Antibodies, a major component of adaptive immunity, play a critical role in protective and pathogenic immune responses. In recent years, a wide range of antibodies is discovered as candidates of cancer therapeutic agents, including the reconstructive molecules, bispecific antibodies (BsAbs).
About Bispecific Antibody
Bispecific antibodies, as its name indicates, consists of two antigen-binding sites, which can simultaneously bind two separate and unique antigens (or different epitopes of the same antigen). This structure is typically designed to bind to two targets, one on a cancer cell and one on an immune cell, activating or redirecting immune effector cells with the goal of getting the immune cell to kill the cancer cell by antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC) and other cytotoxic mechanisms.
Unique biological and pharmacological properties, as well as availability in different formats, broaden bispecific antibody applications and make it a novel and promising antibody therapeutic agent in the field of genetic disorders, hematological malignancies, autoimmune disorders, inflammatory disorders, eye disorders, skin disorders, etc.
Existing Market of Bispecific Antibodies Therapeutics
Inspired by the approval of two bispecific antibodies, namely Blincyto® (2014) and Hemlibra® (2017) for therapeutic use, a number of bispecific antibody companies and technology providers have devoted themselves to advancing the development of pipeline drug candidates. As a consequence, near 50 new formats of BsAbs are produced in recent years relying on advanced antibody engineering techniques. For instance, bispecific fusion protein, a major format of bispecific antibodies, could be generated by linking other proteins to the antibody or antibody fragments to add more functionality or specificity.
Clinical trials based on bispecific antibodies also contribute to the increasing popularity and therapeutic potentials. It's reported that an increase from 51 in 2014 to over 300 in 2019 was observed in the cumulative number of bispecific antibodies related studies, and over 300 bispecific drug candidates are currently in clinical or preclinical stages.
Challenges
However, building a safe and effective bispecific antibody candidate is more than challenging. The reconstructed antibody therapeutics are anticipated to activate immune cells while too many immune cells could cause cytokine release syndrome or other side effects. Specific challenges of developing bispecific antibody therapeutics could arise at various stages. But the main restraint in the development of bispecific antibodies falls on manufacturing problems, such as low expression yields, product instability, and immunogenicity. As a result, technologies that meet the growing development demand for new bispecific antibody therapeutics with better predictive screening capabilities and higher throughputs are required.
To specifically evaluate the structure, function, and quality of the bispecific antibody products in the early process, researchers have to utilize sophisticated and time-consuming analytical techniques, such as enzyme-linked immunosorbent assay (ELISA) and liquid chromatography–mass spectrometry. However, the highly competitive and economically driven bispecific antibody therapeutic market emphasizes a challenge in balancing speedy delivery without compromising quality.
Moreover, the stricter selection criteria for bsAbs than those for monospecific antibodies bring more challenges in screening and antibody characterization to identify cell lines with the highest quality and productivity. The next-generation platform for bispecific antibody sequencing like database-assisted shotgun sequencing (DASS) technology could be helpful for the sequencing of unknown BsAb antibodies, especially if there is no record of amino acid sequences of a specific antibody in the database.
The outlook of Bispecific Antibody Therapeutics Market
Reports from several market research companies have concluded that the healthcare landscape all over the world is more inclined towards using antibodies for the treatment of cancer, in which the global bispecific antibody market has surged in the past few years because its feature of targeting two different epitopes simultaneously has increased the overall therapeutic success rate.
Encouraged by factors like increasing prevalence of cancer cases, increased failure rate of other cancer therapies, and rising geriatric population, the bispecific antibody therapeutic market, not only opportunities in cancer treatment, is pegged to value $12 billion by 2026.
BsAbs is emerging as the next novel wave of biologics!
