Advances in disease biology have led to the burgeoning development of bispecific antibodies (BsAbs), which are synthetic proteins capable of targeting two discrete epitopes from different antigens. Their bispecific functionality offers promising therapeutic potential such that their applicability to a variety of therapies is being explored. Originally developed for the treatment of cancer, BsAbs may now benefit imaging and diagnostics, as well as disease prevention and treatment. Several bispecific antibodies have already obtained regulatory approval, while hundreds more are in development.

In this white paper, we will discuss the predominant formats and mechanisms of action of bispecific antibodies, the most common techniques for BsAbs transient production, and what is involved in their process development. We will also highlight the advantages of partnering with a CDMO with world-class service offerings, from discovery to production, and how doing so can ensure success of your BsAbs by delivering precise immunotherapy solutions and avoiding costly regulatory mistakes.

 

Bispecific antibodies for immunotherapy

Bispecific antibodies show incredible promise for immunotherapy as they bind to two different antigens, thereby enhancing therapeutic efficacy. This dual functionality can be tailored for precise immunogenic targeting, making BsAbs a powerful budding alternative to conventional therapies. Unfortunately, the synthesis of these bispecific molecules is complicated by the multitude of product-related impurities, such as miss paired species. Strategies for inhibiting their formation and promoting selective pairing have been developed. However, even with the optimal design, some level of undesired product-related variants is nonetheless observed.

Therefore, purification processes must include steps to remove these particular contaminants. Generally, the best outcomes stem from the combination of optimized production and the downstream processes to remove the impurities. Analytical monitoring throughout the process and downstream testing of the product are essential for ensuring the quality of the novel antibody. Development of testing is complicated by the complexity of the bispecific molecule and must be deliberated to verify that the tests fulfill the needs of the program and meet FDA guidelines.