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  • Carrie Printz

Immunology Translational Research “Dream Team” Receives Funds to Conquer Cancer

A team of investigators from several leading U.S. cancer research institutions will receive $10 million over 3 years to develop new ways to harness the body's immune system in the fight against cancer.

The project, “Immunologic Checkpoint Blockade and Adoptive Cell Transfer in Cancer Therapy,” is funded by Stand Up to Cancer (SU2C) and the Cancer Research Institute (CRI). SU2C, a program of the Entertainment Industry Foundation, is administered by the American Association of Cancer Research (AACR), and was formed in 2007 to speed the pace of groundbreaking translational research by funding “dream teams” to collaborate on projects. CRI funds cancer immunology research.

The team's goal is to explore combinations of promising immunotherapies and techniques known as immune checkpoint blockade and adoptive T-cell transfer, according to team co-leader James Allison, PhD, chairman of the department of immunology at the University of Texas M.D. Anderson Cancer Center, based in Houston, Texas. The other team leader is Antoni Ribas, MD, PhD, director of the tumor immunology program area at the Jonsson Comprehensive Cancer Center at the University of California at Los Angeles.

Participating institutions also include Johns Hopkins University, the Fred Hutchinson Cancer Research Center, the Dana-Farber Cancer Institute, the California Institute of Technology, Memorial Sloan-Kettering Cancer Center, and the Netherlands Cancer Institute.

“We've been trying to get the immune system to attack cancer for a long time,” Dr. Allison says, noting that advances in the field within the past 2 years have shown particular success in “reeducating” patients’ immune systems to fight their cancer.

Adoptive T-cell therapy, for example, involves expanding white blood cells known as T lymphocytes outside the body, engineering them to be more effective, and infusing them back into patients to attack their cancer. At the same time, these lymphocytes have pathway “checkpoints” that stop immune responses. Cancers use these checkpoints to resist immune attacks. Scientists have found that blocking these checkpoints with specific antibodies can enable the immune system to do its job.

The research team will evaluate checkpoint expression in patients’ tumors before and after adoptive cell transfer, and/or checkpoint blockade, and also test the theory that many T lymphocyte targets occur in the tumor. They also will test several promising drugs in small, pre-surgical clinical trials, set to start in 2014.

“We know now that mobilizing the immune system to attack tumor cells works,” Dr. Allison says. “Down the road, we want to combine these treatments with new targeted therapies, which lead to rapid tumor reduction, but are short-lived because the tumor eventually becomes resistant.”

Dr. Allison's hope is that at the end of the 3-year project, scientists can begin such combination clinical trials. “It's not just a dream,” he says. “We think it can be a reality. That's our goal.”


Researchers are exploring new combinations of immunotherapies and techniques designed to trigger the body's immune system to attack cancer cells.

NIH Program Helps Investigators Advance Their Research

Research into new treatments for cancer, spinal cord injury, and rare diseases is getting a boost through an initiative at the National Institutes of Health (NIH).

The program, Bridging Interventional Development Gaps (BrIDGs), gives researchers access to both resources and expertise at no charge, according to John McKew, PhD, acting director of the NIH's National Center for Advancing Translational Sciences’ (NCATS) Division of Pre-Clinical Innovation. It is supported by the NIH Common Fund.

“There are a number of molecules discovered in academia and small companies with interesting efficacy data, but that don't have the money to progress through,” Dr. McKew says. “What you would need is pre-clinical development to enable a clinical trial.”

Rather than fund applicants directly, BrIDGs enables NIH contractors to provide preclinical services, such as toxicology studies, so that investigators can have demonstrated efficacy in a disease model. Such preclinical efforts can become expensive very quickly, and that is the stage where many projects get stalled, Dr. McKew notes.

With many of these molecules in limbo due to a weak venture funding environment, BrIDGs offers an alternative for investigators to pursue a path toward drug development. Once applicants are selected, program representatives meet with them to examine their data and determine the necessary steps to create a data package used in the filing of an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA). Clinical trials of an investigational new drug can begin within 30 days of an IND, unless the FDA says the IND is subject to a clinical hold.

The program, known as NIH Rapid Access to Interventional Development before it came under NCATS’ jurisdiction a couple of years ago, has had 224 applicants since it began in 2005. In all, 37 projects have been approved, including 19 that have been completed, and 13 that have submitted INDs. According to Dr. McKew, 12 of those submissions are now in clinical trials.

In addition, third-party companies have licensed all but 6 of these agents.

“That's really what we're trying to do, ‘de risk’ these molecules by generating enough data to encourage outside investment,” Dr. McKew says.

BrIDGs’ portfolio includes molecules targeting a wide range of diseases, such as multiple sclerosis, epilepsy, cancer, and rheumatoid arthritis. Among its selected projects in 2012 were:

  • Tumor Penetrating Micro-particles for Peritoneal Cancers, Jessie Au, PhD, Optimum Therapeutics, LLC, San Diego, California. A drug delivery system is under development to target peritoneal tumors.
  • Development of Assays to Detect Anti-Drug Antibodies Against ACP-501 (recombinant human ACP lecithin-cholesterol acyltransferase [LCAT] deficiency syndrome), Brian Krause, PhD, Alphacore

    Pharma, LLC, Ann Arbor, Michigan. The objective is to develop a treatment that would act as a replacement therapy to offset the drastic reduction in high-density lipoprotein (HDL) cholesterol levels caused by this rare disorder.

