Value Proposition
· Superior target stability: Targets conserved HIV structural protein-derived peptide:MHC complexes that are highly expressed and stable, unlike rapidly-internalizing variable Env proteins used by current bispecifics
· Comprehensive MHC coverage: First platform addressing HIV peptides across MHC-I, MHC-II, and HLA-E pathways, enabling detection across all infected cell types and antigen processing mechanisms
· Technical breakthrough: Overcomes historical challenge of generating peptide:MHC-specific antibodies through innovative phage-display, avoiding cross-reactivity with uninfected cells
· Dual-purpose platform: Functions as both research tool for screening latency-reversing agents and therapeutic component addressing the critical "kill" phase gap in shock-and-kill HIV cure strategies
· Broad viral coverage: Targets structurally conserved HIV proteins rather than highly variable envelope sequences, providing superior viral strain coverage and durability
Unmet Need
HIV affects over 37 million people worldwide who require lifelong antiretroviral therapy due to persistent latent viral reservoirs in long-lived memory CD4+ T cells with a 44-month half-life that can stochastically reactivate and cause viral rebound. While "shock-and-kill" strategies using latency-reversing agents can reactivate dormant HIV, current approaches lack effective "kill" mechanisms, and existing bispecific antibodies targeting HIV envelope proteins suffer from rapid target internalization, high sequence variability, and low expression levels on infected cells. Therefore, there is a critical need for stable, broadly-reactive targeting mechanisms that can effectively eliminate reactivated latently-infected cells and serve as research tools to optimize latency reversal strategies for achieving HIV functional cure.
Technology Description
Researchers at Johns Hopkins have developed a bispecific antibody platform that targets conserved HIV structural protein-derived peptide:MHC complexes rather than envelope proteins, addressing fundamental limitations of current approaches. The technology utilizes phage-display methodology to generate antibodies with dual specificity for CD3 epsilon on T cells and HIV peptide:MHC interfaces across all three presentation pathways (MHC-I, MHC-II, and HLA-E), ensuring specificity for infected cells while avoiding cross-reactivity with uninfected MHC-expressing cells. The platform serves dual purposes as both a research tool for screening cure strategies and as a therapeutic agent for shock-and-kill regimens targeting the persistent latent reservoir.
Stage of Development
As of 10/1/2025, proof-of-concept completed with four functional bispecific reagents (two MHC-I, two MHC-II) successfully generated, purified, and characterized; HLA-E constructs in development.
Data Availability
n/a
Publication
- Sengupta, Srona, et al. "TCR-mimic bispecific antibodies to target the HIV-1 reservoir." Proceedings of the National Academy of Sciences 119.15 (2022): e2123406119. - TCR-mimic bispecific antibodies to target the HIV-1 reservoir - PubMed
- WO 2024/210907
