Bispecific antibodies (bsAbs) are a significant breakthrough in cancer therapy, offering unique mechanisms of action that conventional antibodies cannot provide. As of 2023, 14 bsAbs have been approved, with 11 specifically targeting cancer. These antibodies come in various formats and target different molecules to mediate anticancer functions through diverse mechanisms.
BsAbs can function in combinatorial or obligate ways, either combining the activities of two antibodies into one molecule or requiring simultaneous binding to two targets for activity. They have been developed for various therapeutic approaches, including dual receptor inhibition, receptor activation, targeted payload delivery, and immunotherapy. The design of bsAbs takes into account factors like target choice, epitope locations, and molecular size to optimize therapeutic effects.
Over 300 clinical trials are currently investigating more than 200 bsAbs, primarily for solid tumors and hematological malignancies. The majority of these antibodies are in advanced stages of development, focusing on cancer immunotherapy, dual targeting of cancer-associated signaling pathways, and antibody-drug conjugates (ADCs).
Specific bsAb therapies include dual receptor inhibition, receptor activation, targeted payload delivery, and cancer immunotherapy. For instance, Amivantamab targets EGFR and MET for non-small cell lung cancer (NSCLC) treatment under the dual receptor inhibition approach. Agonistic antibodies targeting death receptors or co-stimulatory ligands on immune cells have shown potential under the receptor activation approach.
Emerging concepts in the field include trispecific antibodies, prodrug approaches, PROTAC bsAbs, bsAb delivery, and cytokine mimetic antibodies. These concepts aim to enhance therapeutic efficacy, selectively activate bsAbs at the tumor site, target cell surface proteins for degradation, locally produce and deliver bsAbs, and mimic cytokine action to modulate immune responses, respectively.
The field of bsAbs is rapidly evolving, with ongoing research to overcome challenges such as tumor heterogeneity and systemic toxicity. Future developments are expected to focus on enhancing the specificity and efficacy of bsAbs, integrating them with other therapeutic modalities, and exploring novel mechanisms of action for cancer treatment.
In conclusion, bsAbs represent a promising class of therapeutics in oncology, with the potential to address unmet needs in cancer treatment through their unique mechanisms of action and ability to target multiple pathways simultaneously. Continued research and clinical development will be crucial to fully realize their therapeutic potential and improve outcomes for cancer patients.
Reference:
Klein, C., Brinkmann, U., Reichert, J.M. et al. The present and future of bispecific antibodies for cancer therapy. Nat Rev Drug Discov 23, 301–319 (2024). https://doi.org/10.1038/s41573-024-00896-6 (https://www.nature.com/articles/s41573-024-00896-6)