  • Development of Nogo Receptor Decoy for the Treatment of Spinal Cord Injury, George Maynard, PhD, Axerion Therapeutics, Inc., New Haven, Connecticut. The project involves developing a compound (Nogo Receptor Decoy) to rewire nerve cells that promote the recovery of neurological function. The NIH's National Institute of Neurological Disorders is co-funding this work.

BrIDGs solicits applications annually. For more information about the program, see www.ncats.nih.gov/bridgs.html.


A federal funding program is helping researchers bring drugs aimed at treating multiple sclerosis, cancer, and rare diseases into the preclinical development phase.

New FDA Law Seeks to Speed Development of Breakthrough Drugs

Two drugs designed to treat cystic fibrosis were the first to receive “breakthrough therapy” designations by the U.S. Food and Drug Administration (FDA) in January under a new program meant to speed the development of drugs for serious or life-threatening illnesses.

The drugs, produced by Cambridge, Massachusetts-based Vertex Pharmaceuticals, are ivacaftor monotherapy and the combination regimen of the drug VX-809 with ivacaftor. The Breakthrough Therapy Designation program was enacted as part of the 2012 U.S. Food and Drug Administration Safety and Innovation Act (FDASIA). Its intent is to expedite the development and review of potential new drugs if there is preliminary clinical evidence that the drugs may show substantial improvement over current therapies.

This option complements 3 existing FDA programs to speed up drug development: Fast Track, Priority Review, and Accelerated Approval. Although similarities exist between Fast Track and Breakthrough Therapy in terms of speeding the development of drugs for serious conditions, there are some key differences. For example, the FDA will provide more intensive guidance from senior management on an efficient development program for drugs designated as breakthrough therapies, according to an FDA spokesperson.

The agency's involvement in these efforts will include:

  • Meeting with the sponsor and the review team throughout the development of the drug.
  • Providing timely advice to the sponsor regarding the development of the drug to ensure efficiency in data gathering.
  • Involving senior managers and experienced review staff in a collaborative review.
  • Assigning a cross-disciplinary project lead for the FDA review team to ensure an efficient review and serve as a scientific liaison between the team and the sponsor.
  • Ensuring efficient design of the clinical trials, such as minimizing the number of patients exposed to a potentially less effective treatment.

At press time, the FDA had received a total of 15 Breakthrough Therapy Designation requests, of which 3 had been denied, 2 had been granted, and 10 were pending. The agency is currently developing guidelines for the pharmaceutical industry regarding breakthrough therapies.

Vertex Pharmaceuticals received a Breakthrough Therapy Designation for ivacaftor for possible indications beyond its current approved use in cystic fibrosis patients with the G551D mutation. The Breakthrough Therapy Designation for the combination regimen of VX-809 with ivacaftor was based on the Phase 2 clinical trial data announced in 2012.


The FDA has fast-tracked the development of two novel drug treatments for cystic fibrosis under the agency's new Breakthrough Therapy Designation program.

Nanoparticles Target Multiple Sclerosis, Other Autoimmune Diseases

For some 30 years, Stephen Miller, PhD, and colleagues have been researching how to induce specific immune responses in the treatment of autoimmune diseases without damaging patients’ entire immune system and making them more susceptible to infections, or even cancer.

“There are literally several hundred autoimmune diseases directed against every system in the body,” says Dr. Miller, a professor of microbiology-immunology at Northwestern University in Evanston, Illinois. “What we've learned over the years is that if you take the antigens targeted against a specific autoimmune response—such as multiple sclerosis (MS)—and inject them into mice, we can prevent and treat the disease.”

In MS, the immune system attacks the myelin membrane that insulates nerve cells in the brain, spinal cord, and optic nerve. When that insulation is destroyed, symptoms can range from mild limb numbness to paralysis or blindness.

Dr. Miller and colleagues recently completed a Phase 1 clinical trial revealing that investigators can safely infuse antigen-coupled apoptotic cells into patients and inhibit the immune response against myelin without inhibiting other immune responses.

Additionally, investigators realized recently that rather than using a patient's own cells, they could attach the myelin antigens onto nanoparticles, infuse them into mice, and create an even more “robust tolerance,” according to Dr. Miller.

The biodegradable nanoparticle—which is 200 times smaller than a human hair—is readily produced in a laboratory and standardized for manufacturing. It is made of a polymer called Poly(lactide-co-glycolide) (PLG), which consists of lactic acid and glycolic acid, both natural metabolites in the human body. PLG is FDA-approved for other applications, too.

“It's a universal carrier, that by simply changing the antigen you put on it has the theoretical possibility of targeting any different autoimmune disease,” Dr. Miller says. “It also can be attached to environmental antigens that cause asthma and allergies.”

The nanoparticle was developed by Lonnie Shea, PhD, a professor of chemical and biological engineering at Northwestern University. She and Dr. Miller were contributing authors on a study demonstrating the success of the nanoparticle in targeting a model of relapsing remitting MS in mice. The paper was published in the November 18, 2012 issue of Nature Biotechnology.

Dr. Miller and his colleagues also are exploring the nanoparticle's applications in diabetes. They are partnering with nonprofit organizations such as the Juvenile Diabetes Foundation to reach out to biotech and pharmaceutical companies that may wish to sponsor additional research. Dr. Miller anticipates that clinical research with the nanoparticles is probably about 3 to 4 years away.

“Based on all the other ways we've studied, this method works by far the best and the most efficiently,” he adds.


Scientists have developed a nanoparticle designed to inhibit the immune response triggered by multiple sclerosis to attack the myelin membrane insulating nerve cells in the brain, spinal cord, and optic nerve.