amfAR Grants Advance Gene Therapy Approaches to Curing HIV
amfAR has awarded new grants totaling $2.4 million to research teams in the U.S. and Europe developing and testing a range of innovative gene therapy approaches to curing HIV.
“Gene therapy is a tremendously exciting field with enormous, but as yet untapped, potential against HIV,” said Kevin Robert Frost, amfAR’s chief executive officer. “This round of grants will advance projects being undertaken by some of the world’s most eminent gene therapy researchers, who have the skills and now, we hope, the resources to make real progress toward an accessible cure for people living with HIV.”
Read a commentary on gene therapy and curing HIV by Dr. Jeffrey Laurence, amfAR’s senior scientific consultant, by clicking here.
A leading gene therapy researcher at Hannover Medical School, Germany, and a past president of the European Society of Gene and Cell Therapy, Dr. Hildegard Büning was co-principal investigator of a consortium of gene therapy scientists that previously received funding from amfAR to develop a complex, three-pronged attack on the HIV reservoir, the main barrier to a cure.
The three components of the strategy have now been developed and fine-tuned and will be tested in an animal study for which Dr. Büning has been awarded an amfAR grant of $1.3 million. The strategy involves: antibodies capable of neutralizing a broad range of HIV subtypes; CAR stem cells—cells genetically reprogrammed to recognize and attack disease cells; and molecular scissors targeting the virus. At the end of this proof-of-concept study, the researchers will determine the efficacy of each intervention, alone and in combination.
In a recent amfAR interview, IAS President Sharon Lewin advocates for gene therapy research in the quest to cure HIV.
A second grant of $480,000 was awarded to Dr. Hans-Peter Kiem of Fred Hutchinson Cancer Center in Seattle for a project that seeks to develop a “portable gene therapy treatment” within a patient’s body as part of an HIV cure intervention. The five cases of HIV cure documented to date have been achieved by a stem cell transplant introducing donor cells with the CCR5-delta32 mutation, which renders them effectively immune to HIV infection. In an effort to avoid this complex and high-risk procedure, and to design a cure that could be applicable to low-resource countries, Dr. Kiem will test engineered virus-like particles that can deliver gene-editing enzymes directly to the blood, liver, brain, etc., in an animal model in an attempt to disrupt the CCR5 receptor in blood-forming stem cells.
A world-renowned pioneer in stem-cell and gene therapy and in the development of new gene-editing technologies, Dr. Kiem was part of the research consortium co-led by Dr. Büning (see above).
Genetically engineered CAR T cells have been remarkably successful in treating certain types of cancer, but their potential against HIV remains unfulfilled for several reasons: CAR T cells are themselves vulnerable to HIV infection, and, even when they remain uninfected, they cannot achieve broad enough coverage or persist long enough to be effective. Dr. Martin Tolstrup of Aarhus University in Denmark was awarded a grant of $477,000 to attempt to overcome these obstacles using CRISPR gene-editing technology and other strategies.
Dr. Daniel Claiborne of The Wistar Institute in Philadelphia will also attempt to optimize a CAR T cell approach for use against HIV with a grant of $120,000. Dr. Claiborne will engineer a panel of CARs targeting non-traditional portions of the HIV envelope and test them in a mouse model.