ArticleThe Journal of clinical investigation2015
Dual-Affinity Re-Targeting proteins direct T cell-mediated cytolysis of latently HIV-infected cells.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 131 citations in OpenAlex.
- Boosting with AIDSVAX B/E Enhances Env Constant Region 1 and 2 Antibody-Dependent Cellular Cytotoxicity Breadth and Potency.Journal of virology · 2020Trial
- In-vivo administration of histone deacetylase inhibitors does not impair natural killer cell function in HIV+ individuals.AIDS (London, England) · 2019Trial
- Review
- Review
- A TCR-mimic bispecific antibody reduces HIV-1 provirus and delays viral rebound in HLA-matched humanized mice.bioRxiv : the preprint server for biology · 2025Article
- Engineering of CD8mBio · 2025Article
- NK cell depletion in bispecific antibody therapy is associated with lack of HIV control after ART interruption.Communications biology · 2025Article
- Adeno-Associated Virus (AAV)-Delivered Exosomal TAT and BiTE Molecule CD4-αCD3 Facilitate the Elimination of CD4 T Cells Harboring Latent HIV-1.Microorganisms · 2024Article
- Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases.Cellular & molecular immunology · 2024Review
- Bispecific antibodies promote natural killer cell-mediated elimination of HIV-1 reservoir cells.Nature immunology · 2024Article
- Highly Sensitive Analysis of Cervical Mucosal HIV-1 Infection Using Reporter Viruses Expressing Secreted Nanoluciferase.Methods in molecular biology (Clifton, N.J.) · 2024Article
- A Critical Analysis of the FDA's Omics-Driven Pharmacodynamic Biomarkers to Establish Biosimilarity.Pharmaceuticals (Basel, Switzerland) · 2023Review
- NK cell subsets and dysfunction during viral infection: a new avenue for therapeutics?Frontiers in immunology · 2023Review
- Monoclonal Antibodies as Long-Acting Products: What Are We Learning From Human Immunodeficiency Virus (HIV) and Coronavirus Disease 2019 (COVID-19)?Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Anti-viral efficacy of a next-generation CD4-binding site bNAb in SHIV-infected animals in the absence of anti-drug antibody responses.iScience · 2022Article
- Bispecific antibody-derived molecules to target persistent HIV infection.Journal of virus eradication · 2022Article
- Engaging innate immunity in HIV-1 cure strategies.Nature reviews. Immunology · 2022Review
- TCR-mimic bispecific antibodies to target the HIV-1 reservoir.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Detection of the HIV-1 Accessory Proteins Nef and Vpu by Flow Cytometry Represents a New Tool to Study Their Functional Interplay within a Single Infected CD4Journal of virology · 2022Article
- Activation of distinct antiviral T-cell immunity: A comparison of bi- and trispecific T-cell engager antibodies with a chimeric antigen receptor targeting HBV envelope proteins.Frontiers in immunology · 2022Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 4 institutions in 1 country.
Funding
Abstract
Enhancement of HIV-specific immunity is likely required to eliminate latent HIV infection. Here, we have developed an immunotherapeutic modality aimed to improve T cell-mediated clearance of HIV-1-infected cells. Specifically, we employed Dual-Affinity Re-Targeting (DART) proteins, which are bispecific, antibody-based molecules that can bind 2 distinct cell-surface molecules simultaneously. We designed DARTs with a monovalent HIV-1 envelope-binding (Env-binding) arm that was derived from broadly binding, antibody-dependent cellular cytotoxicity-mediating antibodies known to bind to HIV-infected target cells coupled to a monovalent CD3 binding arm designed to engage cytolytic effector T cells (referred to as HIVxCD3 DARTs). Thus, these DARTs redirected polyclonal T cells to specifically engage with and kill Env-expressing cells, including CD4+ T cells infected with different HIV-1 subtypes, thereby obviating the requirement for HIV-specific immunity. Using lymphocytes from patients on suppressive antiretroviral therapy (ART), we demonstrated that DARTs mediate CD8+ T cell clearance of CD4+ T cells that are superinfected with the HIV-1 strain JR-CSF or infected with autologous reservoir viruses isolated from HIV-infected-patient resting CD4+ T cells. Moreover, DARTs mediated CD8+ T cell clearance of HIV from resting CD4+ T cell cultures following induction of latent virus expression. Combined with HIV latency reversing agents, HIVxCD3 DARTs have the potential to be effective immunotherapeutic agents to clear latent HIV-1 reservoirs in HIV-infected individuals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.