Bispecific Antibodies: Emerging Novel Immunotherapies for Cancer

Therapeutic antibody drugs have recently experienced explosive growth due in large part to the fact that immunotherapies stimulate the immune system to attack cancer cells. Within oncology research alone, more than 20 therapeutic antibody drugs received FDA approval for new treatments or indications during 2015 to 2018. Additionally, more than 300 therapeutic antibody drugs are in ongoing clinical trials.

Bispecific antibodies are emerging as a novel approach for immunotherapies by combining two antigen-recognizing elements into a single construct that is able to simultaneously bind to two distinct targets. They can be applied to recruit immunological effector cells for killing tumor cells or to simultaneously block two signaling pathways or cytokines. Subsequently, they have prompted significant interest for a number of therapeutic applications, both in cancer and in other indications. The growing interest in therapeutic antibodies along with the rapid progress in antibody engineering have yielded a multitude of bispecific antibodies formats and derived molecules that differ in size, shape and function, sometimes referred to as a “Bispecific antibody zoo”. These bispecific antibodies can offer additional advantages:

• Provide superior potency due to novel mechanism of action
• Offer enhanced safety profile due to less off-target binding & lower dose - as seen in safety concerns in combination therapies
• More cost-effective as it only develops one molecule and saves half of investment in comparison to combination therapy

All these advantages of bispecific antibodies make them potential powerful treatments for patients and physicians. However, despite the numerous bispecific formats and benefits they have brought to patients, there are two major challenges in developing 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.

With these two major concerns in mind, Genscript has developed the SMAB bispecific format, which is a single domain antibody fused to a monoclonal antibody. The concept is very simple in that we will use all-natural components to realize bivalent and multivalent purpose. The major advantages with the SMAB platform are bio superiority, excellent developability for high yield and stability. SMAB Bispecific Antibodies demonstrated high affinity to the target cells in many models. In addition, the SMAB platform has several advantages over mono-specific therapeutics and other bispecific antibody designs, including:

• BsAbs show bio-superiority and a better safety profile over monotherapy or combinatorial therapeutics
• SMAB platform has good developability and therefore can generate high yields & concentration in formulation with desirable stability
• the SMAB platform has the same manufacturing process as conventional antibody therapeutics
• the sdAb in GenScript’s SMAB platform has the ability to bind to “hidden” epitopes, such as enzymes, ion channels, etc. as well as being highly flexible for the construction of multi-valent molecules using a “plug and play” fashion.

Amidst fierce competition coupled with many unmet medical needs, there is an urgent demand for new therapeutic strategies, such as combination therapy, and novel modalities, such as bispecific antibodies. In this interactive webinar, Genscript gives an overview on therapeutic antibodies, opportunities and challenges of current monotherapies and major benefits of bispecific antibodies and platforms.

---

GenScript serves as a partner for researchers in basic life sciences, translational and biomedical fields as well as early-stage drug development. With best-in-class capacity and capability in both technology and manpower, GenScript supports scientific endeavors through offering high-quality products and services. The diverse portfolio of GenScript encompasses extensive services in gene synthesis and molecular biology, peptide synthesis, protein expression and engineering, custom antibody development and engineering, animal model development, in vitro/in vivo pharmacology as well as variety of catalogue products. With the goal of “Making Research Easy”, GenScript has strived to remain a reliable research partner for scientists in over 100 countries across the globe.