Jeff Fischer, President of Longhorn Vaccines & Diagnostics, discusses the evolution of antibody therapies from early serum treatments to targeted monoclonal antibodies, their impact on disease prevention and treatment, and the growing acceptance of antibody-based alternatives to traditional vaccines.

Antibody therapy has been used to prevent and treat disease for over 135 years. The first Nobel Prize in medicine went to Emil von Behring for his work on serum therapy to prevent and treat diphtheria. Antibody therapy has progressed from anti-serum from patients known to be infected with a pathogen, to serum screened for specific antibodies, to recombinant monoclonal antibodies (mAbs), and in the last decade extended half-life mAbs and multi-target antibodies. The first mAb was approved in 1986 to prevent organ transplant rejection. Over 150 antibodies are currently approved, including over 50 antibodies in new categories like antibody-drug conjugates, bispecific antibodies, extended half-life and other combinations.

mAbs have revolutionised modern medicine by offering targeted treatments for various diseases. These therapies work by providing directed antibodies to key antigens on tumours or pathogens, as well as cytokines and other immune system components, and engaging and in some cases modulating the immune system. As we delve into the development, current uses and future potential of antibody therapies, it becomes clear that these treatments continue to hold immense promise for improving patient outcomes and addressing unmet medical needs, as these antibodies can be positioned to address a variety of disease targets for both prevention and treatment.

How are antibody therapies developed?

The development of antibody therapies involves several critical steps. Initially, researchers must identify a molecule that is involved with a critical cellular or immunological action. Antibodies to the selected antigen may be produced in animals, or be produced using cellular or molecular platforms. These antibodies are screened and selected for their ability to target the antigen effectively. Once identified, the antibodies are cloned and produced in large quantities using cell culture techniques. This process ensures that the antibodies are specific to the target antigen and can effectively induce the required action.

How are antibody therapies used?

Antibody therapies are currently used to treat a wide range of conditions, including cancers, autoimmune diseases and infectious diseases. One notable example is Beyfortus (nirsevimab), a mAb designed to protect against respiratory syncytial virus (RSV) in infants and young children. RSV is a significant cause of respiratory illness in this population, as well as in adults over age 60. Beyfortus works by providing passive immunity, introducing ready-made antibodies into the bloodstream to neutralise the virus before it can cause severe illness. Like its predecessor, Synagis (palivizumab), Beyfortus has been shown to significantly reduce the risk of severe RSV-related illness in at-risk, pediatric populations, demonstrating the capability of antibody therapies in preventing and treating infectious diseases. These targeted antibodies work with the body’s immune system whether fully intact or compromised.

In late 2023, Beyfortus was launched into the early childhood market, at a time that vaccine skepticism was growing. Sanofi, which sells Beyfortus, was unable to keep up with demand in the United States because they underestimated the level of support from both doctors and parents. While a new drug, it had several characteristics that differentiated it from vaccines that were falling out of favour. Synagis had almost 20 years of efficacy and safety data, and the previous RSV season had been especially severe and was in the news for months. The most significant characteristic is that antibodies provided a high degree of efficacy for a four to six-month period and cleared the body completely within a year with no residual effect. This process leaves the immune system as it would have if it was beginning to naturally develop immunity to the RSV pathogen.

The high uptake of Beyfortus for preventing RSV in newborns underscores an untapped potential of antibody therapies as being widely accepted disease prevention tools, even among those skeptical of traditional vaccines. In contrast, traditional RSV vaccines for elderly adults, like ABRYSVO, AREXVY and mRESVIA, have been less accepted, with only about 47% of people over age 751 receiving the therapies in the United States. Many adults aged 60 and older are not getting the RSV vaccine due to a lack of knowledge about RSV and the vaccine itself, as well as a lack of provider recommendation2. The success of Beyfortus highlights the opportunity for antibody therapies to be used successfully in other disease states, providing an alternative to traditional and mRNA vaccines.

The safety profile of mAbs is well understood and is more specific to the antigen it blocks. The US Food and Drug Administration (FDA) has a long history of approving these therapies for use in cancer and other autoimmune, inflammatory and infectious diseases. In the oncology space, mAbs have been used to target specific cancer cells, sparing healthy cells and reducing side effects compared to traditional chemotherapy. Herceptin (trastuzumab) targets the HER2 protein, which is overexpressed in some breast cancers, leading to improved survival rates for patients with HER2-positive breast cancer. Similarly, immune checkpoint inhibitors, such as Keytruda (pembrolizumab), have revolutionised the treatment of different cancers by blocking proteins that prevent the immune system from attacking cancer cells.

The promise of future antibody therapies

With a renewed focus on preventing acute and chronic illness while minimising side effects, antibody-based treatments make a firm case as a promising option for future therapies that can target many disease areas. Longhorn Vaccines & Diagnostics is currently working on antibody therapies to aid in the prevention of acute and chronic conditions caused by key bacterial toxins, as well as viral and bacterial diseases, including tuberculosis.

The benefits of targeted and effective treatments make antibody therapies a vital component of modern medicine. Operation Warp Speed3 demonstrated how quickly and safely mAbs therapies can be developed and delivered. Just as serum therapy in the late 1800s filled the void until vaccines could be developed, antibodies can play a key role in improving health while new technologies build the long-term safety and efficacy profiles that are crucial for widespread use.

References
  1. https://www.cdc.gov/rsvvaxview/data/adults-60-coverage-intent.html
  2. https://www.fiercepharma.com/manufacturing/sanofi-azs-infant-rsv-med-beyfortus-short-supply-rsv-season-brings-surging-demand
  3. https://www.gao.gov/products/gao-21-319
Biography

Jeff Fischer, MBA, President of Longhorn Vaccines and Diagnostics, is responsible for oversight of all non-scientific aspects of the organisation to include regulatory affairs. Fischer co-founded the company and served as its Chief Financial Officer from 2007-2017. From 1998-2005, Fischer served as an executive vice president and CFO in the biotechnology industry. He is a former infantry officer in the United States Marine Corps and holds an MBA from the University of Texas at Austin.