The Potential of Biologics – What Does the Future Hold?

Biologics – therapeutic agents derived from natural components and/or sources – represent the future of medicine and medical research due to their targeted efficacy and tolerability.1 While humans have been using biologics for millennia and producing them using industrial methods for decades, it has been only recently that the true potential of biologics has become somewhat understood.2

Building blocks: how basic research paves the road to the clinic

While much of the excitement surrounding biologics is focused on the clinical impact, basic research quietly remains pivotal to biologics development. The primary advantages presented by biological agents – their malleability and their selectivity – both must be first discovered, investigated, and characterized in the laboratory. Moreover, optimizing biologics production requires comprehensive research to identify the best attributes for production models. Finally, and perhaps most importantly, the work done by basic research scientists in furthering the depth of our understanding of the systems and mechanisms that govern health and disease is absolutely essential to the identification of new therapeutic targets and biologic agents.3

Cracking the code: how genetic engineering changes biologics today

The ability to change the human genome was revolutionary in that it gave scientists the ability to design and produce custom biologic agents and production models. To this end, genetic engineering has been instrumental in the conception, generation, and testing of custom engineered cells used in cell therapy research (e.g., CAR-T cells, induced pluripotent stem cells). It has also been critical for the ongoing development and production of small molecule biologics with customizable sequences, such as receptors and antibodies, leading to the development and clinical trialing of dozens of unique antibodies designed to selectively target key mediators of disease, such as oncogenic cells (for cancers) and immune cells (for autoimmune diseases).

Genetic engineering also meant that genetic material could now be used as biologic agents in their own right – introduced into the body in order to modulate a deleterious mutation. Since 1989, over 2,000 gene therapy clinical trials have taken place around the world, focusing primarily on cancer, given the disease’s reliance on mutations for pathogenesis, but also investigating, in considerable depth, cardiovascular, infectious, and monogenic (caused by a single gene mutation, e.g., cystic fibrosis, Huntington’s disease) diseases and disorders.4 Although initial results did not match the lofty expectations of researchers and clinicians, the number of trials initiated per year has steadily increased, and researchers have been spurred by the approval of the first gene therapy in the EU in 2012 and the USA in 2017.4,5 

Today, the recent development of more powerful and easier-to-use gene editing tools, such as CRISPR, has further revolutionized biologic agent development and gene therapy research. The power and simplicity of the CRISPR/Cas9 system has greatly increased the number of researchers now logistically capable of performing biologics research, as well as their throughput potential.6

Fitting in: biologics guiding regenerative medicine

Scientists have dealt successfully in the molecular and cellular realms for many decades, but tissue- and organ-level repair has remained elusive. The exponentially increased complexity when dealing with a system rather than an individual entity, combined with the difficulties in mimicking the plasticity of tissues and organs as they respond to changing environmental conditions, has proved to be a considerable obstacle. Indeed, early attempts to simply introduce healthy cells into damaged or dead tissues were met with low retention and poor integration.7 Now, armed with more knowledge of the multiple facets involved in the natural healing response, an improved understanding of the importance of the microenvironment and extracellular matrix to cellular behavior, and superior cell reprogramming and genetic engineering tools, scientists are developing biomaterial scaffolds and matrices to promote cell integration and direct cellular behavior upon implantation. However, much remains to be investigated concerning the host-biomaterial relationship.8

From recognition to reality: fulfilling the potential of biologics

Continued progress in the fields of biotechnology, genetics, and cell biology have contributed to an exponential expansion in the identification of potential therapeutic targets and the derivation of methods for the modulation of these targets,2 and it’s unsurprising that biopharmaceuticals represented the fastest growing sector in the pharmaceutical industry as of 2014, with a growth rate twice that of conventional synthetically-derived agents.9 As biotechnology and bioengineering continue to add to the scientist’s toolbox, the combination of basic research, translational studies, and clinical trials will continue to devise, investigate, and test additional agents, techniques, and therapeutic avenues.

References
  1. M. McCamish et al., “Biosimilars: biologics that meet patients' needs and healthcare economics,” Am J Manag Care, 22(13 Suppl):S439-S442, 2016. 
  2. T. Morrow and L.H. Felcone, “Defining the difference: what makes biologics unique,” Biotechnol Healthc, 1(4):24-29, 2004.
  3. R.C. Mohs and N.H. Greig, “Drug discovery and development: Role of basic biological research,” Alzheimers Dement (NY), 3(4):651-657, 2017.
  4. E. Hanna et al., “Gene therapies development: slow progress and promising prospect,” J Mark Access Health Policy, 5(1):1265293, 2017.
  5. US Food and Drug Administration (2017, August 30). FDA approval brings first gene therapy to the United States [press release]. Retrieved from: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm574058.htm
  6. L. Cai et al., “CRISPR-mediated genome editing and human diseases,” Genes Dis, 3(4):244-251, 2016.
  7. J. Bartunek et al., “Delivery of biologics in cardiovascular regenerative medicine,” Clin Pharmacol Ther, 85(5):548-552, 2009.
  8. R. Londono and S.F. Badylak, “Biologic scaffolds for regenerative medicine: mechanisms of in vivo remodeling,” Ann Biomed Eng, 43(3):577-592, 2015.
  9. N. Davies, “The future of biologics,” The Pharma Letter, 17 April 2017, Retrieved from: https://www.thepharmaletter.com/article/the-future-of-biologics (accessed November 27, 2018)
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