{"doi":"10.1016/j.omtm.2021.09.008","title":"Novel TCR-like CAR-T cells targeting an HLA∗0201-restricted SSX2 epitope display strong activity against acute myeloid leukemia","abstract":"The synovial sarcoma X breakpoint 2 (SSX2) belongs to a multigene family of cancer-testis antigens and can be found overexpressed in multiple malignancies. Its restricted expression in immune-privileged normal tissues suggest that SSX2 may be a relevant target antigen for chimeric antigen receptor (CAR) therapy. We have developed a T cell receptor (TCR)-like antibody (Fab/3) that binds SSX2 peptide 41-49 (KASEKIFYV) in the context of HLA-A∗-0201. The sequence of Fab/3 was utilized to engineer a CAR with the CD3 zeta intra-cellular domain along with either a CD28 or 4-1BB costimulatory endodomain. Human T cells from HLA-A2+ donors were transduced to mediate anti-tumor activity against acute myeloid leukemia (AML) tumor cells. Upon challenge with HLA-A2+/SSX2+ AML tumor cells, CAR-expressing T cells released interferon-γ and eliminated the tumor cells in a long-term co-culture assay. Using the HLA-A2+ T2 cell line, we demonstrated a strong specificity of the single-chain variable fragment (scFv) for SSX2 p41-49 and the closely related SSX3 p41-49, with no response against the others SSX-homologous peptides or unrelated homologous peptides. Since SSX3 has not been observed in tumor cells and expression cannot be induced by pharmacological intervention, SSX241-49 represents an attractive target for CAR-based cellular therapy to treat multiple types of cancer.","journal":"Molecular Therapy — Methods & Clinical Development","year":2021,"id":179752,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":727514,"name":"Stacey Van Pelt","orcid":"0000-0002-0902-9518","position":1,"is_corresponding":false},{"id":666564,"name":"Keri Toner","orcid":"0000-0002-9324-7314","position":2,"is_corresponding":false},{"id":727515,"name":"Preethi B. Balakrishnan","orcid":"0000-0001-5576-7530","position":3,"is_corresponding":false},{"id":723019,"name":"Hema Dave","orcid":"0000-0001-5530-0201","position":4,"is_corresponding":false},{"id":263322,"name":"Catherine M. Bollard","orcid":"0000-0001-5140-9090","position":5,"is_corresponding":false},{"id":727516,"name":"Eric Yvon","orcid":"0000-0003-3822-6710","position":6,"is_corresponding":false},{"id":646978,"name":"Scott Raskin","orcid":null,"position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T23:47:48.974996Z","pmid":"34729377","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":[]}