Bispecific Antibodies for Cancer Immunotherapy: Current Perspectives

Tumour necrosis factor and cancer

Balkwill, F. R. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2628 · Cited by 1,925 · see citing works

Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody

Bargou, R., Leo, E., Zugmaier, G., Klinger, M., Goebeler, M., Knop, S., Noppeney, R., Viardot, A., Hess, G., Schuler, M., et al. (2008) · Science · doi:10.1126/science.1158545 · Cited by 1,078 · see citing works

Immunostimulatory monoclonal antibodies for cancer therapy

Melero, I., Hervás‐Stubbs, S., Glennie, M. J., Pardoll, D. M., & Chen, L. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2051 · Cited by 626 · see citing works

PEGylated antibodies and antibody fragments for improved therapy: a review

Chapman, A. P. (2002) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00026-1 · Cited by 558 · see citing works

Variants of the Antibody Herceptin That Interact with HER2 and VEGF at the Antigen Binding Site

Boström, J., Yu, S., Kan, D., Appleton, B. A., Lee, C. V., Billeci, K. L., Man, W., Peale, F. V., Jr., Ross, S., Wiesmann, C., et al. (2009) · Science · doi:10.1126/science.1165480 · Cited by 372 · see citing works

Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin

Wu, C., Hua, Y., Grinnell, C. M., Bryant, S. H., Miller, R., Clabbers, A., Bose, S., McCarthy, D., Zhu, R.-R., Santora, L. C., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1345 · Cited by 344 · see citing works

Engineered protein scaffolds as next-generation antibody therapeutics

Gebauer, M., & Skerra, A. (2009) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2009.04.627 · Cited by 339 · 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

Improved tumor targeting of anti–epidermal growth factor receptor Nanobodies through albumin binding: taking advantage of modular Nanobody technology

Tijink, B. M., Laeremans, T., Budde, M., van Walsum, M., Dreier, T., de Haard, H., Leemans, C. R., & van Dongen, G. A. M. S. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-2384 · Cited by 306 · see citing works

Strategies to Extend Plasma Half-Lives of Recombinant Antibodies

Kontermann, R. E. (2009) · BioDrugs · doi:10.2165/00063030-200923020-00003 · Cited by 245 · see citing works

Survival Improvement in Patients With Medullary Thyroid Carcinoma Who Undergo Pretargeted Anti–Carcinoembryonic-Antigen Radioimmunotherapy: A Collaborative Study With the French Endocrine Tumor Group

Chatal, J., Campion, L., Kraeber‐Bodéré, F., Bardet, S., Vuillez, J.-P., Charbonnel, B. H., Rohmer, V., Chang, C., Sharkey, R. M., Goldenberg, D. M., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.04.4917 · Cited by 227 · see citing works

Improved Pharmacokinetics of Recombinant Bispecific Antibody Molecules by Fusion to Human Serum Albumin

Müller, D., Karle, A. C., Meißburger, B., Höfig, I., Stork, R., & Kontermann, R. E. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700820200 · Cited by 222 · see citing works

Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targeting

Rossi, E. A., Goldenberg, D. M., Cardillo, T. M., McBride, W. J., Sharkey, R. M., & Chang, C.-H. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600982103 · Cited by 209 · see citing works

Simultaneous Activation of T Cells and Accessory Cells by a New Class of Intact Bispecific Antibody Results in Efficient Tumor Cell Killing

Zeidler, R., Reisbach, G., Wollenberg, B., Lang, S., Chaubal, S., Schmitt, B., & Lindhofer, H. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.3.1246 · Cited by 204 · see citing works

Phase I Trial of the Trifunctional Anti-HER2 × Anti-CD3 Antibody Ertumaxomab in Metastatic Breast Cancer

Kiewe, P. M., Hasmüller, S., Kahlert, S., Heinrigs, M., Rack, B. K., Marmé, A., Korfel, A., Jäger, M., Lindhofer, H., Sommer, H. L., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2436 · Cited by 198 · see citing works

