{"doi":"10.3389/fmed.2020.588453","title":"Characterization of Donor Variability for γδ T Cell ex vivo Expansion and Development of an Allogeneic γδ T Cell Immunotherapy","abstract":"Gamma delta (γδ) T cells recently emerged as an attractive candidate for cancer immunotherapy treatments due to their inherent cytotoxicity against both hematological and solid tumors. Moreover, γδ T cells provide a platform for the development of allogeneic cell therapies, as they can recognize antigens independent of MHC recognition and without the requirement for a chimeric antigen receptor. However, γδ T cell adoptive cell therapy depends on ex vivo expansion to manufacture sufficient cell product numbers, which remains challenging and limited by inter-donor variability. In the current study, we characterize the differences in expansion of γδ T cells from various donors that expand (EX) and donors that fail to expand, i.e. non-expanders (NE). Further, we demonstrate that IL-21 can be used to increase the expansion potential of NE. In order to reduce the risk of graft versus host disease (GVHD) induced by an allogeneic T cell product, αβ T cell depletions must be considered due to the potential for HLA mismatch. Typically, αβ T cell depletions are performed at the end of expansion, prior to infusion. We show that γδ T cell cultures can be successfully αβ depleted on day 6 of expansion, providing a better environment for the γδ T cells to expand, and that the αβ T cell population remains below clinically acceptable standards for T cell-depleted allogeneic stem cell products. Finally, we assess the potential for a mixed donor γδ T cell therapy and characterize the effects of cryopreservation on γδ T cells. Collectively, these studies support the development of an improved allogeneic γδ T cell product and suggest the possibility of using mixed donor γδ T cell immunotherapies.","journal":"Frontiers in Medicine","year":2020,"id":94499,"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":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"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":471008,"name":"Jaquelyn T. Zoine","orcid":"0000-0001-7914-4610","position":1,"is_corresponding":false},{"id":472178,"name":"Jamie Y. Story","orcid":null,"position":2,"is_corresponding":false},{"id":472179,"name":"Swetha N. Garimalla","orcid":null,"position":3,"is_corresponding":false},{"id":24173,"name":"Greg Gibson","orcid":"0000-0002-5352-5877","position":4,"is_corresponding":false},{"id":472180,"name":"Aaron Rae","orcid":null,"position":5,"is_corresponding":false},{"id":472181,"name":"Erich Williams","orcid":null,"position":6,"is_corresponding":false},{"id":471009,"name":"Lisa M. Bixby","orcid":"0000-0002-4036-9262","position":7,"is_corresponding":false},{"id":471010,"name":"David R. Archer","orcid":"0000-0002-9185-0865","position":8,"is_corresponding":false},{"id":380170,"name":"Christopher B. Doering","orcid":"0000-0002-5662-0060","position":9,"is_corresponding":false},{"id":380171,"name":"H. Trent Spencer","orcid":"0000-0001-8062-2202","position":10,"is_corresponding":false},{"id":471007,"name":"Rebecca E. Burnham","orcid":"0000-0001-7904-6455","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T22:33:00.770265Z","pmid":"33282892","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":[]}