A single tool is being wielded to tackle cancer, autoimmune disease, and even the most elusive itch receptors, serving as a blueprint for one of the most innovative modern medical technologies: antibodies. 

Monoclonal antibodies, or antigen-binding proteins produced in the laboratory, are Y-shaped molecules’ primary pharmaceutical purpose is to inhibit or mark certain proteins on cells, allowing them to neutralize threats or flag them for destruction by the immune system. Constituting a $242.6 billion industry as of 2024, the monoclonal antibody market size is projected to grow to $412.1 billion by 2029, according to Boston headquartered BCC Research, a leading global market research company providing market analysis.

Monoclonal antibodies belong to a broader drug class called biologic medicines, biologics for short, that originate from living organisms or biological processes. Biologics like antibodies often require more resources and complex biotechnological methods to synthesize. These intricacies limit the widespread accessibility of antibodies, despite the promising scientific innovation in the field, thus providing potential for new innovative technologies to transform the antibody landscape.

Why Biologics?

Biologics and small molecule medicine constitute the two main categories of pharmaceutical drugs. The common small molecule medicines – antibiotics, antihistamines, and painkillers such as aspirin – are perhaps the more familiar group of drugs to the mainstream eye as one of the first things that comes to mind when thinking of pharmaceuticals. They also tend to be more easily producible and scalable.

However, the simplicity of small molecules also serves as their drawback. Small molecule drugs have a limited scope, less useful in the treatment of complex illnesses, not to mention that it is much rarer to develop resistance against biologics than small molecule drugs. While biologics tend to be larger and more complex molecules, this lends to an unmatched specificity and utility. Furthermore, antibodies are much more specific to intended targets and are effective on the immune-system level as well as in cell signaling pathways. Far from one-trick ponies, antibodies have an incredible versatility in terms of form and application.

Applications

One of the most promising areas for antibody development is oncology. Antibodies can be engineered to bind to unique proteins on cancer cells or inhibit growth signals. Currently, 6-13 cancer antibody therapeutics are approved by the FDA and EMA annually. Trastuzumab, one of the most popular antibody cancer pharmaceuticals on the market, operates by binding to the active site of the HER2 protein found in high levels on breast cancer cells, blocking the proliferation of cancer cells.

Another way that antibodies can be used in oncological therapy is through antibody-drug complexes, or ADCs, that use the specificity of antibodies to deliver cytotoxic drugs, mitigating the effects of off-target binding of the drug alone. 

Beyond oncological applications, the concept of flagging and inhibiting proteins can be especially useful in treating autoimmune diseases. Rituximab targets B-cell marker CD20, allowing it to mitigate B-cells producing harmful antibodies that cause inflation in arthritis and polyangiitis.

Courtesy National Cancer Institute

Membrane proteins as a new frontier for antibodies

Philadelphia-based biotechnology company Integral Molecular was founded in 2001 and focuses on membrane protein technology. The research-based company has innovated significantly in the application of antibody technology to the “undruggable” membrane proteins embedded heavily into the cell membrane. Integral Molecular tackles these notoriously difficult targets to develop antibodies against, tapping into a market that comprises more than 60% of therapeutic targets.

The utility of membrane protein antibodies includes difficult targets involved in cancer cell-signaling pathways, diabetes and in other important diseases. One notable and recent breakthrough involves the GLUT4 protein, which allows glucose to enter cells from the bloodstream as a downstream effect of insulin binding to local receptors. Malfunctions in this process can lead to insulin resistance, closely linked to type 2 diabetes. Integral Molecular recently developed highly specific GLUT-4 antibodies, a tool that can not only be used to better study the GLUT-4 protein but also offers potential for future antibody-based therapies for type 2 diabetes. 

A key factor in Integral Molecular’s innovation is their combined strength in antibody discovery through off-shoot Cell Surface Bio, Paratope-PLUS antibody mapping, and Membrane Proteome Array off-target screening capabilities. Integral Molecular’s work in this underexplored field may yield even more important discoveries relevant to a wide range of diseases in the future.

Challenges

Despite their promise, antibody-based therapies come with significant hurdles, chief among them is the high cost of production. Necessitating large amounts of resources and time, the final products, no matter their effectiveness, may be out of reach for consumers. However, this is where investment and technological innovation can pave the way for greater accessibility of these products. 

One of Harvard University’s own immunologists, Dr. Thomas Springer, has invested over 210 million to fund the development of validated antibodies for scientific research at the Institute of Protein Innovation, a Boston-based nonprofit research institution that aims to increase access to antibodies. By developing synthetic and validated antibodies available to the global scientific community, IPI levels the playing field for the use of essential antibodies relevant in a wide variety of immunoassays and experiments. 

The implementation of artificial intelligence models may also aid in speeding the process of antibody discovery, which can help reduce the costs of manufacturing. A novel technology called AlphaFold is a machine learning program that has been able to predict protein structure, which can be utilized by companies to potentially reduce expensive lab experiment work by optimizing structure and predicting binding.

The feasibility of the implementation of machine learning in antibody discovery is being pioneered by Boston-area biotech company Generate:Biomedicines, which designs proteins from the ground up, utilizing deep learning to generate novel antibody protein sequences. Organizations like Integral Molecular, IPI, and Generate Biomedicines show that the next era of antibody therapeutics is well within reach, only limited by our willingness to provide the necessary scientific and monetary investments.

Our bodies have naturally protected us using antibodies against disease after disease over the course of human history. We are now intentional engineers of these defenses to tackle the health threats of the future.