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A Universal CAR-NK Cell Targeting Various Epitopes of HIV‑1 gp160
journal contribution
posted on 2020-07-28, 20:43 authored by Rebecca
M. Lim, Liang Rong, Anjie Zhen, Jianming XieEngineering
T cells and natural killer (NK) cells with anti-HIV
chimeric antigen receptors (CAR) has emerged as a promising strategy
to eradicate HIV-infected cells. However, current anti-HIV CARs are
limited by targeting a single epitope of the HIV envelope glycoprotein
gp160, which cannot counter the enormous diversity and mutability
of viruses. Here, we report the development of a universal CAR-NK
cell, which recognizes 2,4-dinitrophenyl (DNP) and can subsequently
be redirected to target various epitopes of gp160 using DNP-conjugated
antibodies as adaptor molecules. We show that this CAR-NK cell can
recognize and kill mimic HIV-infected cell lines expressing subtypes
B and C gp160. We additionally find that anti-gp160 antibodies targeting
membrane-distal epitopes (including V1/V2, V3, and CD4bs) are more
likely to activate universal CAR-NK cells against gp160+ target cells, compared with those targeting membrane-proximal epitopes
located in the gp41 MPER. Finally, we confirm that HIV-infected primary
human CD4+ T cells can be effectively killed using the
same approach. Given that numerous anti-gp160 antibodies with different
antigen specificities are readily available, this modular universal
CAR-NK cell platform can potentially overcome HIV diversity, thus
providing a promising strategy to eradicate HIV-infected cells.