 · Cited by 78 · see citing works
The first constant domain (CH1 and CL) of an antibody used as heterodimerization domain for bispecific miniantibodies
Müller, K. M., Arndt, K. M., Strittmatter, W., & Plückthun, A. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00021-0 · Cited by 78 · see citing works
Advances in bispecific biotherapeutics for the treatment of cancer
May, C., Sapra, P., & Gerber, H. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.07.011 · Cited by 77 · see citing works
Bispecific monoclonal antibodies for targeted immunotherapy of solid tumors: Recent advances and clinical trials
Hosseini, S. S., Khalili, S., Baradaran, B., Bidar, N., Shahbazi, M., Mosafer, J., Hashemzaei, M., Mokhtarzadeh, A., & Hamblin, M. R. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.11.058 · Cited by 76 · see citing works
Vaccine and antibody-directed T cell tumour immunotherapy
Dermime, S., Gilham, D. E., Shaw, D. M., Davidson, E. J., Meziane, E. K., Armstrong, A. C., Hawkins, R. E., & Stern, P. L. (2004) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2004.03.002 · Cited by 74 · see citing works
Human ovarian carcinoma lysis by cytotoxic t cells targeted by bispecific monoclonal antibodies: Analysis of the antibody components
Mezzanzanica, D., Canevari, S., Ménard, S., Pupa, S. M., Tagliabue, E., Lanzavecchia, A., & COLNAGHI, M. I. (1988) · International Journal of Cancer · doi:10.1002/ijc.2910410422 · Cited by 74 · see citing works
Targeting CLDN18.2 by CD3 Bispecific and ADC Modalities for the Treatments of Gastric and Pancreatic Cancer
Zhu, G., Foletti, D. L., Liu, X., Ding, S., Witt, J. M., Hasa-Moreno, A., Rickert, M., Holz, C., Aschenbrenner, L. M., Yang, A. H., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-44874-0 · Cited by 73 · see citing works
Induction of cytotoxicity in resting human T lymphocytes bound to tumor cells by antibody heteroconjugates.
Jung, G., Ledbetter, J. A., & Müller‐Eberhard, H. J. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.13.4611 · Cited by 73 · see citing works
Hexavalent bispecific antibodies represent a new class of anticancer therapeutics: 1. Properties of anti-CD20/CD22 antibodies in lymphoma
Rossi, E. A., Goldenberg, D. M., Cardillo, T. M., Stein, R., & Chang, C. (2009) · Blood · doi:10.1182/blood-2008-10-187138 · Cited by 72 · see citing works
Bispecific single chain molecules (Janusins) target cytotoxic lymphocytes on HIV infected cells.
Traunecker, A., Lanzavecchia, A., & Karjalainen, K. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb04932.x · Cited by 67 · see citing works
Activation of peripheral blood T cells via the p75 interleukin 2 receptor.
Yagita∥, H., Nakata, M., Azuma, A., Nitta, T., Takeshita, T., Sugamura, K., & Okumura, K. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.170.4.1445 · Cited by 66 · see citing works
Highly lytic CD8+, alpha beta T-cell receptor cytotoxic T cells with major histocompatibility complex (MHC) class I antigen-directed cytotoxicity in beta 2-microglobulin, MHC class I-deficient mice.
Apasov, S. G., & Sitkovsky, M. V. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.7.2837 · Cited by 65 · see citing works
Pharmacokinetics, biodistribution and biological effects of intravenously administered bispecific monoclonal antibody OC/TR F(ab′)2 in ovarian carcinoma patients
Tibben, J. G., Boerman, O. C., Massuger, L. F. A. G., Schijf, C. P. T., Claessens, R. A. M. J., & Corstens, F. H. M. (1996) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19960516)66:4 · Cited by 60 · see citing works
Target cell‐induced T cell activation with bi‐ and trispecific antibody fragments
Jung, G., Freimann, U., von Marschall, Z., Reisfeld, R. A., & Wilmanns, W. (1991) · European Journal of Immunology · doi:10.1002/eji.1830211020 · Cited by 61 · see citing works
Lymphokine-activated killer activity in long-term cultures with anti-CD3 plus interleukin 2: identification and isolation of effector subsets.
