Bispecific antibodies: the next generation of immuno-oncology drugs
Taylor B Guo, Chief Scientific Officer at I-Mab, describes the potential benefits of bispecific antibodies for cancer therapy and how their dual targeting mechanisms of action may drive their emergence as the next generation of immuno-oncology drugs.
WHILE THE human body can use the immune system to fight cancer cells, many cancers are able to evade detection and escape destruction from immune cells. Immuno-oncology drugs, comprised mainly of monoclonal antibodies (mAbs), have revolutionised the treatment of cancer. Checkpoint inhibitors, like antibodies against programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1), are now first-line therapies for many oncologic indications in numerous countries. However, the therapeutic effectiveness of PD-1/PD-L1 blockade is limited to only a proportion of patients with cancer, with more than 60 percent of patients typically not responding optimally.1,2 This occurs either as a poor response from the start of treatment or arises over time due to the development of resistance to the therapy.3,4
To address this unmet need of suboptimal responder patients for other options and generally expand our armamentarium in the fight against cancer, we are working to develop the next generation of antibody oncology drugs. A prime example of such an endeavour is the creation of a new kind of antibody – one that binds specifically to not only one but two target proteins. An example of these so-called bispecific antibodies is TJ-CD4B/ ABL111 currently being co-developed with ABL Bio, which can bind with high affinity and specificity to both Claudin 18.2 (CLDN18.2) and 4-1BB.5