Alessandra Franco, MD, PhD
UC San Diego researcher Franco pioneers the concept of peptide-based vaccines to induce immune regulation by expanding natural regulatory T cells
October 17, 2016 | Patti Wieser
In 2010, Alessandra Franco, MD, PhD, received a small pilot project grant from the newly established Clinical and Translational Research Institute (CTRI) to study how natural regulatory T cells (nTregs) respond following standard treatment in Kawasaki disease (KD). Her project focused on characterizing T cell lineages in KD, which causes acute inflammation of the coronary arteries in young children, and is generally treated with intravenous immunoglobulin (IVIG). Natural regulatory T cells modulate immunity and regulate inflammatory conditions.
Results generated from her study led to a U.S. patent award in 2015 for the discovery of peptide compositions to expand nTregs that recognize a specific region of immunoglobulins. This is a novel process for IVIG function and appears to be critical to resolve KD. Franco’s discovery centers on identifying certain peptides to expand nTregs with implication for a wide range of vascular inflammatory conditions and autoimmune diseases. Peptides are small sequences of proteins; Franco discovered the immunodominant peptides derived from the Fc of immunoglobulin.
“The concept of using peptides for immune regulation is important,” said Franco, an associate professor at UC San Diego School of Medicine, Department of Pediatrics in the Division of Allergy, Immunology and Rheumatology. The peptide compositions could provide immunotherapies to promote the expansion of natural regulatory T cells to establish, or re-establish, vascular stability via immune regulation, as well as treat patients with rheumatoid arthritis, other autoimmune conditions and prevent miscarriages in autoimmune women by restoring mother-fetus tolerance.
Franco is a physician scientist, running a human T cell recognition laboratory in the Basic Science building and working closely with clinical colleagues, in particular Jane Burns, MD, and Adriana Tremoulet, MD, fellow experts in KD research. Franco came to San Diego in 1991, recruited to conduct research in T cell biology and immunotherapy, and worked at the Scripps Research Institute and La Jolla Institute for Allergy and Immunology before joining UC San Diego. Her career began “at the bedside” as a physician in Italy, where she received an MD, with a specialization in internal medicine, and a PhD in immunology from the University of Rome “La Sapienza.”
“I’m trained as an internal medicine doctor. In Rome, I was on the faculty in internal medicine and did clinical trials and developed the current vaccine for hepatitis B (HBV),” Franco said. Her interest in finding answers to some of the most complex problems in immunology brought her to “the bench,” where she studies the basic science of inflammatory disease development, treatment and prevention. Her expertise lends itself well to a niche that combines pediatric immunology and basic research. “I am here to serve human health as an academic investigator,” said Franco.
Franco is also a faculty member of the MD/PhD program at the School of Medicine, has been awarded multiple research grants, and is the author or co-author of over 60 publications in professional journals.
Her CTRI pilot project focused on understanding how regulatory T cells are primed, stimulated and expanded for KD. The core of her patent is that the expansion of regulatory T cells correlates with a favorable prognosis. “I am very grateful for the support from the CTRI,” Franco said. “We learned how to characterize immune cells in children with KD and we proved that immune monitoring is an essential secondary endpoint in clinical trials with agents that manipulate the immune system.”
On the heels of the CTRI grant, she received an R01 grant from the NIH to study immune cells in KD more fully. Through this research, Franco and her colleagues developed the concept that immune regulation is what actually downsizes the disease.
The patent takes the research to the next step in treatment and prevention. IVIG therapy generates a specific population of natural Tregs that recognize immunoglobulin G, a type of antibody, suggesting that natural Tregs play a role in controlling vascular regulation. The patented peptide compositions would generate natural Tregs that can suppress pro-inflammatory T cells and pro-inflammatory T cell responses. The discovery, she said, is the result of many years of collaborative work “centering on monitoring regulatory T-cells before and after treatment with IVIG or IVIG plus infliximab to study the role of immune regulation in modulating the immunopathology in KD.” Infliximab is an antibody medication to reduce inflammation.
Franco, who is interested in pioneering a personalized approach using vaccinations to boost immune regulation, is excited about what’s next.
“The patent identifies peptides and paves the avenue for phase I clinical trials,” Franco said. “My dream is to extend these findings to apply to a cluster of diseases when immune regulation is relevant bypassing the idea that immune suppression is the only avenue to treat inflammatory conditions.”