Bispecific antibodies targeting peptide–HLA complexes for HIV

Bispecific TCR-mimicking antibodies targeting HIV-1 peptide–HLA class I complexes could help treat HIV by killing infected cells, clearing the HIV-1 latent reservoir. Mass spectrometry-based screening of HIV-1 peptides presented on HLA-A 0201 by infected CD4⁺ T cells from healthy donors was followed by screening of a phage display library for single-chain variable fragments specific for the identified peptide–HLA complexes, which were then incorporated into single-chain bispecific antibodies that also targeted CD3 to recruit T cells.

In co-cultures of primary CD4⁺ T cells infected with an HIV-1 reporter virus and autologous CD8⁺ T cells, bispecific antibodies targeting CD3 and a 9-mer peptide in complex with HLA-A 0201 decreased viable CD4⁺ cell counts compared with an isotype control, and resulted in 72% suppression of viral infection. ...