Nienke Visser, Macarena González-Corrales, Jimena Álvarez-Freile, Maurien G Pruis, Lena Rockstein, Harm Jan Lourens, Jan Jacob Schuringa, Tom van Meerten, Gerwin Huls, Edwin Bremer
{"title":"K12-ligand-based CAR T cell therapy for CD7-positive T cell malignancies.","authors":"Nienke Visser, Macarena González-Corrales, Jimena Álvarez-Freile, Maurien G Pruis, Lena Rockstein, Harm Jan Lourens, Jan Jacob Schuringa, Tom van Meerten, Gerwin Huls, Edwin Bremer","doi":"10.1016/j.omton.2025.200988","DOIUrl":null,"url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-based therapy is of interest for relapsed or refractory (r/r) T cell acute lymphoblastic leukemia (T-ALL) and T cell lymphomas. A prominent target antigen for this is the receptor CD7, which is expressed in ∼95% of T-ALL, ∼50% of peripheral T cell lymphomas, as well as 10% of acute myeloid leukemias. Here, we preclinically evaluated and compared CD7-targeted ligand K12-based CAR-T to an scFvCD7-based CAR-T construct. K12 CAR-T cells produced significantly higher interferon gamma (IFN-γ) after CD7 activation compared to scFv-CD7 CAR-T cells. Similarly, in a Jurkat<sup>NFAT-luc</sup> reporter cell line expressing the respective CAR, CD7-induced luminescence was significantly higher by the K12 CAR than the scFv-CD7 CAR. K12 CAR-T treatment selectively and specifically eliminated a panel of CD7-positive, but not CD7-negative, cell lines and eliminated acute-T-cell-leukemia-patient-derived and acute myeloid leukemia blasts in an effector-to-target ratio-dependent manner. Further, K12 CAR-T cells had prominent anti-leukemic activity in an intravenously (i.v.) injected Jurkat leukemia mouse model, with no detectable disease in three out of five mice treated with K12 CAR-T. Therefore, K12 CAR T cell therapy might be of use for the treatment of r/r patients with CD7-positive T cell leukemia/lymphoma and acute myeloid leukemia (AML).</p>","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"33 2","pages":"200988"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208613/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular therapy. Oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.omton.2025.200988","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/18 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Chimeric antigen receptor (CAR)-based therapy is of interest for relapsed or refractory (r/r) T cell acute lymphoblastic leukemia (T-ALL) and T cell lymphomas. A prominent target antigen for this is the receptor CD7, which is expressed in ∼95% of T-ALL, ∼50% of peripheral T cell lymphomas, as well as 10% of acute myeloid leukemias. Here, we preclinically evaluated and compared CD7-targeted ligand K12-based CAR-T to an scFvCD7-based CAR-T construct. K12 CAR-T cells produced significantly higher interferon gamma (IFN-γ) after CD7 activation compared to scFv-CD7 CAR-T cells. Similarly, in a JurkatNFAT-luc reporter cell line expressing the respective CAR, CD7-induced luminescence was significantly higher by the K12 CAR than the scFv-CD7 CAR. K12 CAR-T treatment selectively and specifically eliminated a panel of CD7-positive, but not CD7-negative, cell lines and eliminated acute-T-cell-leukemia-patient-derived and acute myeloid leukemia blasts in an effector-to-target ratio-dependent manner. Further, K12 CAR-T cells had prominent anti-leukemic activity in an intravenously (i.v.) injected Jurkat leukemia mouse model, with no detectable disease in three out of five mice treated with K12 CAR-T. Therefore, K12 CAR T cell therapy might be of use for the treatment of r/r patients with CD7-positive T cell leukemia/lymphoma and acute myeloid leukemia (AML).