MULTISPECIFIC ANTIBODIES
OVERVIEW
Multispecific antibodies are engineered proteins that bind two or more different antigens or epitopes. By combining multiple specificities in a single molecule, these constructs enable new mechanisms of tumour targeting and immune engagement that ordinary monoclonal antibodies cannot provide.
Function of Multispecific Antibodies
Redirect immune effector cells (T cells, NK cells, macrophages) to tumour cells without the need for peptide presentation by major histocompatibility complex. 1
- Increase tumour selectivity via dual-antigen recognition (avidity), potentially lowering on-target/off-tumour toxicity.
- Simultaneously block multiple oncogenic pathways or combine blockade with immune recruitment. 3
Therapeutic Potential & Clinical Advantages
Overcome antigen escape and heterogeneity — targeting two or more tumour antigens reduces the chance that antigen loss variants will cause relapse.
- Synergistic mechanisms in one drug — combining targeting + immune recruitment or blockade + co-stimulation in a single molecule can increase efficacy with potentially simpler dosing. 3
Relevant Targets
- Goebeler, M.-E., et al. Bispecific and multispecific antibodies in oncology. Nat Rev Clin Oncol. 2024 Jul;21(7):539-560.
- Sun, Y, et al. Bispecific antibodies in cancer therapy: Target selection and regulatory requirements. Acta Pharm Sin B. 2023 May 23;13(9):3583–3597.
- Fine, J, et al. Mechanism-Driven Design of Multispecific Antibodies for targeted disease treatment. Annu Rev Chem Biomol Eng. 2024;Jan26:100522-102155.
- Garfall AL, et al. Trispecific antibodies offer a third way forward for anticancer immunotherapy. Nature. 2019;575(7783):450-451.
- Wang, J, et al. Design and Characterization of Bispecific and Trispecific Antibodies Targeting SARS-CoV-2. Vaccines (Basel). 2025 Feb 28;13(3):255.