Ochoa, A. C., Hasz, D. E., Rezonzew, R., Anderson, P. M., & Bach, F. H. (1989) · PubMed · Cited by 61 · see citing works
Activation of human peripheral blood mononuclear cells by anti-T3: killing of tumor target cells coated with anti-target-anti-T3 conjugates.
Jung, G., Honsik, C., Reisfeld, R., & Müller‐Eberhard, H. J. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.12.4479 · Cited by 60 · see citing works
Genetic engineering of T cell specificity for immunotherapy of cancer
Willemsen, R. A., Debets, R., Chames, P., & Bolhuis, R. L. H. (2002) · Human Immunology · doi:10.1016/s0198-8859(02)00730-9 · Cited by 59 · see citing works
Stepping forward: T-cell redirecting bispecific antibodies in cancer therapy
Qin, X., Ning, W., Liu, H., Liu, X., Luo, W., & Xia, N. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.03.027 · Cited by 59 · see citing works
Antibodies from Escherichia coli
Plückthun, A. (1990) · Nature · doi:10.1038/347497a0 · Cited by 58 · see citing works
BiTEs, DARTS, BiKEs and TriKEs—Are Antibody Based Therapies Changing the Future Treatment of AML?
Allen, C., Zeidan, A. M., & Bewersdorf, J. P. (2021) · Life · doi:10.3390/life11060465 · Cited by 57 · see citing works
Tumor Therapy by Immune Recruitment with Bispecific Antibodies
Renner, C., & Pfreundschuh, M. (1995) · Immunological Reviews · doi:10.1111/j.1600-065x.1995.tb00082.x · Cited by 58 · see citing works
Ertumaxomab: a trifunctional antibody for breast cancer treatment
Kiewe, P. M., & Thiel, E. (2008) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.17.10.1553 · Cited by 56 · see citing works
Characterization of a Bispecific FLT3 X CD3 Antibody in an Improved, Recombinant Format for the Treatment of Leukemia
Durben, M., Schmiedel, D., Hofmann, M., Vogt, F., Nuebling, T., Pyż, E., Bühring, H., Rammensee, H., Salih, H. R., Große‐Hovest, L., et al. (2015) · Molecular Therapy · doi:10.1038/mt.2015.2 · Cited by 56 · see citing works
Engineering multi-specific antibodies against HIV-1
Padte, N. N., Yu, J., Huang, Y., & Ho, D. D. (2018) · Retrovirology · doi:10.1186/s12977-018-0439-9 · Cited by 56 · see citing works
T-cell based cancer immunotherapy: direct or redirected tumor-cell recognition?
Beun, G. D. M., van de Velde, C. J. �., & Fleuren, G. J. (1994) · Immunology Today · doi:10.1016/0167-5699(94)90019-1 · Cited by 55 · see citing works
Bifunctional antibodies: concept, production and applications
Nolan, O., & O’Kennedy, R. J. (1990) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/0167-4838(90)90139-7 · Cited by 55 · see citing works
Potent inhibition of local and disseminated tumor growth in immunocompetent mouse models by a bispecific antibody construct specific for Murine CD3
Schlereth, B., Kleindienst, P., Fichtner, I., Lorenczewski, G., Brischwein, K., Lippold, S., da Silva, A., Locher, M., Kischel, R., Lutterbüse, R., et al. (2005) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-005-0082-x · Cited by 54 · see citing works
Bispecific Antibodies and Trispecific Immunocytokines for Targeting the Immune System Against Cancer
Fournier, P., & Schirrmacher, V. (2012) · BioDrugs · doi:10.1007/s40259-012-0008-z · Cited by 52 · see citing works
Use of heteropolymeric monoclonal antibodies to attach antigens to the C3b receptor of human erythrocytes: a potential therapeutic treatment.
