Biosimilar Monoclonal Antibodies

Biosimilar monoclonal antibodies are highly comparable in both structure and function to already-approved biologics (also known as reference products). They include antibodies developed for therapeutic use, typically as more affordable alternatives to existing antibody drugs that are coming off-patent, and antibodies that are intended as research use only (RUO) products. RUO biosimilar antibodies are valuable tools for scientific discovery as they allow researchers to study the effects of therapeutic antibodies without having to source the original products, which can be prohibitively expensive and are often only available in large quantities. RUO biosimilar antibodies are used in a broad range of research applications. These include techniques such as flow cytometry, ELISA, and immunohistochemistry (IHC), as well as various pharmacokinetic (PK) studies, functional assays, and real-time label-free protein binding analyses such as surface plasmon resonance (SPR). A main reason for using methods like SPR to study biosimilar antibodies is to guide the development of new lead candidates based on binding affinity and kinetics. For example, a biosimilar antibody and a novel antibody molecule may have similar affinity (KD) for the target of interest but exhibit different rate constants of association (ka) and dissociation (kd), which can help to inform whether the new biologic is likely have better efficacy in vivo. Functional characterization of biosimilar antibodies encompasses many different types of assays. Commonly used methods include antibody-dependent cell-mediated cytotoxicity (ADCC) assays, whereby antibody binding to a target cell (e.g., a tumor cell) results in its cytolysis by an Fc receptor bearing effector cell (e.g., a natural killer cell), and complement-dependent cytotoxicity (CDC) assays, during which binding of the C1q complement protein to the antibody Fc region triggers activation of the complement cascade and formation of the membrane attack complex (MAC) to cause cell lysis. Biosimilar antibodies are also used for anti-drug antibody (ADA) assays, which involve testing patient samples to evaluate the immunogenicity of the original drug and gain insights into its safety and efficacy. Examples of RUO biosimilar antibodies that are currently being used by researchers include versions of Natalizumab, an α4-integrin antagonist used to treat multiple sclerosis (MS) and Crohn’s disease; Rituximab, an anti-CD20 antibody used for treating non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL); and Trastuzumab, a human epidermal growth factor receptor 2 (HER2) targeted therapy for patients with breast cancer.