Anti-serum albumin domain antibodies for extending the half-lives of short lived drugs

Holt, L. J., Basran, A., Jones, K. H., Chorlton, J., Jespers, L. S., Brewis, N., & Tomlinson, I. M. (2008) · Protein Engineering Design and Selection · doi:10.1093/protein/gzm067 · Cited by 193 · see citing works

T Cell Costimulus-Independent and Very Efficacious Inhibition of Tumor Growth in Mice Bearing Subcutaneous or Leukemic Human B Cell Lymphoma Xenografts by a CD19-/CD3- Bispecific Single-Chain Antibody Construct

Dreier, T., Baeuerle, P. A., Fichtner, I., Grün, M., Schlereth, B., Lorenczewski, G., Kufer, P., Lutterbüse, R., Riethmüller, G., Gjorstrup, P., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.8.4397 · Cited by 191 · see citing works

Single-domain antibodies as building blocks for novel therapeutics

Saerens, D., Ghassabeh, G. H., & Muyldermans, S. (2008) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2008.07.006 · Cited by 186 · see citing works

A Fully Human Recombinant IgG-like Bispecific Antibody to Both the Epidermal Growth Factor Receptor and the Insulin-like Growth Factor Receptor for Enhanced Antitumor Activity

Lu, D., Zhang, H., Koo, H., Tonra, J. R., Balderes, P. J., Prewett, M. C., Corcoran, E., Mangalampalli, V. R. M., Bassi, R., Anselma, D. J., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500815200 · Cited by 180 · see citing works

Mode of cytotoxic action of T cell-engaging BiTE antibody MT110

Haas, C., Krinner, E., Brischwein, K., Hoffmann, P., Lutterbüse, R., Schlereth, B., Kufer, P., & Baeuerle, P. A. (2009) · Immunobiology · doi:10.1016/j.imbio.2008.11.014 · Cited by 179 · see citing works

Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody

Ruf, P., & Lindhofer, H. (2001) · Blood · doi:10.1182/blood.v98.8.2526 · Cited by 174 · see citing works

BiTE: Teaching antibodies to engage T-cells for cancer therapy.

Baeuerle, P. A., Kufer, P., & Bargou, R. C. (2009) · PubMed · Cited by 159 · see citing works

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

Handbook of Therapeutic Antibodies

(2007) · Wiley eBooks · doi:10.1002/9783527619740 · Cited by 145 · see citing works

Recombinant bispecific antibodies for cancer therapy

Kontermann, R. E. (2005) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2005.00008.x · Cited by 142 · see citing works

Targeting ErbB2 and ErbB3 with a bispecific single-chain Fv enhances targeting selectivity and induces a therapeutic effect in vitro

Robinson, M. K., Hodge, K. M., Horak, E. M., Sundberg, Å. L., Russeva, M., Shaller, C. C., von Mehren, M., Shchaveleva, I., Simmons, H. H., Marks, J. D., et al. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604700 · Cited by 128 · see citing works

Simultaneous Blockade of Both the Epidermal Growth Factor Receptor and the Insulin-like Growth Factor Receptor Signaling Pathways in Cancer Cells with a Fully Human Recombinant Bispecific Antibody

Lu, D., Zhang, H., Ludwig, D. L., Persaud, A., Jimenez, X., Burtrum, D. B., Balderes, P. J., Liu, M., Böhlen, P., Witte, L., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310132200 · Cited by 124 · see citing works

A novel tri-functional antibody fusion protein with improved pharmacokinetic properties generated by fusing a bispecific single-chain diabody with an albumin-binding domain from streptococcal protein G

Stork, R., Müller, D., & Kontermann, R. E. (2007) · Protein Engineering Design and Selection · doi:10.1093/protein/gzm061 · Cited by 111 · see citing works

Biodistribution of a Bispecific Single-chain Diabody and Its Half-life Extended Derivatives

