{"doi":"10.1186/s12967-024-05197-5","title":"Deciphering the importance of culture pH on CD22 CAR T-cells characteristics","abstract":"BACKGROUND: Chimeric antigen receptor (CAR) T-cells have demonstrated significant efficacy in targeting hematological malignancies, and their use continues to expand. Despite substantial efforts spent on the optimization of protocols for CAR T-cell manufacturing, critical parameters of cell culture such as pH or oxygenation are rarely actively monitored during cGMP CAR T-cell generation. A comprehensive understanding of the role that these factors play in manufacturing may help in optimizing patient-specific CAR T-cell therapy with maximum benefits and minimal toxicity. METHODS: This retrospective study examined cell culture supernatants from the manufacture of CAR T-cells for 20 patients with B-cell malignancies enrolled in a phase 1/2 clinical trial of anti-CD22 CAR T-cells. MetaFLEX was used to measure supernatant pH, oxygenation, and metabolites, and a Bio-Plex assay was used to assess protein levels. Correlations were assessed between the pH of cell culture media throughout manufacturing and cell proliferation as well as clinical outcomes. Next-generation sequencing was conducted to examine gene expression profiles of the final CAR T-cell products. RESULTS: A pH level at the lower range of normal at the beginning of the manufacturing process significantly correlated with measures of T-cell expansion and metabolism. Stable or rising pH during the manufacturing process was associated with clinical response, whereas a drop in pH was associated with non-response. CONCLUSIONS: pH has potential to serve as an informative factor in predicting CAR T-cell quality and clinical outcomes. Thus, its active monitoring during manufacturing may ensure a more effective CAR T-cell product.","journal":"Journal of Translational Medicine","year":2024,"id":454420,"datarank":0.38658474681285593,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.07466851556088051,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.07466851556088051,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":6,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":912093,"name":"Alexandra Dreyzin","orcid":"0000-0003-1414-290X","position":1,"is_corresponding":false},{"id":467691,"name":"Lipei Shao","orcid":"0000-0003-3009-7096","position":2,"is_corresponding":false},{"id":1277946,"name":"P Arazo Garcés","orcid":null,"position":3,"is_corresponding":false},{"id":467690,"name":"Yihua Cai","orcid":"0000-0002-3693-9533","position":4,"is_corresponding":false},{"id":467689,"name":"Rongye Shi","orcid":"0000-0003-4298-9358","position":5,"is_corresponding":false},{"id":865240,"name":"Alejandra Pelayo","orcid":null,"position":6,"is_corresponding":false},{"id":1277947,"name":"Yong Soo Kim","orcid":null,"position":7,"is_corresponding":false},{"id":782916,"name":"Victoria C. 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