{"doi":"10.1182/blood.2022016660","title":"Murine allogeneic CAR T cells integrated before or early after posttransplant cyclophosphamide exert antitumor effects","abstract":"Relapse limits the therapeutic efficacy both of chimeric antigen receptor (CAR) T cells and allogeneic hematopoietic cell transplantation (allo-HCT). Patients may undergo these therapies sequentially to prevent or treat relapsed malignancy. However, direct integration of the 2 therapies has been avoided over concerns for potential induction of graft-versus-host disease (GVHD) by allogeneic CAR T cells. We have shown in murine T-cell-replete MHC-haploidentical allo-HCT that suppressive mechanisms induced immediately after posttransplant cyclophosphamide (PTCy), given on days +3/+4, prevent GVHD induction by alloreactive T cells infused as early as day +5. Therefore, we hypothesized that allogeneic CAR T cells given in a similarly integrated manner in our murine MHC-haploidentical allo-HCT model may safely exert antitumor effects. Indeed, allogeneic anti-CD19 CAR T cells given early after (day +5) PTCy or even prior to (day 0) PTCy cleared leukemia without exacerbating the cytokine release syndrome occurring from the MHC-haploidentical allo-HCT or interfering with PTCy-mediated GVHD prevention. Meanwhile, CAR T-cell treatment on day +9 or day +14 was safe but less effective, suggesting a limited therapeutic window. CAR T cells infused before PTCy were not eliminated, but surviving CAR T cells continued to proliferate highly and expand despite PTCy. In comparison with infusion on day +5, CAR T-cell infusion on day 0 demonstrated superior clinical efficacy associated with earlier CAR T-cell expansion, higher phenotypic CAR T-cell activation, less CD4+CD25+Foxp3+ CAR T-cell recovery, and transcriptional changes suggesting increased activation of CD4+ CAR T cells and more cytotoxic CD8+ CAR T cells. This study provides mechanistic insight into PTCy's impact on graft-versus-tumor immunity and describes novel approaches to integrate CAR T cells and allo-HCT that may compensate for deficiencies of each individual approach.","journal":"Blood","year":2022,"id":282772,"datarank":0.3439477739794943,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.032031542727518826,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.032031542727518826,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":5,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":876611,"name":"Shanzay M. Khan","orcid":null,"position":1,"is_corresponding":false},{"id":875885,"name":"Natália Schneider","orcid":"0000-0003-1950-4391","position":2,"is_corresponding":false},{"id":876612,"name":"Rochelle Fletcher","orcid":null,"position":3,"is_corresponding":false},{"id":641938,"name":"Jing Bian","orcid":"0000-0001-7109-716X","position":4,"is_corresponding":false},{"id":875884,"name":"Ashley Hadjis","orcid":"0000-0002-7440-2120","position":5,"is_corresponding":false},{"id":310094,"name":"Michael Eckhaus","orcid":null,"position":6,"is_corresponding":false},{"id":477162,"name":"Suresh K. Mendu","orcid":"0000-0002-6785-0806","position":7,"is_corresponding":false},{"id":370363,"name":"Alessandra de Paula Pohl","orcid":null,"position":8,"is_corresponding":false},{"id":109204,"name":"David Venzon","orcid":"0000-0002-8990-158X","position":9,"is_corresponding":false},{"id":291439,"name":"Hyoyoung Choo‐Wosoba","orcid":"0000-0002-8756-1016","position":10,"is_corresponding":false},{"id":309017,"name":"Kazusa Ishii","orcid":"0000-0002-1915-6334","position":11,"is_corresponding":false},{"id":309021,"name":"Haiying Qin","orcid":"0000-0001-5966-8812","position":12,"is_corresponding":false},{"id":309028,"name":"Terry J. Fry","orcid":"0000-0001-8044-5226","position":13,"is_corresponding":false},{"id":261159,"name":"Maggie Cam","orcid":null,"position":14,"is_corresponding":false},{"id":564604,"name":"Christopher G. Kanakry","orcid":"0000-0002-7736-2056","position":15,"is_corresponding":false},{"id":907328,"name":"Michael T. Patterson","orcid":"0000-0002-7632-7267","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:29:19.691592Z","pmid":"36201744","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":[]}