Stork, R., Campigna, E., Robert, B., Müller, D., & Kontermann, R. E. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.027078 · Cited by 109 · see citing works

T-cell activation and B-cell depletion in chimpanzees treated with a bispecific anti-CD19/anti-CD3 single-chain antibody construct

Schlereth, B., Quadt, C., Dreier, T., Kufer, P., Lorenczewski, G., Prang, N., Brandl, C., Lippold, S., Cobb, K., Brasky, K., et al. (2006) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-005-0001-1 · Cited by 103 · see citing works

Cancer imaging and therapy with bispecific antibody pretargeting

Goldenberg, D. M., Chatal, J., Barbet, J., Boerman, O. C., & Sharkey, R. M. (2007) · Update on Cancer Therapeutics · doi:10.1016/j.uct.2007.04.003 · Cited by 99 · see citing works

Fusion of a recombinant antibody fragment with a homo-amino-acid polymer: effects on biophysical properties and prolonged plasma half-life

Schlapschy, M., Theobald, I., Mack, H. I. D., et al. (2007) · Protein Engineering Design and Selection · doi:10.1093/protein/gzm020 · Cited by 98 · see citing works

N-Glycosylation as Novel Strategy to Improve Pharmacokinetic Properties of Bispecific Single-chain Diabodies

Stork, R., Zettlitz, K. A., Müller, D., Rether, M., Hanisch, F., & Kontermann, R. E. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709179200 · Cited by 97 · see citing works

Recombinant approaches to IgG-like bispecific antibodies

Marvin, J. S., & Zhu, Z. (2005) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2005.00119.x · Cited by 87 · see citing works

Genetic alteration of a bispecific ligand-directed toxin targeting human CD19 and CD22 receptors resulting in improved efficacy against systemic B cell malignancy

Vallera, D. A., Chen, H., Sicheneder, A. R., et al. (2009) · Leukemia Research · doi:10.1016/j.leukres.2009.02.006 · Cited by 87 · see citing works

Recombinant bispecific antibodies for cellular cancer immunotherapy.

Müller, D., & Kontermann, R. E. (2007) · PubMed · Cited by 83 · see citing works

A bispecific diabody directed against prostate-specific membrane antigen and CD3 induces T-cell mediated lysis of prostate cancer cells

Bühler, P., Wolf, P., Gierschner, D., Schaber, I., Katzenwadel, A., Schultze-Seemann, W., Wetterauer, U., Tacke, M., Swamy, M., Schamel, W. W. A., et al. (2008) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-007-0348-6 · Cited by 82 · see citing works

A Novel CD19-directed Recombinant Bispecific Antibody Derivative With Enhanced Immune Effector Functions for Human Leukemic Cells

Kellner, C., Bruenke, J., Stieglmaier, J., et al. (2008) · Journal of Immunotherapy · doi:10.1097/cji.0b013e318186c8b4 · Cited by 78 · see citing works

Potent Control of Tumor Growth by CEA/CD3-bispecific Single-chain Antibody Constructs That Are Not Competitively Inhibited by Soluble CEA

Lutterbuese, R., Raum, T., Kischel, R., Lutterbuese, P., Schlereth, B., Schaller, E., Mangold, S., Rau, D., Meier, P., Kiener, P. A., et al. (2009) · Journal of Immunotherapy · doi:10.1097/cji.0b013e31819b7c70 · Cited by 77 · see citing works

A Novel Bispecific, Trivalent Antibody Construct for Targeting Pancreatic Carcinoma

Gold, D. V., Goldenberg, D. M., Karacay, H., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0232 · Cited by 72 · see citing works

Augmentation of antitumor effects of p53 Gene therapy by combination with HDAC inhibitor

Takimoto, R., Kato, J., Terui, T., et al. (2005) · Cancer Biology & Therapy · doi:10.4161/cbt.4.4.1620 · Cited by 67 · see citing works