Taylor, R. P., Sutherland, W. M., Reist, C. J., Webb, D. J., Wright, E. L., & Labuguen, R. H. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.8.3305 · Cited by 52 · see citing works
Hormone Conjugated with Antibody to CD3 Mediates Cytotoxic T Cell Lysis of Human Melanoma Cells
Liu, M. A., Nussbaum, S. R., & Eisen, H. N. (1988) · Science · doi:10.1126/science.3257303 · Cited by 52 · see citing works
Construction and biological activity of a recombinant bispecific single-chain antibody designed for therapy of minimal residual colorectal cancer
Kufer, P., Mack, M., Gruber, R., Lutterbüse, R., Zettl, F., & Riethmüller, G. (1997) · Cancer Immunology Immunotherapy · doi:10.1007/s002620050431 · Cited by 51 · see citing works
Targeting of Cytotoxic Cells with Heterocrosslinked Antibodies
Segal, D. M., & Wunderlich, J. R. (1988) · Cancer Investigation · doi:10.3109/07357908809077031 · Cited by 49 · see citing works
Self-citation
Unleashing the clinical power of T cells: CD19/CD3 bi-specific T cell engager (BiTE®) antibody construct blinatumomab as a potential therapy
Zimmerman, Z. F., Maniar, T. N., & Nagorsen, D. (2014) · International Immunology · doi:10.1093/intimm/dxu089 · Cited by 48 · see citing works
SITE-SPECIFIC FUNCTIONALIZATION OF PROTEINS AND THEIR APPLICATIONS TO THERAPEUTIC ANTIBODIES
van Vught, R., Pieters, R. J., & Breukink, E. J. (2014) · Computational and Structural Biotechnology Journal · doi:10.5936/csbj.201402001 · Cited by 47 · see citing works
Bispecific F(ab′)2 monomer prepared with anti‐CD3 and anti‐tumor monoclonal antibodies is most potent in induction of cytolysis of human T cells
Nitta, T., Yagita∥, H., Azuma, T., Kiyoshi, S. A. T. O., & Okumura, K. (1989) · European Journal of Immunology · doi:10.1002/eji.1830190814 · Cited by 47 · see citing works
Overweight as an avoidable cause of cancer in Europe
Bergström, A., Pisani, P., Tenet, V., Wolk, A., & Adami, H. (2001) · International Journal of Cancer · doi:10.1002/1097-0215(200002)9999:9999 · Cited by 772 · see citing works
Bispecific Antibody Targeted T Cell Therapy of Ovarian Cancer: Clinical Results and Future Directions
Canevari, S., Mezzanzanica, D., Mazzoni, A., Negri, D. R. M., Ramakrishna, V., Bolhuis, R. L. H., COLNAGHI, M. I., & Bolis, G. (1995) · Journal of Hematotherapy · doi:10.1089/scd.1.1995.4.423 · Cited by 47 · see citing works
Targeting T Cells with Bispecific Antibodies for Cancer Therapy
Lum, L. G., & Thakur, A. B. (2011) · BioDrugs · doi:10.2165/11595950-000000000-00000 · Cited by 46 · see citing works
Recent Advances in the Molecular Design and Applications of Multispecific Biotherapeutics
Zhong, X., & D’Antona, A. M. (2021) · Antibodies · doi:10.3390/antib10020013 · Cited by 45 · see citing works
Visualization of effective tumor targeting by CD8+ natural killer T cells redirected with bispecific antibody F(ab')(2)HER2xCD3.
