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Fc-engineered broadly neutralizing antibodies overcome cytokine-induced CD16 cleavage to drive potent ADCC against diverse HIV-1 strains.
mBio · · Journal Article
Melo, Murphy + more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
Fc-engineered broadly neutralizing antibodies with higher CD16 affinity (LPLIL and GASDALIE) significantly enhance ADCC against diverse HIV-1 subtypes despite cytokine-driven CD16 downregulation.
- Why it matters: Latent HIV-1 reservoirs are difficult to eliminate, and chronic infection can exhaust NK cells while cytokines both activate NK cells and trigger CD16 shedding that may blunt antibody killing.
- What they did: Using a primary human cell model spanning diverse HIV-1 subtypes, the study tested cytokine stimulation, ADAM17 inhibition with TAPI-1 to restore CD16, and Fc-engineered bNAbs with increased CD16 affinity.
- The result: ADAM17 inhibition did not improve ADCC, whereas LPLIL and GASDALIE increased ADCC across HIV-1 subtypes regardless of NK activation state or CD16 downregulation, supporting Fc-affinity–based “shock and kill” design.
The findingWhy it mattersWhat they didThe result
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- 3 cites