In terms of clinical studies, the human monoclonal antibody (mAb) sector is expanding faster than any other class of mAb therapeutics. The “chimeric” quality of some mAbs allows for a range of exciting developments. Many combine human DNA sequences with those of rodents or strands found in bacteriophage viruses, choosing only the ideal expressions.
These approaches were a long time in the making. First developed nearly forty years ago, mAbs overcame its initial hurdles during a technological growth spurt in the 1990s. Innovations in molecule generation transformed the sector, and in 2002 adalimumab became the first human mAb approved for clinical use by the US Food and Drug Administration (FDA).
Many more mAbs have followed suit, each one presenting potential benefits as well as challenges. They are an increasingly popular treatment option for an ever-expanding list of disorders. Yet while their overall success rate continues to rise, the approval rate of individual approaches fluctuates dramatically. It is important to keep this variance in mind when evaluating current developments in the mAb field.
While most human mAbs are designed to treat immune system disorders and various forms of cancer, the potential applications are endless.
Immunomodulatory human mAbs are often developed to treat serum factors, those proteins responsible for cellular regeneration, growth, and death. Interleukins are another common target of these mAbs, as the proteins that control immune responses are highly susceptible to disorders. Certain other health conditions can cause the immune system to release substances known as cytokines, and mAbs prevent them from affecting unrelated cells. With an overall success rate of 33 percent in clinical studies, the school of immunomodulatory human mAbs has the highest average in the field.
Antineoplastic human mAbs are primarily developed to treat the epidermal growth factor receptor (EGFR) protein, as it greatly impacts cellular mitosis and growth. EGFR research has remained popular for the past thirty years, but unfortunately the success rate of antineoplastic human mAbs remains at a modest 15 percent. Nevertheless, few receptors are as closely monitored and studied for their anticancer potential.
Beyond applications for immune system disorders and cancer, to date 18 human mAbs have been developed to target infectious diseases. Some go after bacterial antigens, but most are targeted toward viral hepatitis, rabies, HIV, and other viral infections. Candidal heat shock protein 90, a molecular chaperone released during certain infections, is also a human mAb target.
Another approach is to combine multiple mAbs into a single treatment, which has its own set of complications as well as potential rewards. Sector-wide, human mAbs have an average approval rate of just over 17 percent, but recent developments in the field may soon improve that figure.
Two different types of mAbs display great potential.
Bacteriophage viruses are the key to one increasingly popular approach. By facilitating recombinant expressions of certain antigen-binding fragments within a virus and monitoring the resulting fragments, researchers are able to identify the optimal antigen-binding traits.
The success rate for this approach has yet to reach 13 percent, but as the subsector expands the approval rate will presumably climb. To date the FDA has only approved one phage-derived mAb, with two more pending, but there are 32 more deemed viable for clinical trials.
Transgenic mouse technologies represent the second mAb frontier. Rodent hybridomas are cultivated in lab settings by fusing myelomas, a certain type of tumor cell, with antibody-producing cells. These hybridomas yield a regular supply of monoclonal antibodies, allowing for more experimentation and variation than human mAbs.
While unadulterated human-derived mAbs were initially considered to be a great success, in recent years their approval rate has dropped far below that of rodent-derived mAbs. With a 29 percent success rate, rodent-derived mAbs boast the highest success rate of any mAb, including the collective average of all human mAbs.
As history demonstrates, however, the initial successes of a new approach are no guarantee it will prove most efficacious in the long run. Rodent-derived mAbs hold undeniable potential, but further research and experimentation is required to fully realize it.
The same holds true of phage-derived human mAbs. Their initial clinical trials are promising enough that if their current approval rates are maintained throughout the next few years of research and development they may even eclipse human and rodent-derived mAbs.
Be they derived from human, rodent or bacteriophage sources, mAbs present intriguing possibilities in the fight against immunological disorders, cancer, and infectious disease. As these three afflictions are collectively responsible for the majority of fatalities around the globe, new mAb approaches represent far more than simply a new form of therapy. If the success rates of these innovative mAb therapies continue to rise, we may see a monumental surge in survival rates and life expectancies around the world.