Written by:
Senior Vice President, Biologics Engineering and Oncology Targeted Discovery, AstraZeneca
Executive Director, Biologics Engineering,
AstraZeneca
Multispecific antibodies are emerging as a leading class of biological therapeutics, with AstraZeneca at the forefront of protein engineering to deliver next generation targeted therapeutics across disease areas.
Engineering multispecific antibodies
Multispecific antibodies have the capacity to simultaneously bind to two or more target antigens on the same cell or bridge two different cells, and they complement conventional, ‘monospecific’ medicines which recognise a single target antigen.1
At AstraZeneca, we have established a multispecific discovery platform which can be customised with specific properties and mechanisms of action to selectively target complex disease biology.
How we are advancing multispecific medicines in oncology
While combination regimens are already central to our Oncology R&D strategy, advances in engineering multispecific antibodies with multiple antitumor mechanisms hold promise to unlock novel biological activity.
Cancer cells typically develop resistance to treatment by downregulating the protein target on their surface.1 By binding to more than one target, multispecific antibodies could overcome this.1 They may also improve targeted drug delivery and spare normal tissue, and modulate immune cells to specifically eliminate tumour cells.1
We have several bispecific and trispecific cancer therapies in the clinic, including:
- Antibody–drug conjugates, which bind to a target protein to deliver a cytotoxic chemotherapy agent directly to cancer cells
- Immuno-oncology agents, which simultaneously target different immune checkpoints to harness the immune system and induce an immune response against cancer
- Immune cell engagers, which are engineered to activate the immune system’s T cells and redirect them to recognise and kill cancer cells
Our vision is to redefine current chemotherapy regimens by establishing a multispecific backbone for novel cancer therapies. To achieve this, we’re advancing multispecifics drug discovery and engineering antibodies which can attack cancer from multiple angles, alone and in combinations, with the hope that we will elicit deeper, more durable responses to treatment.
Because our clinically validated multispecific drug discovery platform resembles the native IgG antibody found in the human body, it is also less likely to elicit an unwanted immune reaction when administered.
Multispecific innovation across other disease areas
Our proprietary multispecific molecules also have potential in other human diseases such as infectious diseases, chronic inflammatory diseases, cardiovascular diseases and beyond.
For example, they can simultaneously target and neutralise specific pro-inflammatory cytokines or eliminate pathogenic immune cells, and thereby reduce inflammation and autoimmunity in conditions such as rheumatoid arthritis and lupus.
To prevent infectious diseases, multispecific drugs’ ability to bind to two or more target antigens on an invading pathogen hold promise in developing immunisations which continue to promote immunity even when viruses mutate, which could lead to reduced vaccine efficacy.
We are also exploring the use of multispecifics in cardiovascular disease through simultaneous targeting of disease mediators involved in cardiovascular conditions, such as atherosclerotic plaques.
Multispecific antibodies offer a versatile platform for targeting multiple disease pathways simultaneously, holding promise for a broad range of therapeutic applications beyond oncology, to treat different human diseases.
Continuing drug discovery and development: future treatment pathways
We are moving from an era of ‘monospecific’ medicines derived from monoclonal antibodies, to a new paradigm where we can engineer therapeutic antibodies which target multiple aspects of complex disease simultaneously.
This is enabling us to access new and challenging disease targets and develop transformative multispecific molecules which have the potential to accelerate drug development from discovery into the clinic to bring targeted therapy to patients across disease areas.
