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Grantee Spotlight: Beatriz M. Carreno, Ph.D. - Seeking a Vaccine to Cure Melanoma

, by CRCHD staff

Beatriz Carreno, Ph.D., Washington University School of Medicine

For the past 30 years, the number of cases of melanoma/skin cancer has been on the rise. While less common among darker-complexioned people, it is often detected in those populations at advanced stages when it is more difficult to treat. Despite the advent of new treatments, metastatic melanoma remains an incurable malignancy.

At the Washington University School of Medicine, in St. Louis, MO, immunologist Beatriz M. Carreno, Ph.D., is studying the use of vaccines as a potential cure for metastatic melanoma under an NCI/CRCHD R21 Grant. Carreno is an Associate Research Professor in the Department of Pathology and Immunology.

Melanoma occurs when the skin is exposed to high amounts of ultraviolet light, causing DNA damage and genetic mutations, which in turn can lead to the growth of cancerous tumors. In stage 4, the most advanced and serious stage of melanoma, the cancer has spread to the lymph nodes and is considered incurable. Once metastasis has occurred, gp100, a protein normally found in the body, becomes overexpressed. Taking advantage of this overexpression, Carreno developed a vaccine made from gp100 and tested its effectiveness in stimulating an immune response in the body's T-Cells and, in turn, enabling the body to destroy the cancer.

In the first phase of her study, Carreno and her team administered the vaccine to seven patients newly diagnosed with stage 4 melanoma. The patients were observed for a period of 18 weeks. The results, published in the July 22, 2013 issue of the Journal of Clinical Investigation were impressive. Six of the seven treated patients developed sustained T-cell immunity to all three melanoma gp100 antigen-derived peptides that Carreno inserted in the vaccine. One patient had a complete remission of his cancer (longer than four years). Two of the patients had a partial response. The next step will be to treat melanoma using gp100 in phase 3 patients to determine whether administering the vaccine at an earlier stage in the disease enables the treatment to be even more successful.

"My research centers on questions related to the generation and modulation of human T-cell responses and how these mechanisms can be harnessed to develop immune-based therapies for cancer," Carreno said. In the next stage of her research, Carreno will be working on building a vaccine using individual patients' unique genomic material and genetic mutations to test whether "personalized" vaccines can cause the immune system to attack the tumor. It takes between four and eight hours for Carreno to prepare the cell lines and six days to formulate the vaccine.

The field of immunology has expanded exponentially since Carreno started her career in science more than 30 years ago. "We are moving at a much faster pace than ever before," Carreno said. "In the 1980s, our understanding of cancer and cell biology was still in an immense black hole, whereas now, technology has advanced to the point where we have tools that can actually visualize cells and monitor individual immune responses."

Carreno, who hails from Caracas, Venezuela, describes the profound difference between biomedical research in her native country and the U.S. "In Venezuela, there is no research infrastructure and resources are very limited," she says. "My journey to America opened my eyes to science, with chemical compounds and technologies that I would never have been able to use in Venezuela because they are too costly and difficult to obtain."

According to Carreno, her greatest opportunities to expand her knowledge and career came only after she was awarded federal funding by NCI/CRCHD. "The R21 grant that I obtained allowed me to not only test my hypothesis that the immune system can be harvested as a treatment to destroy cancerous tumors, it also allowed the discipline of immunology to expand," she said. "Federal grants like these are extremely important and I hope NIH continues to support this kind of research."

Carreno says she chose to conduct her research at Washington University because she would have the opportunity to work with physician-scientists who could translate her basic lab research into clinical applications. "It's very satisfying to see basic lab research making a difference in people."

Carreno received her licensure in biology in 1981 from the Universidad Simón Bolívar, in Caracas. She went on to earn her Ph.D. in microbiology in 1989 from Georgetown University's School of Medicine in Washington, DC. Carreno has authored more than 45 scientific articles, written more than 10 reviews and book chapters, and holds 14 U.S. patents in immunology.

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