Bispecific Antibody (bsAb) Construct Formats and their Application in Cancer Therapy

Author(s): Desmond O. Acheampong*

Journal Name: Protein & Peptide Letters

Volume 26 , Issue 7 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Development of cancers mostly involves more than one signal pathways, because of the complicated nature of cancer cells. As such, the most effective treatment option is the one that stops the cancer cells in their tracks by targeting these signal pathways simultaneously. This explains why therapeutic monoclonal antibodies targeted at cancers exert utmost activity when two or more are used as combination therapy. This notwithstanding, studies elsewhere have proven that when bispecific antibody (bsAb) is engineered from two conventional monoclonal antibodies or their chains, it produces better activity than when used as combination therapy. This therefore presents bispecific antibody (bsAb) as the appropriate and best therapeutic agent for the treatment of such cancers. This review therefore discusses the various engineering formats for bispecific antibodies (bsAbs) and their applications.

Keywords: Bispecific antibodies, monoclonal antibodies, combination therapy, monotherapy, cancers/tumors, therapeutic agent.

Creixell, P.; Reimand, J.; Haider, S.; Wu, G.; Shibata, T.; Vazquez, M.; Mustonen, V.; Gonzalez-Perez, A.; Pearson, J.; Sander, C. Pathway and network analysis of cancer genomes. Nat. Methods, 2015, 12(7), 615-621. []. [PMID: 26125594].
Pitt, J.M.; Marabelle, A.; Eggermont, A.; Soria, J.C.; Kroemer, G.; Zitvogel, L. Targeting the tumor microenvironment: Removing obstruction to anticancer immune responses and immunotherapy. Ann. Oncol., 2016, 27(8), 1482-1492. []. [PMID: 27069014].
Ecker, D.M.; Jones, S.D.; Levine, H.L. The therapeutic monoclonal antibody market. MAbs, 2015, 7(1), 9-14. []. [PMID: 25529996].
Vétizou, M.; Pitt, J.M.; Daillère, R.; Lepage, P.; Waldschmitt, N.; Flament, C.; Rusakiewicz, S.; Routy, B.; Roberti, M.P.; Duong, C.P. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science, 2015, 350(6264), 1079-1084. []. [PMID: 26541610].
Postow, M.A.; Callahan, M.K.; Wolchok, J.D. Immune checkpoint blockade in cancer therapy. J. Clin. Oncol., 2015, 33(17), 1974-1982. []. [PMID: 25605845].
Weiner, G.J. Building better monoclonal antibody-based therapeutics. Nat. Rev. Cancer, 2015, 15(6), 361-370. []. [PMID: 25998715].
Xu, M.; Jin, H.; Chen, Z.; Xie, W.; Wang, Y.; Wang, Y.; Wang, M.; Zhang, J.; Acheampong, D.O. A novel bispecific diabody targeting both vascular endothelial growth factor receptor 2 and epidermal growth factor receptor for enhanced antitumor activity. Biotechnol. Prog., 2016, 32(2), 294-302. []. [PMID: 26785424].
Chen, Z.; Xie, W.; Acheampong, D.O.; Xu, M.; He, H.; Yang, M.; Li, C.; Luo, C.; Wang, M.; Zhang, J. A human IgG-like bispecific antibody co-targeting epidermal growth factor receptor and the vascular endothelial growth factor receptor 2 for enhanced antitumor activity. Cancer Biol. Ther., 2016, 17(2), 139-150. []. [PMID: 26671532].
Acheampong, D.O.; Adokoh, C.K.; Asante, D-B.; Asiamah, E.A. Acheampong, D.O.; Adokoh, C.K.; Asante, D.B.; Asiamah, E.A.; Barnie, P.A.; Bonsu, D.O; Kyei, F. Immunotherapy for acute myeloid leukemia (AML): A potent alternative therapy. Biomed. Pharmacother., 2018, 97, 225-232. []. [PMID: 29091870].
Acheampong, D.O.; Tang, M.; Wang, Y.; Zhao, X.; Xie, W.; Chen, Z.; Tian, W.; Wang, M.; Zhang, J. A novel fusion antibody exhibits antiangiogenic activity and stimulates NK cell-mediated immune surveillance through fused NKG2D ligand. J. Immunother., 2017, 40(3), 94-103. []. [PMID: 28234666].
Fan, G.; Wang, Z.; Hao, M.; Li, J. Bispecific antibodies and their applications. J. Hematol. Oncol., 2015, 8, 130. []. [PMID: 26692321].
Zhang, X.; Yang, Y.; Fan, D.; Xiong, D. The development of bispecific antibodies and their applications in tumor immune escape. Exp. Hematol. Oncol., 2017, 6, 12. []. [PMID: 28469973].
Kontermann, R.E.; Brinkmann, U. Bispecific antibodies. Drug Discov. Today, 2015, 20(7), 838-847. []. [PMID: 25728220].
Spasevska, I. An outlook on bispecific antibodies: Methods of production and therapeutic benefits; Biosci. Master Rev, 2014, pp. 1-7.
Krah, S.; Sellmann, C.; Rhiel, L.; Schröter, C.; Dickgiesser, S.; Beck, J.; Zielonka, S.; Toleikis, L.; Hock, B.; Kolmar, H.; Becker, S. Engineering bispecific antibodies with defined chain pairing. . N. Biotechnol., 2017, 39(Pt B), 167-173. [] [PMID: 28137467]
Yang, F.; Wen, W.; Qin, W. Bispecific antibodies as a development platform for new concepts and treatment strategies. Int. J. Mol. Sci., 2016, 18(1), 48. []. [PMID: 28036020].
Labrijn, A.F.; Meesters, J.I.; Bunce, M.; Armstrong, A.A.; Somani, S.; Nesspor, T.C.; Chiu, M.L.; Altintaş, I.; Verploegen, S.; Schuurman, J.; Parren, P.W.H.I. Efficient generation of bispecific murine antibodies for pre-clinical investigations in syngeneic rodent models. Sci. Rep., 2017, 7(1), 2476. []. [PMID: 28559564].
Kobayashi, T.; Takahashi, M. Tanggis; Mulyanto; Jirintai, S.; Nagashima, S.; Nishizawa, T.; Okamoto, H. Characterization and epitope mapping of monoclonal antibodies raised against rat hepatitis E virus capsid protein: An evaluation of their neutralizing activity in a cell culture system. J. Virol. Methods, 2016, 233, 78-88. []. [PMID: 26992654].
Shatz, W.; Chung, S.; Li, B.; Marshall, B.; Tejada, M.; Phung, W.; Sandoval, W.; Kelley, R.F.; Scheer, J.M. Knobs-into-holes antibody production in mammalian cell lines reveals that asymmetric afucosylation is sufficient for full antibody-dependent cellular cytotoxicity. MAbs, 2013, 5(6), 872-881. []. [PMID: 23995614].
Arathoon, W.R.; Carter, P.J.; Merchant, A.M.; Presta, L.G. Method for making multispecific antibodies having heteromultimeric and common components Google Patents, WO1998050431A3,, 2014.
Spiess, C.; Merchant, M.; Huang, A.; Zheng, Z.; Yang, N-Y.; Peng, J.; Ellerman, D.; Shatz, W.; Reilly, D.; Yansura, D.G.; Scheer, J.M. Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies. Nat. Biotechnol., 2013, 31(8), 753-758. []. [PMID: 23831709].
Schaefer, W.; Regula, J.T.; Bähner, M.; Schanzer, J.; Croasdale, R.; Dürr, H.; Gassner, C.; Georges, G.; Kettenberger, H.; Imhof-Jung, S. Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies. Proc. Natl. Acad. Sci. USA, 2011, 108(27), 11187-11192. []. [PMID: 21690412].
Vincent, K.J.; Zurini, M. Current strategies in antibody engineering: Fc engineering and pH-dependent antigen binding, bispecific antibodies and antibody drug conjugates. Biotechnol. J., 2012, 7(12), 1444-1450. []. [PMID: 23125076].
Wu, C.; Ying, H.; Grinnell, C.; Bryant, S.; Miller, R.; Clabbers, A.; Bose, S.; McCarthy, D.; Zhu, R.R.; Santora, L. Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin. Nat. Biotechnol., 2007, 25(11), 1290-1297. []. [PMID: 17934452].
Jakob, C.G.; Edalji, R.; Judge, R.A.; DiGiammarino, E.; Li, Y.; Gu, J.; Ghayur, T. Structure reveals function of the dual variable domain immunoglobulin (DVD-Ig™) molecule. MAbs, 2013, 5(3), 358-363. []. [PMID: 23549062].
Ayyar, B.V.; Arora, S.; O’Kennedy, R. Coming-of-age of antibodies in cancer therapeutics. Trends Pharmacol. Sci., 2016, 37(12), 1009-1028. []. [PMID: 27745709].
Adamson, P.; Ertl, P.F.; Germaschewski, V.; Gough, G.W.; Steward, M. Combination of a tnf-alpha antagonist and a vegf antagonist for use in the treatment or prevention of diseases of the eye. U.S. Patent 20120076787, 2010.
Eigenbrot, C.; Fuh, G. Two-in-One antibodies with dual action Fabs. Curr. Opin. Chem. Biol., 2013, 17(3), 400-405. []. [PMID: 23683347].
Jiang, G.; Lee, C.W.; Wong, P.Y.; Gazzano-Santoro, H. Evaluation of semi-homogeneous assay formats for dual-specificity antibodies. J. Immunol. Methods, 2013, 387(1-2), 51-56. []. [PMID: 23063556].
Koenig, P.; Lee, C.V.; Sanowar, S.; Wu, P.; Stinson, J.; Harris, S.F.; Fuh, G. Deep sequencing-guided design of a high affinity dual specificity antibody to target two angiogenic factors in neovascular age-related macular degeneration. J. Biol. Chem., 2015, 290(36), 21773-21786. []. [PMID: 26088137].
Yang, X.; Ambrogelly, A. Enlarging the repertoire of therapeutic monoclonal antibodies platforms: Domesticating half molecule exchange to produce stable IgG4 and IgG1 bispecific antibodies. Curr. Opin. Biotechnol., 2014, 30, 225-229. []. [PMID: 25254943].
Labrijn, A.F.; Meesters, J.I.; Priem, P.; De Jong, R.N.; Van Den Bremer, E.T.; Van Kampen, M.D.; Gerritsen, A.F.; Schuurman, J.; Parren, P.W. Controlled Fab-arm exchange for the generation of stable bispecific IgG1. Nat. Protoc., 2014, 9, 2450-2463. [].
Sedykh, S.E.; Buneva, V.N.; Nevinsky, G.A. Human milk sIgA molecules contain various combinations of different antigen-binding sites resulting in a multiple binding specificity of antibodies and enzymatic activities of abzymes. PLoS One, 2012, 7(11)e48756 []. [PMID: 23133657].
Skegro, D.; Stutz, C.; Ollier, R.; Svensson, E.; Wassmann, P.; Bourquin, F.; Monney, T.; Gn, S.; Blein, S. Immunoglobulin domain interface exchange as a platform technology for the generation of Fc heterodimers and bispecific antibodies. J. Biol. Chem., 2017, 292(23), 9745-9759. []. [PMID: 28450393].
Fischer, N.; Elson, G.; Magistrelli, G.; Dheilly, E.; Fouque, N.; Laurendon, A.; Gueneau, F.; Ravn, U.; Depoisier, J.F.; Moine, V. Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG. Nat. Commun., 2015, 6, 6113. []. [PMID: 25672245].
Nemazee, D. Mechanisms of central tolerance for B cells. Nat. Rev. Immunol., 2017, 17(5), 281. []. [PMID: 28368006].
van den Bremer, E.T.J.; Labrijn, A.F.; van den Boogaard, R.; Priem, P.; Scheffler, K.; Melis, J.P.M.; Schuurman, J.; Parren, P.W.H.I.; de Jong, R.N. Cysteine-SILAC mass spectrometry enables the identification and quantitation of scrambled inter-chain disulfide bonds: Preservation of native heavy-light chain pairing in bispecific IgGs generated by controlled Fab-arm exchange. Anal. Chem., 2017, 89(20), 10873-10882. []. [PMID: 28922593].
Blokzijl, A.; Zieba, A.; Hust, M.; Schirrmann, T.; Helmsing, S.; Grannas, K.; Hertz, E.; Moren, A.; Chen, L. Single chain antibodies as tools to study transforming growth factor-β-regulated SMAD proteins in proximity ligation-based pharmacological screens. Mol. Cell. Proteomics, 2016, 15(6), 1848-1856. []. [PMID: 26929218].
DeKosky, B.J.; Lungu, O.I.; Park, D.; Johnson, E.L.; Charab, W.; Chrysostomou, C.; Kuroda, D.; Ellington, A.D.; Ippolito, G.C.; Gray, J.J. Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires. Proc. Natl. Acad. Sci. USA, 2016, 113(19), E2636-E2645. []. [PMID: 27114511].
Du, X.J.; Zhou, X.N.; Li, P.; Sheng, W.; Ducancel, F.; Wang, S. Ducancel, Fdr.; Wang, S. Development of an immunoassay for chloramphenicol based on the preparation of a specific single-chain variable fragment antibody. J. Agric. Food Chem., 2016, 64(14), 2971-2979. []. [PMID: 27003441].
Kovář, D. Immunospecific sensors based on nanoparticles and nanostructures.Masarykova Univerzita Přírodovědecká Fakulta. PhD Thesis, Masaryk University, Faculty of Science: Brno. 2015.
Hollander, N. Bispecific antibodies for cancer therapy. Immunotherapy, 2009, 1(2), 211-222. [].
Gallo, E.; Snyder, A.C.; Jarvik, J.W. Engineering tandem single-chain Fv as cell surface reporters with enhanced properties of fluorescence detection. Protein Eng. Des. Sel., 2015, 28(10), 327-337. []. [PMID: 25843939].
Grandjenette, C.; Dicato, M.; Diederich, M. Bispecific antibodies: An innovative arsenal to hunt, grab and destroy cancer cells. Curr. Pharm. Biotechnol., 2015, 16(8), 670-683. []. [PMID: 25941884].
Hazlett, K.; Gosselin, E.; Sellati, T.; Zarrella, T. Fusion protein for enhancing immunogenicity of bacterial antigen/immunogen. Google Patents; WO2013110064A1 2016.
Compte, M.; Álvarez-Cienfuegos, A.; Nuñez-Prado, N.; Sainz-Pastor, N.; Blanco-Toribio, A.; Pescador, N.; Sanz, L.; Álvarez-Vallina, L. Functional comparison of single-chain and two-chain anti-CD3-based bispecific antibodies in gene immunotherapy applications. OncoImmunology, 2014, 3e, 28810. []. [PMID: 25057445].
Shan, G-Y.; Zhang, J-H.; Fan, Q-X. Analysis of the relationship between molecular conformation of single-chain variable fragment and in vitro biological activities by modeling. J. Comput. Theor. Nanosci., 2014, 11, 1100-1106. [].
Smits, N.C.; Sentman, C.L. Bispecific T-cell engagers (BiTEs) as treatment of B-cell lymphoma. J. Clin. Oncol., 2016, 34(10), 1131-1133. []. [PMID: 26884583].
Ng, G.Y.K.; Dixit, S.B.; Kreudenstein, V.; Bispecific, T.S. CD3 and CD19 antigen binding constructs. . Canada Patents; CA2917886A1, 2014.
Asano, R.; Ikoma, K.; Shimomura, I.; Taki, S.; Nakanishi, T.; Umetsu, M.; Kumagai, I. Cytotoxic enhancement of a bispecific diabody by format conversion to tandem single-chain variable fragment (taFv): The case of the hEx3 diabody. J. Biol. Chem., 2011, 286(3), 1812-1818. []. [PMID: 21097496].
Brinkmann, U.; Kontermann, R.E. The making of bispecific antibodies. MAbs, 2017, 9(2), 182-212. []. [PMID: 28071970].
Bahmani, P.; Hosseinkhani, S. Increase of segmental mobility through insertion of a flexible linker in split point of firefly luciferase. Int. J. Biol. Macromol., , 2017, 94(Pt B), 762-770. [] [PMID: 27026341]
Rabenhold, M.; Steiniger, F.; Fahr, A.; Kontermann, R.E.; Rüger, R. Bispecific single-chain diabody-immunoliposomes targeting endoglin (CD105) and fibroblast activation protein (FAP) simultaneously. J. Control. Release, 2015, 201, 56-67. []. [PMID: 25617725].
Reusch, U.; Harrington, K.H.; Gudgeon, C.J.; Fucek, I.; Ellwanger, K.; Weichel, M.; Knackmuss, S.H.; Zhukovsky, E.A.; Fox, J.A.; Kunkel, L.A. Characterization of CD33/CD3 tetravalent bispecific tandem diabodies (TandAbs) for the treatment of acute myeloid leukemia. Clin. Cancer Res., 2016, 22(23), 5829-5838. []. [PMID: 27189165].
Brien, J.D.; Sukupolvi-Petty, S.; Williams, K.L.; Lam, C.Y.; Schmid, M.A.; Johnson, S.; Harris, E.; Diamond, M.S. Protection by immunoglobulin dual-affinity retargeting antibodies against dengue virus. J. Virol., 2013, 87(13), 7747-7753. []. [PMID: 23658441].
Muyldermans, S. Nanobodies: natural single-domain antibodies. Annu. Rev. Biochem., 2013, 82, 775-797. []. [PMID: 23495938].
Wozniak-Knopp, G.; Stadlmayr, G.; Perthold, J.W.; Stadlbauer, K.; Woisetschläger, M.; Sun, H.; Rüker, F. Designing Fcabs: Well-expressed and stable high affinity antigen-binding Fc fragments. Protein Eng. Des. Sel., 2017, 30(9), 1-15. []. [PMID: 28981753].
Knopp, G.W.; Stadlmayr, G.; Ruker, F. IgG Fc fragment as a scaffold for development of targeted therapeutics. Curr. Pharm. Biotechnol., 2016, 17(15), 1315-1323. []. [PMID: 27842481].
McBride, W.J.; Goldenberg, D.M. Methods and compositions for F-18 labeling of proteins, peptides and molecules U.S. Patent US8147800B2, 2013.
Rogers, B.; Dong, D.; Li, Z.; Li, Z. Recombinant human serum albumin fusion proteins and novel applications in drug delivery and therapy. Curr. Pharm. Des., 2015, 21(14), 1899-1907. []. [PMID: 25732550].
Wu, M.R. Harnessing natural killer cell receptors for tumor immunotherapy.. PhD Thesis, Dartmouth College: Hanover, New Hampshire, January . 2015. []
Brennan, T.; Dean, R.; Kavanaugh, W.M. Powers J: Hair growth methods using fgfr3 extracellular domains. Google Patents; WO2011084711A2, 2014.
Ginn, C.; Khalili, H.; Lever, R.; Brocchini, S. PEGylation and its impact on the design of new protein-based medicines. Future Med. Chem., 2014, 6(16), 1829-1846. []. [PMID: 25407370].
Tung, C.L.; Wong, C.T.; Fung, E.Y.M.; Li, X. Traceless and chemoselective amine bioconjugation via phthalimidine formation in native protein modification. Org. Lett., 2016, 18(11), 2600-2603. []. [PMID: 27191384].
Liu, S.; Jiang, S. Zwitterionic polymer-protein conjugates reduce polymer-specific antibody response. Nano Today, 2016, 11, 285-291. [].
Carmali, S.; Murata, H.; Amemiya, E.; Matyjaszewski, K.; Russell, A.J. Tertiary structure-based prediction of how ATRP initiators react with proteins. ACS Biomater. Sci. Eng., 2017, 3(9), 2086-2097. [].
Stefan, N.; Zimmermann, M.; Simon, M.; Zangemeister-Wittke, U.; Plückthun, A. Novel prodrug-like fusion toxin with protease-sensitive bioorthogonal PEGylation for tumor targeting. Bioconjug. Chem., 2014, 25(12), 2144-2156. []. [PMID: 25350699].
Goswami, S.; Wang, W.; Arakawa, T.; Ohtake, S. Developments and challenges for mAb-based therapeutics. Antibodies (Basel), 2013, 2, 452-500. [].
Zhao, L.; Alemu, L.; Cheng, J.; Zhen, T.; Friedman, A.D.; Liu, P.P. The multimerization domain of Cbfß-SMMHC is required for leukemogenesis. Blood, 2015, 126, 3666.
Raulet, D.H.; Marcus, A.; Coscoy, L. Dysregulated cellular functions and cell stress pathways provide critical cues for activating and targeting natural killer cells to transformed and infected cells. Immunol. Rev., 2017, 280(1), 93-101. []. [PMID: 29027233].
Park, J.A.; Cheung, N-K.V. Limitations and opportunities for immune checkpoint inhibitors in pediatric malignancies. Cancer Treat. Rev., 2017. [].
Conlon, K.C.; Lugli, E.; Welles, H.C.; Rosenberg, S.A.; Fojo, A.T.; Morris, J.C.; Fleisher, T.A.; Dubois, S.P.; Perera, L.P.; Stewart, D.M.; Goldman, C.K.; Bryant, B.R.; Decker, J.M.; Chen, J.; Worthy, T.A.; Figg, W.D., Sr; Peer, C.J.; Sneller, M.C.; Lane, H.C.; Yovandich, J.L.; Creekmore, S.P.; Roederer, M.; Waldmann, T.A. Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. J. Clin. Oncol., 2015, 33(1), 74-82. []. [PMID: 25403209].
Eissler, N.; Mysliwietz, J.; Deppisch, N.; Ruf, P.; Lindhofer, H.; Mocikat, R. Potential of the trifunctional bispecific antibody surek depends on dendritic cells: Rationale for a new approach of tumor immunotherapy. Mol. Med., 2013, 19, 54-61. []. [PMID: 23552725].
De Simone, V.; Franzè, E.; Ronchetti, G.; Colantoni, A.; Fantini, M.C.; Di Fusco, D.; Sica, G.S.; Sileri, P.; MacDonald, T.T.; Pallone, F.; Monteleone, G.; Stolfi, C. Th17-type cytokines, IL-6 and TNF-α synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth. Oncogene, 2015, 34(27), 3493-3503. []. [PMID: 25174402].
Lameris, R.; de Bruin, R.C.; Schneiders, F.L. van Bergen en Henegouwen, P.M.; Verheul, H.M.; de Gruijl, T.D.; van der Vliet, H.J. Bispecific antibody platforms for cancer immunotherapy. Crit. Rev. Oncol. Hematol., 2014, 92(3), 153-165. []. [PMID: 25195094].
Tang, F.; Xu, L.; Yan, R.; Song, X.; Li, X. A DNA vaccine co-expressing Trichinella spiralis MIF and MCD-1 with murine ubiquitin induces partial protective immunity in mice. J. Helminthol., 2013, 87(1), 24-33. []. [PMID: 22221593].
Lindhofer, H.; Buhmann, R.; Dreyling, M.; Hiddemann, W. Subcutaneously administered bispecific antibodies for use in the treatment of cancer. Google Patents; W02016020065A1, , 2015.
Huehls, A.M.; Coupet, T.A.; Sentman, C.L. Bispecific T-cell engagers for cancer immunotherapy. Immunol. Cell Biol., 2015, 93(3), 290-296. []. [PMID: 25367186].
Topp, M.S.; Gökbuget, N.; Zugmaier, G.; Klappers, P.; Stelljes, M.; Neumann, S.; Viardot, A.; Marks, R.; Diedrich, H.; Faul, C.; Reichle, A.; Horst, H.A.; Brüggemann, M.; Wessiepe, D.; Holland, C.; Alekar, S.; Mergen, N.; Einsele, H.; Hoelzer, D.; Bargou, R.C. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J. Clin. Oncol., 2014, 32(36), 4134-4140. []. [PMID: 25385737].
Zimmerman, Z.; Maniar, T.; Nagorsen, D. Unleashing the clinical power of T cells: CD19/CD3 bi-specific T cell engager (BiTE®) antibody construct blinatumomab as a potential therapy. Int. Immunol., 2015, 27(1), 31-37. []. [PMID: 25239133].
Sallman, D.A.; Davila, M.L. Is disease-specific immunotherapy a potential reality for MDS? Clin. Lymphoma Myeloma Leuk., 2017, 17S, S26-S30. []. [PMID: 28760299].
de la Roche, M.; Asano, Y.; Griffiths, G.M. Origins of the cytolytic synapse. Nat. Rev. Immunol., 2016, 16(7), 421-432. []. [PMID: 27265595].
Vazquez, M.I.; Catalan-Dibene, J.; Zlotnik, A. B cells responses and cytokine production are regulated by their immune microenvironment. Cytokine, 2015, 74(2), 318-326. []. [PMID: 25742773].
Yuraszeck, T.; Kasichayanula, S.; Benjamin, J.E. Translation and clinical development of bispecific T-cell engaging antibodies for cancer treatment. Clin. Pharmacol. Ther., 2017, 101(5), 634-645. []. [PMID: 28182247].
Sloan, D.D.; Lam, C.Y.; Irrinki, A.; Liu, L.; Tsai, A.; Pace, C.S.; Kaur, J.; Murry, J.P.; Balakrishnan, M.; Moore, P.A. Targeting HIV reservoir in infected CD4 T cells by dual-affinity re-targeting molecules (DARTs) that bind HIV envelope and recruit cytotoxic T cells. PLoS Pathog., 2015, 11(11)e1005233 []. [PMID: 26539983].
Spiess, C.; Zhai, Q.; Carter, P.J. Alternative molecular formats and therapeutic applications for bispecific antibodies. Mol. Immunol., 2015, 67(2 Pt A), 95-106. []. [PMID: 25637431].
Chichili, G.R.; Huang, L.; Li, H.; Burke, S.; He, L.; Tang, Q.; Jin, L.; Gorlatov, S.; Ciccarone, V.; Chen, F.A. CD3xCD123 bispecific DART for redirecting host T cells to myelogenous leukemia: preclinical activity and safety in nonhuman primates. Science translational medicine, 2015. [].
Reusch, U.; Burkhardt, C.; Fucek, I.; Le Gall, F.; Le Gall, M.; Hoffmann, K.; Knackmuss, S.H.; Kiprijanov, S.; Little, M.; Zhukovsky, E.A. A novel tetravalent bispecific TandAb (CD30/CD16A) efficiently recruits NK cells for the lysis of CD30+ tumor cells. MAbs, 2014, 6(3), 728-739.
Vyas, M.; Koehl, U.; Hallek, M.; von Strandmann, E.P. Natural ligands and antibody-based fusion proteins: Harnessing the immune system against cancer. Trends Mol. Med., 2014, 20(2), 72-82. []. [PMID: 24268686].
Rothe, A.; Sasse, S.; Topp, M.S.; Eichenauer, D.A.; Hummel, H.; Reiners, K.S.; Dietlein, M.; Kuhnert, G.; Kessler, J.; Buerkle, C. A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. Blood, 2015, 125(26), 4024-4031. []. [PMID: 25887777].
Shiota, M.; Bishop, J.L.; Takeuchi, A.; Nip, K.M.; Cordonnier, T.; Beraldi, E.; Kuruma, H.; Gleave, M.E.; Zoubeidi, A. Inhibition of the HER2-YB1-AR axis with Lapatinib synergistically enhances Enzalutamide anti-tumor efficacy in castration resistant prostate cancer. Oncotarget, 2015, 6(11), 9086-9098. []. [PMID: 25871401].
Huang, Y.; Fu, P.; Fan, W. Novel targeted therapies to overcome trastuzumab resistance in HER2-overexpressing metastatic breast cancer. Curr. Drug Targets, 2013, 14(8), 889-898. []. [PMID: 23531110].
Wainszelbaum, M. J.; Fessler, J.; Lahdenranta, J.; Burenkova, O.; Gerami-Moayed, N.; Hashambhoy-Ramsay, Y.; Rimkunas, V.; MacBeath, G. Abstract LB-C25: Inhibition of ERBB3 with MM- 121, IGF1-R with MM-141 or Met with MM-131 increases the activity of EGFR inhibitor MM-151 in colorectal cancer models expressing multiple resistance ligands. AACR; Mol. Cancer Ther., 2015, 14(12), LB-C25.
Fitzgerald, J.B.; Johnson, B.W.; Baum, J.; Adams, S.; Iadevaia, S.; Tang, J.; Rimkunas, V.; Xu, L.; Kohli, N.; Rennard, R. MM-141, an IGF-IR- and ErbB3-directed bispecific antibody, overcomes network adaptations that limit activity of IGF-IR inhibitors. Mol. Cancer Ther., 2014, 13(2), 410-425. []. [PMID: 24282274].
Tumur, Z.; Guerra, C.; Yanni, P.; Eltejaye, A.; Waer, C.; Alkam, T.; Henson, B.S. Rosmarinic acid inhibits cell growth and migration in head and neck squamous cell carcinoma cell lines by attenuating epidermal growth factor receptor signaling. J. Cancer Sci. Ther., 2015, 7, 359-366. [].
Lieu, C.H.; Hidalgo, M.; Berlin, J.D.; Ko, A.H.; Cervantes, A.; LoRusso, P.; Gerber, D.E.; Eder, J.P.; Eckhardt, S.G.; Kapp, A.V.; Tsuhako, A.; McCall, B.; Pirzkall, A.; Uyei, A.; Tabernero, J. A phase Ib dose‐escalation study of the safety, tolerability,and pharmacokinetics of cobimetinib and duligotuzumab in patients with previously treated locally advanced or metastatic cancers with mutant KRAS. Oncologist, 2017, 22(9), 1024-e89. []. [PMID: 28592615].
Misale, S.; Arena, S.; Lamba, S.; Siravegna, G.; Lallo, A.; Hobor, S.; Russo, M.; Buscarino, M.; Lazzari, L.; Sartore-Bianchi, A. Blockade of EGFR and MEK intercepts heterogeneous mechanisms of acquired resistance to anti-EGFR therapies in colorectal cancer. Sci. Transl. Med., 2014, 6(224)224ra226 [].
De Pauw, I.; Wouters, A.; Van den Bossche, J.; Deschoolmeester, V.; Baysal, H.; Pauwels, P.; Peeters, M.; Vermorken, J.B.; Lardon, F. Dual targeting of epidermal growth factor receptor and HER3 by MEHD7945A as monotherapy or in combination with cisplatin partially overcomes cetuximab resistance in head and neck squamous cell carcinoma cell lines. Cancer Biother. Radiopharm., 2017, 32(7), 229-238. []. [PMID: 28910149].
Jimeno, A.; Machiels, J.P.; Wirth, L.; Specenier, P.; Seiwert, T.Y.; Mardjuadi, F.; Wang, X.; Kapp, A.V.; Royer-Joo, S.; Penuel, E. Phase Ib study of duligotuzumab (MEHD7945A) plus cisplatin/5-fluorouracil or carboplatin/paclitaxel for first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck. Cancer, 2016, 122(24), 3803-3811. []. [PMID: 27525588].
Boroughs, L.K.; DeBerardinis, R.J. Metabolic pathways promoting cancer cell survival and growth. Nat. Cell Biol., 2015, 17(4), 351-359. []. [PMID: 25774832].
Dvorak, H.F. Tumor stroma, tumor blood vessels, and antiangiogenesis therapy. Cancer J., 2015, 21(4), 237-243. []. [PMID: 26222073].
Acheampong, D.; Zhang, J.; Wang, M. Angiogenesis and cancer therapy. Int. J. Pharm. Sci. Res., 2013, 4, 2021.
Hidalgo, M.; Le Tourneau, C.; Massard, C.; Boni, V.; Calvo, E.; Albanell, J.; Taus, A.; Sablin, M-P.; Varga, A.; Bahleda, R. Results from the first-in-human (FIH) phase I study of RO5520985 (RG7221), a novel bispecific human anti-ANG-2/anti-VEGF-A antibody, administered as an intravenous infusion to patients with advanced solid tumors. J. Clin. Oncol., 2014, 32(Suppl. 15), 2525-2525. [].
Tekewe, A.; Saleh, M.; Kassaye, M. Proteins and peptides as targeting carriers in anticancer drug delivery: A review. Int. J. Pharm. Sci. Res., 2013, 4, 1.
Kibria, G.; Hatakeyama, H.; Harashima, H. Cancer multidrug resistance: Mechanisms involved and strategies for circumvention using a drug delivery system. Arch. Pharm. Res., 2014, 37(1), 4-15. []. [PMID: 24272889].
Boerman, O.C.; Heskamp, S.; Chang, C-H.; McBride, W.J.; Goldenberg, D.M. . Tumor therapy by bispecific antibody pretargeting. US Patent US20160287732A1, 2015.
Acheampong, D.O.; Adokoh, C.K.; Ampomah, P.; Agyirifor, D.S.; Dadzie, I.; Ackah, F.A.; Asiamah, E.A. Bispecific Antibodies (bsAbs): Promising immunotherapeutic agents for cancer therapy. Protein Pept. Lett., 2017, 24(5), 456-465. []. [PMID: 28117014].

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [479 - 493]
Pages: 15
DOI: 10.2174/0929866526666190311163820
Price: $65

Article Metrics

PDF: 52
HTML: 11
PRC: 2