2023-amfar-research-grants-total-5-5-million

COMBINATION STRATEGY

Hildegard Büning, PhD

Co-Principal Investigator
Hannover Medical School, Germany
$1.3 million

A leading gene therapy researcher and a past president of the European Society of Gene and Cell Therapy, Dr. Büning is co-principal investigator of an amfAR-funded consortium of gene therapy scientists working to develop a complex, three-pronged attack on the HIV reservoir, the main barrier to a cure. Dr. Drew Weissman, recently honored with a Nobel Prize, is also a principal investigator on the study.

The strategy involves: antibodies capable of neutralizing a broad range of HIV subtypes (bNAbs); CAR stem cells—cells genetically reprogrammed to recognize and attack disease cells and which have been used successfully to treat certain blood cancers—and molecular scissors targeting the virus. With this grant, Dr. Büning and her collaborators will test the strategy in an animal study and determine the efficacy of each intervention, alone and in combination.

GENE THERAPY

Hans-Peter Kiem, MD, PhD

Fred Hutchinson Cancer Center, Seattle, WA
$480,000

Dr. Kiem 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.

CAR T CELLS

Martin Tolstrup, PhD

Aarhus University,
Denmark
$477,000

Though successful in some cancer treatments, genetically engineered CAR T cells have not been effective against HIV 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. Tolstrup will attempt to overcome these obstacles using CRISPR gene-editing technology and other strategies.

Dr. Claiborne will also attempt to optimize a CAR T cell approach for use against HIV by first engineering a panel of CARs targeting non-traditional portions of the HIV envelope and then testing them in a mouse model.

ANTIBODY-BASED CARRIERS

Steven de Taeye, PhD

University of Amsterdam,
The Netherlands
$150,000

2023 Mathilde Krim Fellowship in Biomedical Research

Antibodies are exquisitely fine-tuned to bind to their targets. Because of this ability to home in on targets, they could make convenient vehicles to ferry interventions—treatment or killing—to specific cells of interest. Dr. de Taeye is using antibody conjugates, in which an intervention is bound, or conjugated, to an antibody that in turn binds to specific cells. He is looking at several different antibody-based carrier approaches in his HIV cure investigation. The first is a toxin that can be delivered, via antibody, to T cells displaying specific surface signals. Another is an agent to stimulate the internal defenses of HIV-infected cells, leading to a cascade of events that results in destruction by the immune system.