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Researchers Receive $3 million to Design Cancer-Killing Viruses

Julia Evangelou Strait

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. Ilustration courtesy of Igor Dmitriev, PhD

May 22, 2012 – Researchers at Washington University School of Medicine and the Siteman Cancer Center 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 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.

David T. Curiel, MD, PhD, Distinguished Professor of Radiation Oncology

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 noninvasive 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.