Genetic Engineering & Biotechnology News

JUN15 2018

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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28 | JUNE 15, 2018 | Genetic Engineering & Biotechnology News | optimize a disparate range of fields, from surgery to commercial air flight. AMP recommends that when data files get transferred between the DNA sequencer and the data center and the cloud service provider and the server that someone verify that the transferred files are identical to the originals, as files are known to get truncated during transfers without personnel being aware of the truncation—a problem that has very obvious and troubling ramifications. Another recommendation is to give each sample identifiers that relate to the location, as well as to the patient and the sample, since different labs in different locations can use the same sample identifiers. This safeguard can help ensure that sample in- formation is maintained from start to finish, throughout the entire pipeline of analysis beginning with sample collection and end- ing with a patient report. "NGS and especially bioinformatics is so rapidly evolving, it is hard to keep up," notes Dr. Roy. This is as true for his team develop- ing guidelines as it is for doctors treating pa- tients, and researchers searching for molecu- lar targets and the drugs to target them. Peter K. Schulz-Knappe, M.D., and Georg Lautscham, Ph.D. Immunotherapy represents the most prom- ising approach to cancer treatment since the advent of targeted therapies. The goal of any immunotherapeutic drug is to boost the body's immune response to fight can- cer. Examples of this type of treatment in- clude immune checkpoint inhibition (ICI), which releases the "brakes" tumors apply on the immune system; chimeric antigen receptor (CAR) T-cell therapy, which di- rects T cells to tumor antigens; cytokine immunotherapy, which activates signal- ing pathways that heighten the immune response; and therapeutic cancer vaccines, which help the immune system recognize and destroy cancer cells. Many novel immunotherapeutic drugs and combination therapies are in develop- ment and responsible for an explosion of clinical trial numbers—far beyond 1000. Today, multiple ICI therapies have received marketing authorization, with an entire gen- eration of novel therapeutics due to reach the market over the next few years. A recent report has estimated that the value of the global market for cancer immunotherapy will rise to $75.8 billion by 2022. 1 Although immunotherapies are highly effective in some patients, many patients do not respond to treatment or suffer from in- flammatory side effects known as immune- related adverse events (irAEs). These toxici- ties frequently lead to the discontinuation of treatment and sometimes cause severe dam- age to the patient. The future development of effective and safe therapies will, therefore, rely on our ability to predict and minimize these irAEs. Upsetting the Immune Balance The incidence of irAEs is known to com- promise clinical drug development, as well as jeopardize the use of cancer immunothera- pies within the marketplace. In clinical tri- als, patients may decide—or be required—to discontinue their participation, and (as ob- served recently) regulatory bodies may inter- vene and halt trials due to such irAEs, even when anticancer effects are observed. 2 Gen- erally, patients may miss experiencing immu- notherapy's benefits while still risking severe toxicities—and the loss of valuable time that could have been devoted to an alternative and potentially better therapy. Today, irAEs are largely associated with ICI therapies and arise by virtue of ICI mechanisms of action. The physiological role of immune checkpoints, such as CTLA- 4 and PD1/PD-L1, is to act as negative im- mune regulators (brakes) of autoreactive T cells, resulting in immune tolerance and the prevention of autoimmunity. However, once checkpoints are blocked, and these brakes released, the resulting activated T cells can cause an overstimulation of the immune sys- tem, leading to a widespread inflammatory autoimmune response. It is also worth men- tioning that patients with a history of serious autoimmune disease are typically excluded from immuno-oncology trials, based on these patients' increased risk of toxicities. 3 irAEs can range in severity from non-life- threatening conditions, such as skin rash, to more serious complications involving the joints, endocrine glands, lungs, liver, and other organs. Because there are currently few standardized diagnostic criteria for irAEs, there is a concern that their incidences are underreported, making it difficult to assess the impact they may have on patients. Although some of these irAEs can be Protagen Believes Immuno-Oncology Must Predict and Minimize Immune-Related Adverse Events Prevent Cancer Immunotherapy's Side Effects Molecular Diagnostics Continued from page 27 Translational Medicine Figure 1. Several autoantibodies are differentially expressed in patients who develop irAEs (A) compared to those who do not (B), demonstrating the role autoantibodies can play in confirming and predicting the incidence of irAEs. Current immunotherapy agents plotted on Gartner's Hype Cycle, showing their placement along the five key phases of a technology's life cycle: the Technology Trigger, the Peak of Inflated Expectations (hype), the Trough of Disillusionment, the Slope of Enlightenment, and the Plateau of Productivity. Starting in 2014, many have surmised that a new Technology Trigger and Peak of Inflated Expectations has begun. Anderson Cancer Center

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