Long-Term Control of HIV byCCR5Delta32/Delta32 Stem-Cell Transplantation

Abstract

Infection with the human immunodeficiency virus type 1 (HIV-1) requires the presence of a CD4 receptor and a chemokine receptor, principally chemokine receptor 5 (CCR5). Homozygosity for a 32-bp deletion in the CCR5 allele provides resistance against HIV-1 acquisition. We transplanted stem cells from a donor who was homozygous for CCR5 delta32 in a patient with acute myeloid leukemia and HIV-1 infection. The patient remained without viral rebound 20 months after transplantation and discontinuation of antiretroviral therapy. This outcome demonstrates the critical role CCR5 plays in maintaining HIV-1 infection.

Engineering HIV-Resistant, Anti-HIV Chimeric Antigen Receptor T Cells

“…36,37 Individuals with an allelic variant that is not functional (CCR5D32) are protected from CCR5-tropic HIV infection. 38 Hematopoietic stem cell transplant using a CCR5D32 donor led to the only known cure of HIV-1 infection, 39,40 and T cells treated with engineered nucleases that introduce mutations at the CCR5 locus are resistant to HIV, [41][42][43][44][45] accelerating ongoing efforts to develop gene editing-and cell-based therapeutic agents for HIV. 11,46 Using new gene-editing techniques, it has recently become possible to achieve high rates of homology-directed recombination (HDR) of therapeutic cassettes into targeted loci, including CCR5 in primary T cells.…”

Genome-Edited T Cell Therapies

“…Individuals homozygous for the naturally occurring CCR5 Δ32 mutation are resistant to HIV infection [108–110], making CCR5 a promising therapeutic target. Transplantation from such a donor has been reported to allow effective HIV eradication in a single case, the “Berlin patient” [111]. ZFNs have been used to knockout CCR5 expression in T cells and mediate HIV resistance in vitro with minimal off-target effects [112, 113].…”

Humanes Immunschwächevirus (HIV)

“…verbessern. Eine Elimination des HIV aus dem Körper des Infizierten durch Therapie ist bisher nicht möglich -einzige Ausnahme ist der "Berlin Patient" nach Knochenmarktransplantation von einem Spender mit homozygoter CCR5-Δ32-Deletion [181].…”