Bispecific Antibody Development in 2022: Benefits, Challenges and Future Directions

Immunotherapies encourage the immune system to fight cancer cells, which has resulted in accelerated expansion of therapeutic antibody medicines in recent years. By February 2022, the FDA approved 109 therapeutic antibody medicines for new treatments or indications. In addition, about 300 therapeutic antibody medicines are now being tested in clinical studies.

Bispecific antibodies are a new type of immunotherapy that combines two antigen-recognizing components into a single construct that can attach to two different targets at the same time.

They can be used to recruit immune effector cells to destroy tumor cells or to inhibit two signaling pathways or cytokines at the same time. As a result, they've sparked a lot of interest for the treatment of diseases such as blood cancers, solid tumors, diabetes, pathogenic infections such as HIV, and Alzheimer's disease. In addition, they also hold great promise in promoting targeted delivery of stem and progenitor cells to improve tissue regeneration.

The upsurge in therapeutic antibodies, along with rapid advancements in antibody engineering, has resulted in a variety of bispecific antibody formats and derived molecules that diversity in size, shape, and function.

Benefits of bispecific antibodies include:

1. By utilizing a revolutionary method of action, they provide better potency.
2. They also offer improved safety profile due to lower dosage and reduced off-target binding - as observed in combination therapy.
3. They are more cost-effective.

Bispecific antibodies have all of these advantages, making them potentially strong therapy. Despite the various benefits that bispecific forms have provided, there are two hurdles in designing them:

1. Over-engineering of naturally generated antibodies may lead to an antibody therapeutic to produce its own immune response, making the drug ineffective.
2. Commercially generating bispecific antibodies can have manufacturing problems due to their non-natural format, such as product instability, low expression level and complex purification process.

Looking ahead, a number of promising concepts in the early stages of development have emerged.

1. Some research teams have leveraged the natural structure of antibody classes with J-chains (e.g., IgM and IgA) to attach effector cell targeting arms to the J-chain so that a 1+10 bispecific antibody can be assembled, and one antibody of this kind is now in clinical phase I, demonstrating relatively good clinical results.

1. Another novel concept of bispecific antibodies is to deliver mRNA and DNA to express bispecific antibodies after transcription in vivo, both of which have shown better tumor clearance in animals. In industrial preparation, mRNA and DNA are produced faster than proteins, which will most likely accelerate the clinical development of new antibodies. In particular, DNA is not only cheaper to produce and more stable than mRNA or antibody proteins, but also offers great convenience for long-term storage and transportation. Such targeted delivery of bispecific antibodies to DNA could be used against viral and bacterial infections, and would most likely be a safe alternative to viral vaccines.
2. In addition, another new concept is to add bispecific antibodies or receptor proteins to oncolytic virus or CAR-T cell to achieve targeted delivery and function in the tumor microenvironment.

Possessing enriched experience in bispecific antibody development and a wide range of established platforms, Creative Biolabs offers innovative and sophisticated bispecific antibody development services tailored to customers’ exact needs.

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