Grant supports next phase of three-pronged approach to gene therapy-based cure
NEW YORK, Nov. 6, 2018 --- amfAR, The Foundation for AIDS Research, has awarded $800,000 in new funding to researchers developing an ambitious gene therapy-based approach to curing HIV. The award launches a critical new phase in a study initiated in 2017 with $2.3 million in grants awarded to seven teams of researchers. Six of the teams will move forward with the next phase of the project.
amfAR has forged a unique collaboration among world leaders in gene therapy that began with a think tank in 2016. The amfAR-led meeting gave rise to a plan to create the first combination intervention that will simultaneously address the main barriers to a cure. In a three-pronged attack on the HIV reservoir, the researchers will employ broadly neutralizing antibodies, CAR stem cells—cells genetically reprogrammed to recognize and attack disease cells—and molecular scissors targeting the virus.
“This is an ambitious and complex project with very exciting potential,” said amfAR Chief Executive Officer Kevin Robert Frost. “It’s a carefully constructed strategy that involves some of the most talented and innovative scientists in the field. We think it holds great promise for developing the scientific basis of a cure by the end of 2020, which is the aim of our Countdown to a Cure for AIDS initiative.”
The researchers will test an approach that combines CAR stem cells that secrete broadly neutralizing antibodies, together with an enzyme (Brec1) that targets HIV DNA in the cell it has infected (while leaving other DNA intact), and long-term secretion of a broadly neutralizing antibody from the liver. The goal is to 1) induce CAR stem cells to kill reservoir cells; 2) to express two different antibodies to neutralize virions (virus that exists outside of cells) in the blood and tissues, and; 3) to use Brec1 to remove the provirus (virus that has been integrated into a cell’s DNA) from infected cells.
The investigators are: Hildegard Büning, Ph.D. (co-principal investigator, molecular biologist, Hannover Medical School, Hannover, Germany), who was recently named president of the European Society of Gene and Cell Therapy; Keith Jerome, M.D., Ph.D. (co-principal investigator, virologist, University of Washington, Seattle); Hans-Peter Kiem, M.D., Ph.D. (transplantation biologist, Fred Hutchinson Cancer Research Center, Seattle); Scott Kitchen, Ph.D. (molecular biologist, UCLA, Los Angeles); Drew Weissman, M.D., Ph.D. (Immunologist, University of Pennsylvania, Philadelphia); and Richard Wyatt, Ph.D. (immunologist, The Scripps Research Institute, La Jolla).
Timothy Brown (the "Berlin patient") remains the only person known to have been cured of HIV. Brown received a stem cell transplant from a donor with a rare genetic mutation known as CCR5-delta 32, which conferred resistance to HIV infection. Ten years later, he remains free of the virus.
“While Timothy Brown’s cure was the result of a very different gene therapy intervention, it nonetheless points to the enormous potential of gene therapy as a means of eliminating HIV,” said Dr. Rowena Johnston, amfAR Vice President and Director of Research. “We realize that delivering a gene therapy intervention to HIV-infected people around the world will be a considerable challenge. Part of the mandate of this group of researchers is to design a combination gene therapy intervention that could be effectively delivered by a single injection.”
The grant was supported in part by the Bill and Melinda Gates Foundation.
amfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and advocacy. Since 1985, amfAR has invested more than $517 million in its programs and has awarded more than 3,300 grants to research teams worldwide.