{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:04:33Z","timestamp":1760148273226,"version":"build-2065373602"},"reference-count":26,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Hubei Province","award":["2022CFB029","82100193"],"award-info":[{"award-number":["2022CFB029","82100193"]}]},{"name":"National Natural Science Foundation of China","award":["2022CFB029","82100193"],"award-info":[{"award-number":["2022CFB029","82100193"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy derived from T cells. Numerous CAR T therapies have been successfully applied to treat hematologic malignancies in the clinic. Nevertheless, there remain several challenges to the extensive application of CAR T cell therapy in T cell malignancies, especially in T-ALL. The main reason for CAR T therapy limitations is that T-ALL cells and normal T cells share antigens, which improves the difficulty of sorting pure T cells, resulting in product contamination, and would lead to CAR T cell fratricide. Thus, we considered creating a CAR on T-ALL tumor cells (CAR T-ALL) to prevent fratricide and eliminate tumor cells. We found that T-ALL cells transduced with CAR would actually commit fratricide. However, CAR T-ALL could kill only tumor cells on T-ALL cell lines, and other types of tumor cells had no killing function after being transferred with CAR. Furthermore, we created CD99 CAR with expression controlled by the Tet-On system on Jurkat cells, which could avoid the fratricide of CAR T-ALL during proliferation, ensuring the controllability of the killing time and effect. Jurkat transduced with a CAR-targeting antigen, which was expressed on other cancer cells, could kill other cancer cell lines, demonstrating that T-ALL cells could be used as tool cells for cancer therapy. Our study supplied a new feasible treatment regimen for cancer treatment in the clinic.<\/jats:p>","DOI":"10.3390\/vaccines11040854","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T03:14:09Z","timestamp":1681701249000},"page":"854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["T-ALL Cells as Tool Cells for CAR T Therapy"],"prefix":"10.3390","volume":"11","author":[{"given":"Anqi","family":"Ren","sequence":"first","affiliation":[{"name":"Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan 430081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan 430081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4232-835X","authenticated-orcid":false,"given":"Haichuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan 430081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3324\/haematol.2008.004150","article-title":"T-cell acute lymphoblastic leukemia","volume":"94","author":"Chiaretti","year":"2009","journal-title":"Haematologica"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1182\/asheducation-2016.1.580","article-title":"T-cell acute lymphoblastic leukemia","volume":"2016","author":"Raetz","year":"2016","journal-title":"Hematology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/S0140-6736(19)33018-1","article-title":"Acute lymphoblastic leukaemia","volume":"395","author":"Malard","year":"2020","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma","volume":"377","author":"Neelapu","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1200\/JCO.2014.56.2025","article-title":"Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-Cell Malignancies Can Be Effectively Treated With Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor","volume":"33","author":"Kochenderfer","year":"2014","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Titov, A., Kaminskiy, Y., Ganeeva, I., Zmievskaya, E., Valiullina, A., Rakhmatullina, A., Petukhov, A., Miftakhova, R., Rizvanov, A., and Bulatov, E. (2022). Knowns and Unknowns about CAR-T Cell Dysfunction. Cancers, 14.","DOI":"10.3390\/cancers14041078"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s13045-019-0801-y","article-title":"Targeting T cell malignancies using CAR-based immunotherapy: Challenges and potential solutions","volume":"12","author":"Fleischer","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1038\/s41375-018-0285-8","article-title":"CAR T-cells for T-cell malignancies: Challenges in distinguishing between therapeutic, normal, and neoplastic T-cells","volume":"32","author":"Alcantara","year":"2018","journal-title":"Leukemia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/sj.leu.2403303","article-title":"CD99 expression in T-lineage ALL: Implications for flow cytometric detection of minimal residual disease","volume":"18","author":"Dworzak","year":"2004","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13045-021-01178-z","article-title":"CAR T cells targeting CD99 as an approach to eradicate T-cell acute lymphoblastic leukemia without normal blood cells toxicity","volume":"14","author":"Shi","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"517","DOI":"10.4049\/jimmunol.152.2.517","article-title":"Expression and function of CD7 molecule on human natural killer cells","volume":"152","author":"Rabinowich","year":"1994","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1182\/bloodadvances.2017009928","article-title":"Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies","volume":"1","author":"Png","year":"2017","journal-title":"Blood Adv."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Manara, M.C., Pasello, M., and Scotlandi, K. (2018). CD99: A Cell Surface Protein with an Oncojanus Role in Tumors. Genes, 9.","DOI":"10.3390\/genes9030159"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eaaj2025","DOI":"10.1126\/scitranslmed.aaj2025","article-title":"CD99 is a therapeutic target on disease stem cells in myeloid malignancies","volume":"9","author":"Chung","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_15","first-page":"167","article-title":"TDT (\u2212), KIT (+), CD34 (+), CD99 (+) precursor T lymphoblastic leukemia\/lymphoma","volume":"5","author":"Terada","year":"2012","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1046\/j.1365-2559.2001.01309.x","article-title":"CD99\/MIC-2 surface protein expression in breast carcinomas","volume":"39","author":"Milanezi","year":"2001","journal-title":"Histopathology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1172\/JCI36667","article-title":"CD99 inhibits neural differentiation of human Ewing sarcoma cells and thereby contributes to oncogenesis","volume":"120","author":"Rocchi","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"156","DOI":"10.2174\/1566523216666160524144041","article-title":"Tet-On Systems For Doxycycline-inducible Gene Expression","volume":"16","author":"Das","year":"2016","journal-title":"Curr. Gene Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1053\/j.seminhematol.2020.11.004","article-title":"The challenge to further improvements in survival of patients with T-ALL: Current treatments and new insights from disease pathogenesis","volume":"57","year":"2020","journal-title":"Semin. Hematol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1111\/jcmm.12810","article-title":"CD19-CAR engineered NK-92 cells are sufficient to overcome NK cell resistance in B-cell malignancies","volume":"20","author":"Romanski","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref_21","first-page":"1083","article-title":"First-in-man clinical trial of CAR NK-92 cells: Safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia","volume":"8","author":"Tang","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.jcyt.2020.06.003","article-title":"Irradiated chimeric antigen receptor engineered NK-92MI cells show effective cytotoxicity against CD19+ malignancy in a mouse model","volume":"22","author":"Liu","year":"2020","journal-title":"Cytotherapy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.omto.2021.10.001","article-title":"The emerging role of off-the-shelf engineered natural killer cells in targeted cancer immunotherapy","volume":"23","author":"Fabian","year":"2021","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s13045-020-00998-9","article-title":"Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy","volume":"13","author":"Yilmaz","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41408-021-00508-1","article-title":"AAV-mediated in vivo CAR gene therapy for targeting human T-cell leukemia","volume":"11","author":"Nawaz","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/s41592-019-0329-7","article-title":"One-step generation of modular CAR-T cells with AAV\u2013Cpf1","volume":"16","author":"Dai","year":"2019","journal-title":"Nat. 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