Scheffold, C., Kornacker, M., Scheffold, Y. C., Contag, C. H., & Negrin, R. S. (2002) · PubMed · Cited by 45 · see citing works
Chimeric scFv/γ receptor-mediated T-cell lysis of tumor cells is coregulated by adhesion and accessory molecules
Weijtens, M. E. M., Willemsen, R. A., Krimpen, B. A. V., & Bolhuis, R. L. H. (1998) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19980717)77:2 · Cited by 45 · see citing works
The promise of bispecific antibodies: Clinical applications and challenges
Lim, S. M., Pyo, K., Soo, R. A., & Cho, B. C. (2021) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2021.102240 · Cited by 45 · see citing works
Localization of monoclonal antibody G250 and bispecific monoclonal antibody CD3/G250 in human renal‐cell carcinoma xenografts: Relative effects of size and affinity
van Dijk, J., Zegveld, S. T., Fleuren, G. J., & Warnaar, S. O. (1991) · International Journal of Cancer · doi:10.1002/ijc.2910480518 · Cited by 44 · see citing works
Molecular checkpoints controlling natural killer cell activation and their modulation for cancer immunotherapy
Kwon, H.-J., Kim, N., & Kim, H. S. (2017) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.42 · Cited by 43 · see citing works

Specific targeting of human peripheral blood T cells by heteroaggregates containing anti-T3 crosslinked to anti-target cell antibodies.
Pérez, P., Hoffman, R. W., Titus, J. A., & Segal, D. M. (1986) · The Journal of Experimental Medicine · doi:10.1084/jem.163.1.166 · Cited by 91 · see citing works
Self-citation
Specific lysis of human tumor cells by T cells coated with anti-T3 cross-linked to anti-tumor antibody.
Pérez, P., Titus, J. A., Lotze, M. T., Cuttitta, F., Longo, D. L., Groves, E. S., Rabin, H. R., Durda, P. J., & Segal, D. M. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.137.7.2069 · Cited by 72 · see citing works
Self-citation
Anti-T3 antibody both activates and inhibits the cytotoxic activity of human T cell clones.
Hoffman, R. W., Quinones, R., & Shaw, S. (1985) · PubMed · Cited by 1 · see citing works
Self-citation
Targeting of cytotoxic cells against tumors with heterocrosslinked, bispecific antibodies.
Segal, D. M., Qian, J. H., Garrido, M. A., Perez, P., Winkler, D. F., Wunderlich, J. R., Snider, D. P., Valdayo, M. J., & Titus, J. A. (1988) · PubMed · Cited by 5 · see citing works
Self-citation
Induction of nonspecific cytotoxicity by monoclonal anti-T3 antibodies.
Leeuwenberg, J. F. M., Spits, H., Tax, W. J. M., & Capel, P. J. (1985) · The Journal of Immunology · doi:10.4049/jimmunol.134.6.3770 · Cited by 126 · see citing works

Authors: Perez, P., Hoffman, R. W., Shaw, S., Bluestone, J. A., & Segal, D. M.
Affiliations: National Institutes of Health (US)
ORCID: Shaw, Stephen
Bluestone, Jeffrey A.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1985-07
Volume: 316
Issue: 6026
Pages: 354-356
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/316354a0
OpenAlex: W2065272367
Cited by: 337
References: 23
Citations by year: 2026: 4 · 2024: 10 · 2023: 7 · 2022: 7 · 2021: 17 · 2020: 9 · 2019: 7 · 2018: 10 · 2017: 6 · 2016: 6 · 2015: 4 · 2014: 11 · 2013: 6 · 2012: 6
FWCI: 22.63
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: cytotoxic T lymphocytes, T cell receptor, antibody-dependent cellular cytotoxicity, heteroaggregates, T cell specificity, chicken erythrocytes, T cell cytotoxicity
MeSH terms: Animals, Antibodies, Antibodies, Monoclonal, Antibody Specificity, Antibody-Dependent Cell Cytotoxicity, Antigens, Surface, Clone Cells, Glycoproteins, Histocompatibility Antigens, Humans, Receptors, Antigen, T-Cell, T-Lymphocytes, Cytotoxic, CD3 Complex, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Specific targeting of cytotoxic T cells by anti-T3 linked to anti-target cell antibody

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks