Bispecific Antibodies for Cancer Immunotherapy
- 882 Downloads
The concept of using bispecific antibodies to retarget immune effector cells for cancer therapy was conceived more than 20 years ago. However, initial clinical studies were rather disappointing mainly due to low efficacy, severe adverse effects and immunogenicity of the bispecific antibodies. A deeper understanding of effector cell biology and especially developments in the field of antibody engineering has led to the generation of new classes of bispecific antibodies capable of circumventing many of these obstacles. Furthermore, new applications were established for bispecific antibodies, such as pre-targeting strategies in radioimmunotherapy or dual targeting approaches in order to improve binding, selectivity, and efficacy. This review summarizes recent progress in the development of bispecific antibodies and describes some new concepts developed for cancer immunotherapy.
KeywordsBispecific Antibody Variable Heavy Hyperthermic Isolate Limb Perfusion Trifunctional Antibody Trigger Molecule
This work was supported by grants from the Deutsche Forschungsgemeinschaft (KO 1461/4, MU 2956/2-1) and the Deutsche Krebshilfe (MU 2956/2-1). The authors have no conflicts of interest that are directly relevant to the content of this review.
- 3.Chames P, Baty D. Bispecific antibodies for cancer therapy. Curr Opin Drug Discov Develop 2009; 12: 276–83Google Scholar
- 5.Kontermann RE. Alternative antibody formats. Curr Opin Mol Ther. In pressGoogle Scholar
- 23.Dreier T, Baeuerle PA, Fichtner I, et al. 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. J Immunol 2003; 170: 4397–402PubMedGoogle Scholar
- 42.Chatal JF, Campion L, Kraeber-Bodéré F, et al. Survival improvement in patients with medullary thyroid carcinoma who undergo pretargeted anti-carcinoembryonic antigen radioimmunotherapy: a collaborative study with the French Endocrine Tumor Group. J Clin Oncol 2006; 24: 1705–11PubMedCrossRefGoogle Scholar
- 55.Stork R, Müller D, Kontermann RE. A novel trifunctional antibody fusion protein with improved pharmacokientic properties generated by fusing a bispecific single-chain diabody with an albumin-binding domain form streptococcal protein G. Protein Eng Des Sel 2007; 20: 569–76PubMedCrossRefGoogle Scholar