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|Igor Dmitriev, PhD
The illustration shows an adenovirus particle carrying metals and antibodies for cancer therapy. In this case, the metal is copper-64, a radioactive metal useful for both imaging and cancer therapy. Antibodies shown in orange and purple can target the virus to specific tissues or tumor types.
Researchers at Washington University School of Medicine in St. Louis have received a $3 million grant from the National Cancer Institute (NCI) to develop a triple threat in the fight against cancer: a single virus equipped to find, image and kill cancer cells, all at once.
Led by David T. Curiel, MD, PhD, Distinguished Professor of Radiation Oncology, the program will build on his group's expertise with adenovirus, a virus that causes the common cold and has shown promise in cancer therapeutics and imaging.
"This is a virus that we know a lot about," says Curiel, director of the Biologic Therapeutics Center at Washington University. "Our research seeks ways to use the virus like a nanoparticle and capitalize on all the unique capacities of the virus and our ability to manipulate it."
Developing a three-pronged attack on cancer cells is in line with the NCI's pursuit of a new paradigm in cancer research. Known as theragnostics, the concept is to combine therapy and diagnostics into one targeted attack on a specific cancer.
"We would like to understand the patient's biology and direct therapy on that basis," Curiel says. "And ideally, such a personalized treatment agent should include everything you would want it to do — it would be targeted specifically to the cancer and avoid healthy cells, it would deliver therapeutic drugs, and it would have a method to image the tumor to monitor the outcome of therapy."
According to Curiel, there is a focus on nanoparticles in this three-part theragnostic tool. Similar in size to viruses, nanoparticles are also heavily studied for their anti-cancer possibilities. But Curiel argues that viruses have some advantages over nanoparticles. Unlike nanoparticles that serve only as passive carriers, viruses have DNA, which offers another layer of cancer fighting or imaging potential.
"With a virus, we can alter its genes so that it expresses a protein that could be used against the cancer, or a protein that might enable us to image the tumor," Curiel says.
And like a nanoparticle, a virus can be modified to carry different molecules, drugs and metals on its surface. Previous work by Curiel and others has identified certain proteins that would target the virus to specific tissues in the body and even specific tumor types.
In addition to targeting, Curiel and his collaborators at Louisiana State University have developed a novel way to attach heavy metals to the surface of viruses so they are visible to non-invasive X-ray imaging. In a study published in PLoS ONE last year, they demonstrated the ability to use CT scans to track the location of these metal-carrying viruses in mice.
Beyond imaging, the metal-binding viruses could also carry radioactive metals that deliver radiation therapy directly to the cancer cells while sparing healthy ones.
"Within the cancer world, this idea of theragnostics is something of a holy grail," Curiel says. "It's an idea that has preceded the technology. With this grant, we hope to make inroads in developing a cancer therapeutic that accomplishes all of these targeting, treating and imaging goals."
The grant "Targeted- and Image-Based Adenovirus Cancer Therapeutic Vectors" is supported by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). Grant 1R01CA154697-01A1.
Mathis JM, Bhatia S, Khandelwal A, Kovesdi I, Lokitz SJ, Odaka Y, Takalkar AM, Terry T, Curiel DT. Genetic incorporation of human metallothionein into the adenovirus protein IX for non-invasive SPECT imaging. PLoS ONE. February 2011.
About Washington University
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.
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Julia Evangelou Strait
Senior Medical Sciences Writer
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