Bispecific Antibodies for the Treatment of Cancer

Abstract

Cancer is a devastating disease that can be challenging to treat. Fortunately, immune cells called T-cells can be activated for tumour destruction. Signal 1 of T-cell activation is provided by antigen presentation through the (T-cell receptor/major histocompatibility complex) interaction. Signal 2 of T-cell activation is provided by a costimulatory interaction (CD28/CD80). Immune checkpoint blockade (programmed cell death-1/programmed cell death ligand-1 [PD-L1]) is a regulatory interaction controlling T-cell activation/repression. However, tumour cells may exploit checkpoint blockade for tumour survival. Immunotherapy is a favourable cancer therapy provided by 'the magic bullet' approach. Monoclonal antibodies provide cytostatic effects against checkpoint blockade. However, tumours may evolve modifications, including tumour antigen loss and tumour ligand overexpression (PD-L1). This can inactivate T-cells, causing immunotherapy resistance and low clinical responses. Bispecific antibodies possess superior properties to monoclonal antibodies provided by their spatio-temporal effects, with potential to improve anti-tumour activity. Bispecific antibodies in development were reviewed for their structures, development technologies and anti-tumour activities. FS118 and M7824 are used to treat refractory cancers, whilst Tebotelimab and XmAb20717 solely enhance T-cell activation for tumour destruction. As cellular factors can switch off T-cell activity leading to immunotherapy resistance, bispecifics with focus on T-cell activity may be ineffective in tumour targeting. This may provide an opportunity to develop a bispecific antibody as part of future research, with binding targets, PD-L1 and lymphocyte-activation gene 3. This may promote cytostatic effects for T-cell activation. Furthermore, effector cell binding may use antibody-dependent cellular cytotoxicity effects to ensure tumour destruction.