An Online Wellness Magazine produced by The University of Texas Health Science Center at Houston (UTHealth)

Final Leg

Moving promising therapeutics into practice

Nicknamed the “valley of death” by insiders, the gap between academic discovery and drug development is where most good ideas for new drugs fall to the wayside. A commercial drug developer turned academic researcher, Zhiqiang An, Ph.D., has worked on both sides.

After 15 years in the pharmaceutical and biotechnology industry, mostly at Merck Research Laboratories, An was recruited to lead the Texas Therapeutics Institute (TTI), an academic drug discovery center at The University of Texas Health Science Center at Houston (UTHealth).

“We’re bridging the valley of death at TTI by providing critical drug development technology and expertise to the academic research community,” says An, the institute director. “The TTI has been successful in attracting more than $30 million in funding from federal, state and industry sources in support of drug discovery.”

Five drug candidates

The institute, An adds, has established two biotech spinoff companies and so far has licensed out five drug candidates targeting cancer and spinal cord injury to the biotech industry for further development.

The institute’s areas of expertise include antibody drug discovery. “Antibodies are a part of our natural immune system and they fight infectious diseases and cancer. The rapid rise of antibody-based therapies is largely due to their desirable safety profile, target specificity and efficacy,” says An, the Robert A. Welch Distinguished University Chair in Chemistry at McGovern Medical  School at UTHealth and a member of the faculty of The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences.

Therapeutic antibodies represent one of the significant advances in the history of medicine, according to An, who is recognized worldwide for his research in this area. In fact, he edited a go-to book on the field — “Therapeutic Monoclonal Antibodies From Bench to Clinic.”

“We help scientists translate their basic discoveries into new treatments,” An says. “Most of the therapeutic antibodies generated in academic laboratories do not advance beyond the basic discovery stage.”

Making the latest technology available to researchers

One reason, according to An, is that many researchers do not have access to the highly specialized protein engineering technologies. The TTI is making these antibody platform technologies available to Texas-based researchers and beyond.

First approved by the Food and Drug Administration in 1986 for human use, more than 74 of these antibody-based drugs are being used to fight cancer as well as immunological, cardiovascular and infectious diseases. Incredibly, at least 645 antibody-based drugs are in various stages of clinical testing, which accounts for a large portion of experimental drugs in clinical trials, An says.

So how do they work? Antibodies can be engineered to bind to disease targets including receptors on cell surfaces and circulating proteins. In addition, they can be designed to carry toxins and radioisotopes to kill cancer cells. Picture a miniaturized heat-seeking missile with a drug payload.

Antibody-based drugs are also a critical component in cell-based immune therapies.

How antibodies destroy tumors

When it comes to killing cancer cells, therapeutic antibodies can:

  • Block cancer signaling pathways,
  • Deliver a payload of cancer-killing toxins,
  • Cut off a tumor’s blood supply, and
  • Boost the immune system’s ability to fight disease.

“Many of the antibody-based drugs can possess more than one of these mechanisms to fight disease,” An says.

“Not limited to the treatment of disease, antibodies are also used to diagnose medical conditions by detecting disease biomarkers in cells, tissues, and in the human body,” An says. “Antibodies are extremely sensitive and specific to the disease biomarkers.”

When it comes to advancing promising treatments, An sees academia excelling in discovery and innovation. Pharma and biotech companies on the other hand have the development and commercialization expertise.

More than 100 scientific publications

Established in 2010 with the support of the Texas Emerging Technology Fund, The University of Texas System and UTHealth, the Texas Therapeutics Institute also conducts basic academic research, which is reflected in the 100 plus scientific publications by researchers in the institute.

Housed in UTHealth’s Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, the institute has 40-plus faculty members, postdoctoral fellows, graduate students and supporting staff.

An’s pharmaceutical contacts were instrumental in getting the Texas Therapeutics Institute off the ground. “When I started at TTI, I reached out to big pharma. I knew they were interested in collaborating with major universities,” An says.

Private industry funding

An's efforts led to about $6 million in private funding during his first five years with the institute. The institute has additionally received more than $11 million in funding from the Cancer Prevention & Research Institute of Texas (CPRIT), which began making awards in 2009 after Texas voters approved a 2007 constitutional amendment committing $3 billion to the fight against cancer.

Despite advances in cancer care, the disease still claims approximately 100 lives a day in Texas.

“We are confident that TTI will continue to grow and play a critical role in bridging the ‘valley of death’ in drug discovery and in advancing the biotech industry in Houston and the State of Texas,” An says.

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