Treatment of Malignant Pleural Effusion With the Trifunctional Antibody Catumaxomab (Removab) (Anti-EpCAM×Anti-CD3)

Sebastian, M., Kiewe, P. M., Schuette, W., Brust, D., Peschel, C., Schneller, F., Rühle, K.-H., Nilius, G., Ewert, R., Lodziewski, S., et al. (2009) · Journal of Immunotherapy · doi:10.1097/cji.0b013e318195b5bb · Cited by 65 · see citing works

Engineering and characterization of a bispecific HER2 × EGFR‐binding affibody molecule

Friedman, M., Lindström, S., Ekerljung, L., Svahn, H. A., Carlsson, J., Brismar, H., Gedda, L., Frejd, F. Y., & Ståhl, S. (2009) · Biotechnology and Applied Biochemistry · doi:10.1042/ba20090096 · Cited by 65 · see citing works

A recombinant, fully human, bispecific antibody neutralizes the biological activities mediated by both vascular endothelial growth factor receptors 2 and 3

Jimenez, X., Lu, D., Brennan, L., et al. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-04-0261 · Cited by 64 · see citing works

T cells armed with anti-CD3 × anti-CD20 bispecific antibody enhance killing of CD20+ malignant B cells and bypass complement-mediated rituximab resistance in vitro

Gall, J. M., Davol, P. A., Grabert, R. C., et al. (2005) · Experimental Hematology · doi:10.1016/j.exphem.2005.01.007 · Cited by 63 · see citing works

Antitumor Activity of an EpCAM/CD3-bispecific BiTE Antibody During Long-term Treatment of Mice in the Absence of T-cell Anergy and Sustained Cytokine Release

Amann, M., d’Argouges, S., Lorenczewski, G., Brischwein, K., Kischel, R., Lutterbuese, R., Mangold, S., Rau, D., Volkland, J., Pflanz, S., et al. (2009) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181a1c097 · Cited by 63 · see citing works

A recombinant bispecific single‐chain antibody induces targeted, supra‐agonistic CD28‐stimulation and tumor cell killing

Grosse‐Hovest, L., Hartlapp, I., Marwan, W., Brem, G., Rammensee, H., & Jung, G. (2003) · European Journal of Immunology · doi:10.1002/eji.200323322 · Cited by 62 · see citing works

Induction of Human T Lymphocyte Cytotoxicity and Inhibition of Tumor Growth by Tumor-Specific Diabody-Based Molecules Secreted from Gene-Modified Bystander Cells

Blanco, B., Holliger, P., Vile, R. G., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.2.1070 · Cited by 59 · see citing works

Alternative antibody formats.

Kontermann, R. E. (2010) · PubMed · Cited by 56 · 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

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

Phase I dose-escalation study of tumor necrosis factor-alpha and concomitant radiation therapy.

Hallahan, D. E., Vokes, E. E., Rubin, S. J., et al. (2006) · PubMed · Cited by 53 · see citing works

Development of new multivalent-bispecific agents for pretargeting tumor localization and therapy.

Rossi, E. A., Sharkey, R. M., McBride, W. J. H., et al. (2003) · PubMed · Cited by 52 · see citing works

Induction of anti-tumor immunity by trifunctional antibodies in patients with peritoneal carcinomatosis

Ströhlein, M. A., Siegel, R., Jäger, M., Lindhofer, H., Jauch, K., & Heiss, M. M. (2009) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-28-18 · Cited by 52 · see citing works

A Novel Antibody–4-1BBL Fusion Protein for Targeted Costimulation in Cancer Immunotherapy

Müller, D., Frey, K., & Kontermann, R. E. (2008) · Journal of Immunotherapy · doi:10.1097/cji.0b013e31818353e9 · Cited by 49 · see citing works

Tumor Necrosis Factor and Cancer

de Witte, M., Shealy, D. J., Nakada, M. T., & Anderson, G. M. (2007) · Humana Press eBooks · doi:10.1007/978-1-59745-455-1_4 · Cited by 45 · see citing works

Catumaxomab, a rat/murine hybrid trifunctional bispecific monoclonal antibody for the treatment of cancer.

