A 杏吧视频 researcher has been awarded more than $3 million in federal and foundation grants to turn common plant viruses into cancer sleuths and search-and-destroy emissaries.
Nicole Steinmetz, an assistant professor of biomedical engineering, will customize tobacco mosaic virus to distinguish between indolent and aggressive prostate cancers, and potato virus X to deliver a pair of treatments inside triple-negative breast cancer tumors.
The National Institutes of Health鈥檚 National Institute of Biomedical Imaging and Bioengineering (NBIB) and National Cancer Institute (NCI), and the American Cancer Society are providing the funding.
Plant virus shells have natural advantages
The tubular shape of the tobacco mosaic virus shell helps it evade the body's immune system; the flexible filaments of the potato virus X shell allow it to slip inside a tumor.
Image by Andrzej Pitek. The contrast agent will assemble inside hollowed-out protein shells of tobacco mosaic virus. The lab will customize the outside surface chemistry to seek and link to CD151 or EGFL7. Injected into the bloodstream, the elongated shape of the virus shells allow them to evade the body鈥檚 immune system and, by tumbling along the edges of the blood flow, more easily come in contact with and attach to the targets. If an MRI shows CD151 or EGFL7 is present, the prostate cancer is considered aggressive and would require monitoring and treatment. If not found, no treatment is needed. Because the contrast agent is packaged inside a protein, the researchers believe the body will recognize it as protein and quickly remove it from circulation, limiting tissue exposure to toxic gadolinium. The work builds on long-term collaboration between Steinmetz and Lewis, who have developed several virus-based sensors targeting molecular zip codes 鈥攗nique receptors in blood vessels and cancer cells of prostate tumors. Other collaborators include Xin Yu, professor of biomedical engineering at 杏吧视频 and MRI physicist on the project. Sanjay Gupta, professor of urology, and James M. Anderson, professor of pathology, at the 杏吧视频 School of Medicine, will assess the safety and potential toxicity of the CD151 package.
Nicole Steinmetz, an assistant professor of biomedical engineering, will customize tobacco mosaic virus to distinguish between indolent and aggressive prostate cancers, and potato virus X to deliver a pair of treatments inside triple-negative breast cancer tumors.
The National Institutes of Health鈥檚 National Institute of Biomedical Imaging and Bioengineering (NBIB) and National Cancer Institute (NCI), and the American Cancer Society are providing the funding.
Prognostics
Steinmetz will target two potential biomarkers of aggressive prostate cancers. 鈥淭he overall problem is, as men age, they are at increased risk for prostate tumor development,鈥 Steinmetz said. 鈥淭hey may not have to be treated if the tumor is benign, but the current PSA (prostate-specific antigen) test鈥攁 blood test鈥攊s poor at telling slow-growing from aggressive cancers.鈥 Her lab has already developed a self-assembling contrast agent to be used in magnetic resonance imaging (MRI) scans. The new agent includes a large payload of chelated gadolinium that has the potential to increase the visibility of molecular targets 10,000 times over current agents. With a $2 million grant from the NCI, Steinmetz鈥檚 lab will focus on detecting and monitoring the cell membrane protein tetraspanin CD151 over the next five years. Co-investigator John Lewis, associate professor of oncology at the University of Alberta, found that patients with increased levels of the 鈥渋ntegrin-free鈥 CD151 in their prostates had significantly increased risk for metastasis鈥攖he most deadly aspect of prostate cancer. Using a $275,000 grant from the NBIB, Steinmetz will target epidermal growth-factor like domain 7 (EGFL7), a protein coding gene. EGFL7 is expressed in the lining of prostate blood vessels that are actively growing, which is the case in aggressive prostate cancers. Plant virus shells have natural advantagesThe tubular shape of the tobacco mosaic virus shell helps it evade the body's immune system; the flexible filaments of the potato virus X shell allow it to slip inside a tumor.
Image by Andrzej Pitek. The contrast agent will assemble inside hollowed-out protein shells of tobacco mosaic virus. The lab will customize the outside surface chemistry to seek and link to CD151 or EGFL7. Injected into the bloodstream, the elongated shape of the virus shells allow them to evade the body鈥檚 immune system and, by tumbling along the edges of the blood flow, more easily come in contact with and attach to the targets. If an MRI shows CD151 or EGFL7 is present, the prostate cancer is considered aggressive and would require monitoring and treatment. If not found, no treatment is needed. Because the contrast agent is packaged inside a protein, the researchers believe the body will recognize it as protein and quickly remove it from circulation, limiting tissue exposure to toxic gadolinium. The work builds on long-term collaboration between Steinmetz and Lewis, who have developed several virus-based sensors targeting molecular zip codes 鈥攗nique receptors in blood vessels and cancer cells of prostate tumors. Other collaborators include Xin Yu, professor of biomedical engineering at 杏吧视频 and MRI physicist on the project. Sanjay Gupta, professor of urology, and James M. Anderson, professor of pathology, at the 杏吧视频 School of Medicine, will assess the safety and potential toxicity of the CD151 package.
