Monoclonal and bispecific antibodies represent two distinct classes of therapeutic antibodies, each with unique characteristics and applications. Monoclonal antibodies (mAbs) target a single, specific antigen. In contrast, bispecific antibodies (bsAbs) are designed to bind to two different antigens simultaneously, offering a versatile approach to treatment by engaging multiple targets at once.
This article will illustrate the distinctions between monoclonal and bispecific antibodies in terms of structure, development and production as well as possible applications, highlighting the huge potential of both mAbs and bsAbs.
There are several ways in which monoclonal and bispecific antibodies can be distinguished. The FDA refers to the latter as “next generation monoclonal antibodies”1, but what makes them so different? We will describe their key differences in this article.
Monoclonal antibodies are lab-produced molecules which bind to a specific epitope on a single antigen.2 They are produced using cells lines derived from a single, unique parent cell, ensuring uniformity of the produced antibody.
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Bispecific antibodies, however, are more complex. These innovative molecules are designed to target two different antigens simultaneously, offering a dual mechanism of action.3 This capability allows bsAbs to bring together different cell types or pathways, enhancing their therapeutic potential.
Monoclonal antibodies possess a characteristic Y-shaped structure, consisting of two identical heavy chains and two identical light chains. Each arm of the Y contains an antigen-binding (Fab) region that targets a specific antigen, while the stem, or Fc region, mediates immune system interactions.4
In contrast, bsAbs can vary in structure. While some maintain the Y-shaped structure, they incorporate different Fab regions on each arm, allowing them to engage two distinct antigens simultaneously.5
Monoclonal antibodies are often produced using recombinant DNA technology and cell lines such as Chinese hamster ovary (CHO) cells. The production involves either transient transfection for rapid, short-term expression or stable transfection for consistent, long-term production.
Read more: Transient vs. stable transfection
Bispecific antibodies require more sophisticated engineering techniques. They often necessitate complex expression systems to ensure correct assembly and function of individual antibody components. Producing bsAbs in CHO cells involves advanced genetic modifications and stringent quality controls to achieve the desired dual functionality, making the process more intricate and resource-intensive compared to mAbs.
However, the challenges surrounding bsAbs start even earlier than production, as it can be difficult to determine which bsAb is most suited for a specific application. Pharma companies and CDMOs therefore rely regularly on the expertise of dedicated service providers to make the optimal choice.
Monoclonal antibodies are widely used in treating cancers, autoimmune diseases, and infectious diseases. They work by targeting specific antigens on diseased cells, facilitating immune-mediated destruction through mechanisms like antibody-dependent cellular cytotoxicity (ADCC). Furthermore, they are also widely used in research and diagnostics.
The applications of bispecific antibodies are widespread due to their ability to engage two different targets simultaneously. This dual targeting can enhance therapeutic efficacy, especially in complex diseases like cancer, where they can bridge tumor cells and immune cells to enhance anti-tumor responses.6
Examples of FDA-approved bispecific drugs demonstrate their growing importance in oncology and other fields.6 BsAbs currently being developed focus on treating infections, autoimmune, neurodegenerative and chronic inflammatory diseases, as well as ocular, vascular, and hematologic conditions.1
Monoclonal and bispecific antibodies each bring distinct advantages to the table. MAbs are highly specific, binding to a single antigen with great affinity. This precision makes mAbs ideal for targeting cancer cells, neutralizing pathogens, or modulating immune responses in autoimmune diseases. Their established production processes and well-characterized pharmacokinetics enhance their reliability and safety profiles.
BsAbs offer a versatile approach by targeting two different antigens simultaneously. This dual binding capability creates many advantages of bispecific antibodies, as it enables bsAbs to bridge immune cells to cancer cells, enhancing immune-mediated killing, or to modulate multiple signaling pathways in complex diseases.
For example, bsAbs can recruit T-cells directly to tumor cells. Additionally, bsAbs can reduce the likelihood of resistance by targeting multiple pathways simultaneously, making them powerful tools in oncology and beyond.6
Both monoclonal and bispecific antibodies open new avenues in research, diagnostics, and therapeutics. But while the advantages of bsAbs can be mainly traced back to their ability to bind to two different epitopes, mAbs have characteristics that make them the preferred choice in many situations.
In the table below, you can find the differences and similarities between mAbs and bsAbs at a glance.
Monoclonal Antibodies (mAbs) Bispecific Antibodies (bsAbs) Structure Uniform structure with two identical antigen-binding sites Variable structure with two different antigen-binding sites Development Often produced using recombinant DNA technology Requires advanced genetic engineering to combine two antigen-binding sites Production methods Utilizes standard methods such as transient transfection and stable transfection in CHO cells Additionally involves specialized production processes to ensure correct assembly and dual functionality Applications Used broadly in treating cancers, autoimmune diseases, and infectious diseases Especially advantageous in complex conditions like cancer, but also studied for vascular, ocular, and neurodegenerative diseases (among others) Advantages High specificity, well-characterized pharmacokinetics, well-established production processes Dual targeting capability, reduced likelihood of resistance
evitria is a trusted provider of high-quality recombinant antibody production services, ensuring a reliable supply for diverse research and therapeutic needs.
Specializing in rAbs, afucosylated antibodies, Fc-silenced antibodies, and bispecific antibodies, evitria leverages state-of-the-art CHO cell expression systems for optimal results. Our expertise in transient transfection allows for rapid, large-scale production of rAbs, meeting tight timelines with superior quality.
For bispecific antibody expression services, evitria offers comprehensive support from construct design to production, utilizing advanced formats like Duobody, IgG-scFvs, and Knobs-into-Holes. This ensures high yield and functionality, tailored to the specific needs of each project. Partnering with evitria ensures efficient, scalable, and reliable antibody supply, propelling scientific advancements and therapeutic innovations – from sequence to antibody in only 4 weeks.