Shen, J., & Zhu, Z. (2008) · PubMed · Cited by 42 · see citing works

Therapeutic window of an EpCAM/CD3-specific BiTE antibody in mice is determined by a subpopulation of EpCAM-expressing lymphocytes that is absent in humans

Amann, M., Friedrich, M., Lutterbuese, P., Vieser, E., Lorenczewski, G., Petersen, L., Brischwein, K., Kufer, P., Kischel, R., Baeuerle, P. A., et al. (2008) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-008-0529-y · Cited by 40 · see citing works

A bispecific single-chain antibody that mediates target cell-restricted, supra-agonistic CD28 stimulation and killing of lymphoma cells

Otz, T., Große-Hovest, L., Hofmann, M., Rammensee, H.-G., & Jung, G. (2009) · Leukemia · doi:10.1038/leu.2008.271 · Cited by 38 · see citing works

Target-dependent T-cell Activation by Coligation With a PSMA×CD3 Diabody Induces Lysis of Prostate Cancer Cells

Bühler, P., Molnár, E., Dopfer, E. P., Wolf, P., Gierschner, D., Wetterauer, U., Schamel, W. W. A., & Elsässer‐Beile, U. (2009) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181a697eb · Cited by 37 · see citing works

Isolated Limb Perfusion with TNF-α and Melphalan in Locally Advanced Soft Tissue Sarcomas of the Extremities

Grünhagen, D. J., de Wilt, J. H. W., van Geel, A. N., Verhoef, C. K., & Eggermont, A. M. M. (2009) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-540-77960-5_16 · Cited by 31 · see citing works

Radiocurability by Targeting Tumor Necrosis Factor-α Using a Bispecific Antibody in Carcinoembryonic Antigen Transgenic Mice

Larbouret, C., Robert, B., Linard, C., Navarro‐Teulon, I., Gourgou, S., Bibeau, F., Martineau, P., Santoro, L., Pouget, J., Pèlegrin, A., et al. (2007) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2007.07.2372 · Cited by 14 · see citing works

Potentiation of ionising radiation by targeting tumour necrosis factor alpha using a bispecific antibody in human pancreatic cancer

Azria, D., Larbouret, C., Garambois, V., et al. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6601362 · Cited by 14 · see citing works

Bispecific Antibodies

Müller, D., & Kontermann, R. E. (2007) · Wiley eBooks · doi:10.1002/9783527619740.ch15 · Cited by 10 · see citing works

Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development

Ovacik, M., & Lin, K. (2018) · Clinical and Translational Science · doi:10.1111/cts.12567 · Cited by 299 · see citing works

Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodiesPreprint

Inoue, T., Yamamoto, Y., Sato, K., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.26.564289 · Cited by 1 · see citing works

Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies

Spiess, C., Merchant, M. A., Huang, A. J. Y., Zheng, Z., Yang, N.-Y., Peng, J., Ellerman, D. A., Shatz-Binder, W., Reilly, D. E., Yansura, D. G., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2621 · Cited by 197 · see citing works

Cancer Immunotherapy and Application of Nanoparticles in Cancers Immunotherapy as the Delivery of Immunotherapeutic Agents and as the Immunomodulators

Debele, T. A., Yeh, C.-F., & Su, W. (2020) · Cancers · doi:10.3390/cancers12123773 · Cited by 85 · see citing works

B7-H3/CD276: An Emerging Cancer Immunotherapy

Zhou, W.-T., & Jin, W. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.701006 · Cited by 295 · see citing works

Supplementary Methods from Safety and Immunogenicity of LY3415244, a Bispecific Antibody Against TIM-3 and PD-L1, in Patients With Advanced Solid Tumors

Hellmann, M. D., Bivi, N., Calderón, B., et al. (2023) · doi:10.1158/1078-0432.22478742.v1