2021 DIA Annual Meeting | Controversy between monoclonal antibodies and double antibodies-can double antibodies replace monoclonal antibodies?

In recent years, as the pharmaceutical industry continues to deepen the research on the structure and biosynthesis technology of dual-antibody drugs, the global dual-antibody drug market has ushered in an explosive period.

According to Yang Nong, assistant to the dean of Hunan Cancer Hospital, director of the Department of Medical Oncology, and director of the Department of Pulmonary and Gastrointestinal Oncology, the concept of dual antibodies emerged in 1960.

(1) The difference between monoclonal antibodies and double antibodies

Bispecific Antibody (bsAb, Bispecific Antibody) is a new type of second-generation antibody that has two specific antigen binding sites and can interact with target cells and functional cells at the same time, thereby enhancing the killing of target cells.

Compared with monoclonal antibodies, double antibodies add a specific antigen binding site, so they have stronger specificity, more accurately target tumor cells and reduce off-target toxicity.

(1) The two antigen binding sites can bind to tumor cells and immune cells, redirect immune cells, recruit immune cells around the tumor cells, and enhance the lethality of the tumor;

(2) Two different signal pathways can be blocked at the same time to enhance cell killing toxicity;

(3) After binding to two different cell surface antigens, relatively speaking, it may potentially increase the binding specificity and reduce the side effects caused by off-target.

Figure 1: The difference between a monoclonal antibody and a double antibody (BiTE)

(2) Combination therapy of double antibodies and monoclonal antibodies

In addition to its superior efficacy over monoclonal antibodies, double antibodies are expected to reduce the incidence of high adverse events in combination therapy.

However, the combination therapy has always been accompanied by a significant increase in dose-limiting treatment-related toxicity (TRAE) while increasing its anti-tumor activity, resulting in unsatisfactory safety.

The double antibody is expected to retain the efficacy of the combination therapy and establish a safety that is superior to the combination therapy.

(3) Can the double antibody replace the monoclonal antibody?

It may be too early to assert that double antibodies can replace monoclonal antibodies in the future.

Clinical problems:

Efficacy problem: M7824 is not an exaggeration to describe it as "raise a tall building, entertain guests, and the building collapsed".

However, 2021 can be described as M7824's Waterloo, and a number of clinical failures cast a shadow over M7824.

Safety issues: Although dual-antibody drugs are expected to significantly improve the efficacy, their safety issues should not be underestimated, especially the dual-antibody drugs that target CD3 T cell recruitment.

Commercialization issues:

The price of double-antibody drugs may be a major bottleneck in their commercialization.