{"doi":"10.3389/fimmu.2020.00713","title":"Redirection of Cord Blood T Cells and Natural Killer Cells for Elimination of Autologous HIV-1-Infected Target Cells Using Bispecific DART® Molecules","abstract":"Mother-to-child transmission of HIV-1 remains a major global health challenge. Currently, HIV-1-infected infants require strict lifelong adherence to antiretroviral therapy to prevent replication of virus from reservoirs of infected cells, and to halt progression of disease. There is a critical need for immune interventions that can be deployed shortly after infection to eliminate HIV-1-infected cells in order to promote long-term remission of viremia, or to potentially cure pediatric HIV-1-infection. Bispecific HIV x CD3 DART® molecules able to co-engage the HIV-1 envelope protein on the surface of infected cells and CD3 on cytolytic T cells have been previously shown to eliminate HIV-1 infected cells in vitro and are candidates for passive immunotherapy to reduce the virus reservoir. However, their potential utility as therapy for infant HIV-1 infection is unclear as the ability of these novel antibody-based molecules to work in concert with cells of the infant immune system had not been assessed. Here, we use human umbilical cord blood as a model of the naïve neonatal immune system to evaluate the ability of HIV x CD3 DART molecules to recruit and redirect neonatal effector cells for elimination of autologous CD4+ T cells infected with HIV-1 encoding an envelope gene sequenced from a mother-to-child transmission event. We found that HIV x CD3 DART molecules can redirect T cells present in cord blood for elimination of HIV-infected CD4+ T cells. However, we observed reduced killing by T cells isolated from cord blood when compared to cells isolated from adult peripheral blood —likely due to the absence of the memory and effector CD8+ T cells that are most cytolytic when redirected by bispecific DART molecules. We also found that newly developed HIV x CD16 DART molecules were able to recruit CD16-expressing natural killer cells from cord blood to eliminate HIV-infected cells, and the activity of cord blood natural killer cells could be substantially increased by priming with IL-15. Our results support continued development of HIV-specific DART molecules using relevant preclinical animal models to optimize strategies for effective use of this immune therapy to reduce HIV-1 infection in pediatric populations.","journal":"Frontiers in Immunology","year":2020,"id":85908,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":439166,"name":"R. Whitney Edwards","orcid":null,"position":1,"is_corresponding":false},{"id":438387,"name":"Shalini Jha","orcid":"0000-0002-9792-2161","position":2,"is_corresponding":false},{"id":439167,"name":"Chia‐Ying K. Lam","orcid":null,"position":3,"is_corresponding":false},{"id":438388,"name":"Liqin Liu","orcid":"0000-0001-7158-6772","position":4,"is_corresponding":false},{"id":438389,"name":"Gundo Diedrich","orcid":"0000-0001-5109-0307","position":5,"is_corresponding":false},{"id":439168,"name":"Jeffrey L. Nordstrom","orcid":null,"position":6,"is_corresponding":false},{"id":439169,"name":"Tori Huffman","orcid":null,"position":7,"is_corresponding":false},{"id":439170,"name":"Joy Pickeral","orcid":null,"position":8,"is_corresponding":false},{"id":325732,"name":"Thomas N. Denny","orcid":"0000-0002-7364-8276","position":9,"is_corresponding":false},{"id":240902,"name":"Sallie R. Permar","orcid":"0000-0003-1438-4554","position":10,"is_corresponding":false},{"id":249714,"name":"Guido Ferrari","orcid":"0000-0001-7747-3349","position":11,"is_corresponding":false},{"id":344231,"name":"Justin Pollara","orcid":"0000-0003-1892-4722","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-18T21:58:16.217017Z","pmid":"32373131","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}