{"doi":"10.3389/fcimb.2020.00242","title":"A Trispecific Anti-HIV Chimeric Antigen Receptor Containing the CCR5 N-Terminal Region","abstract":"Anti-HIV chimeric antigen receptors (CARs) promote direct killing of infected cells, thus offering a therapeutic approach aimed at durable suppression of infection emerging from viral reservoirs. CD4-based CARs represent a favored option, since they target the essential conserved primary receptor binding site on the HIV envelope glycoprotein (Env). We have previously shown that adding a second Env-binding moiety, such as the carbohydrate recognition domain of human mannose-binding lectin (MBL) that recognizes the highly conserved oligomannose patch on gp120, increases CAR potency in an in vitro HIV suppression assay; moreover it reduces the undesired capacity for the CD4 of the CAR molecule to act as an entry receptor, thereby rendering CAR-expressing CD8+ T cells susceptible to infection. Here, we further improve the bispecific CD4-MBL CAR by adding a third targeting moiety against a distinct conserved Env determinant, i.e. a polypeptide sequence derived from the N-terminus of the HIV coreceptor CCR5. The trispecific CD4-MBL-R5Nt CAR displays enhanced in vitro anti-HIV potency compared to the CD4-MBL CAR, as well as undetectable HIV entry receptor activity. The high anti-HIV potency of the CD4-MBL-R5Nt CAR, coupled with its all-human composition and absence of immunogenic variable regions associated with antibody-based CARs, offer promise for the trispecific construct in therapeutic approaches seeking durable drug-free HIV remission.","journal":"Frontiers in Cellular and Infection Microbiology","year":2020,"id":72470,"datarank":0.7078443441718906,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.29195603583592333,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.29195603583592333,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":15,"citers_with_citation_signal":11,"citers_with_endowment":11,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"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":382446,"name":"David T. Danielson","orcid":null,"position":1,"is_corresponding":false},{"id":381834,"name":"David S. Elias","orcid":"0000-0002-4363-3057","position":2,"is_corresponding":false},{"id":382447,"name":"Virgilio Bundoc","orcid":null,"position":3,"is_corresponding":false},{"id":381835,"name":"Aaron Scanlan","orcid":"0000-0002-0465-7072","position":4,"is_corresponding":false},{"id":381836,"name":"Edward A. Berger","orcid":"0000-0001-8457-3997","position":5,"is_corresponding":false},{"id":382445,"name":"Agnes Hajduczki","orcid":null,"position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:44:45.622639Z","pmid":"32523897","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":[]}