{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T01:58:08Z","timestamp":1780970288763,"version":"3.54.1"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073404"],"award-info":[{"award-number":["82073404"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["ZYJC21003"],"award-info":[{"award-number":["ZYJC21003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["TFJC2023010006"],"award-info":[{"award-number":["TFJC2023010006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2022CJE09013"],"award-info":[{"award-number":["2022CJE09013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2023HXBH099"],"award-info":[{"award-number":["2023HXBH099"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"1\u00b73\u00b75 project for disciplines of excellence, West China Hospital, Sichuan University","award":["82073404"],"award-info":[{"award-number":["82073404"]}]},{"name":"1\u00b73\u00b75 project for disciplines of excellence, West China Hospital, Sichuan University","award":["ZYJC21003"],"award-info":[{"award-number":["ZYJC21003"]}]},{"name":"1\u00b73\u00b75 project for disciplines of excellence, West China Hospital, Sichuan University","award":["TFJC2023010006"],"award-info":[{"award-number":["TFJC2023010006"]}]},{"name":"1\u00b73\u00b75 project for disciplines of excellence, West China Hospital, Sichuan University","award":["2022CJE09013"],"award-info":[{"award-number":["2022CJE09013"]}]},{"name":"1\u00b73\u00b75 project for disciplines of excellence, West China Hospital, Sichuan University","award":["2023HXBH099"],"award-info":[{"award-number":["2023HXBH099"]}]},{"name":"Frontiers Medical Center, Tianfu Jincheng Laboratory Foundation","award":["82073404"],"award-info":[{"award-number":["82073404"]}]},{"name":"Frontiers Medical Center, Tianfu Jincheng Laboratory Foundation","award":["ZYJC21003"],"award-info":[{"award-number":["ZYJC21003"]}]},{"name":"Frontiers Medical Center, Tianfu Jincheng Laboratory Foundation","award":["TFJC2023010006"],"award-info":[{"award-number":["TFJC2023010006"]}]},{"name":"Frontiers Medical Center, Tianfu Jincheng Laboratory Foundation","award":["2022CJE09013"],"award-info":[{"award-number":["2022CJE09013"]}]},{"name":"Frontiers Medical Center, Tianfu Jincheng Laboratory Foundation","award":["2023HXBH099"],"award-info":[{"award-number":["2023HXBH099"]}]},{"name":"Major scientific and technological achievements transformation project, Ningxia Hui Autonomous Region","award":["82073404"],"award-info":[{"award-number":["82073404"]}]},{"name":"Major scientific and technological achievements transformation project, Ningxia Hui Autonomous Region","award":["ZYJC21003"],"award-info":[{"award-number":["ZYJC21003"]}]},{"name":"Major scientific and technological achievements transformation project, Ningxia Hui Autonomous Region","award":["TFJC2023010006"],"award-info":[{"award-number":["TFJC2023010006"]}]},{"name":"Major scientific and technological achievements transformation project, Ningxia Hui Autonomous Region","award":["2022CJE09013"],"award-info":[{"award-number":["2022CJE09013"]}]},{"name":"Major scientific and technological achievements transformation project, Ningxia Hui Autonomous Region","award":["2023HXBH099"],"award-info":[{"award-number":["2023HXBH099"]}]},{"name":"Post-Doctor Research Project, West China Hospital, Sichuan University","award":["82073404"],"award-info":[{"award-number":["82073404"]}]},{"name":"Post-Doctor Research Project, West China Hospital, Sichuan University","award":["ZYJC21003"],"award-info":[{"award-number":["ZYJC21003"]}]},{"name":"Post-Doctor Research Project, West China Hospital, Sichuan University","award":["TFJC2023010006"],"award-info":[{"award-number":["TFJC2023010006"]}]},{"name":"Post-Doctor Research Project, West China Hospital, Sichuan University","award":["2022CJE09013"],"award-info":[{"award-number":["2022CJE09013"]}]},{"name":"Post-Doctor Research Project, West China Hospital, Sichuan University","award":["2023HXBH099"],"award-info":[{"award-number":["2023HXBH099"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Acute T-lymphoblastic leukemia (T-ALL) is a type of leukemia that can occur in both pediatric and adult populations. Compared to acute B-cell lymphoblastic leukemia (B-ALL), patients with T-cell T-ALL have a poorer therapeutic efficacy. In this study, a novel anti-CD7 antibody\u2013drug conjugate (ADC, J87-Dxd) was successfully generated and used for T-ALL treatment. Firstly, to obtain anti-CD7 mAbs, we expressed and purified the CD7 protein extracellular domain. Utilizing hybridoma technology, we obtained three anti-CD7 mAbs (J87, G73 and A15) with a high affinity for CD7. Both the results of immunofluorescence and Biacore assay indicated that J87 (KD = 1.54 \u00d7 10\u221210 M) had the highest affinity among the three anti-CD7 mAbs. In addition, an internalization assay showed the internalization level of J87 to be higher than that of the other two mAbs. Next, we successfully generated the anti-CD7 ADC (J87-Dxd) by conjugating DXd to J87 via a cleavable maleimide-GGFG peptide linker. J87-Dxd also possessed the ability to recognize and bind CD7. Using J87-Dxd to treat T-ALL cells (Jurkat and CCRF-CEM), we observed that J87-Dxd bound to CD7 was internalized into T-ALL cells. Moreover, J87-Dxd treatment significantly induced the apoptosis of Jurkat and CCRF-CEM cells. The IC50 (half-maximal inhibitory concentration) value of J87-Dxd against CCRF-CEM obtained by CCK-8 assay was 6.3 nM. Finally, to assess the antitumor efficacy of a J87-Dxd in vivo, we established T-ALL mouse models and treated mice with J87-Dxd or J87. The results showed that on day 24 after tumor inoculation, all mice treated with J87 or PBS died, whereas the survival rate of mice treated with J87-Dxd was 80%. H&amp;E staining showed no significant organic changes in the heart, liver, spleen, lungs and kidneys of all mice. In summary, we demonstrated that the novel anti-CD7 ADC (J87-Dxd) had a potent and selective effect against CD7-expressing T-All cells both in vitro and in vivo, and could thus be expected to be further developed as a new drug for the treatment of T-ALL or other CD7-expression tumors.<\/jats:p>","DOI":"10.3390\/biom14010106","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T04:03:26Z","timestamp":1705291406000},"page":"106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["An Anti-CD7 Antibody\u2013Drug Conjugate Target Showing Potent Antitumor Activity for T-Lymphoblastic Leukemia (T-ALL)"],"prefix":"10.3390","volume":"14","author":[{"given":"Shiqi","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunhong","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Tong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1007\/s11899-018-0470-x","article-title":"CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: Transforming the Treatment of Relapsed and Refractory Disease","volume":"13","author":"Pehlivan","year":"2018","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2014073","DOI":"10.4084\/mjhid.2014.073","article-title":"Diagnosis and subclassification of acute lymphoblastic leukemia","volume":"6","author":"Chiaretti","year":"2014","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Shiraz, P., Jehangir, W., and Agrawal, V. (2021). T-Cell Acute Lymphoblastic Leukemia-Current Concepts in Molecular Biology and Management. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111621"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/bjh.17310","article-title":"Current and emerging therapeutic approaches for T-cell acute lymphoblastic leukaemia","volume":"194","author":"Pocock","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e170580","DOI":"10.1001\/jamaoncol.2017.0580","article-title":"Association of Minimal Residual Disease with Clinical Outcome in Pediatric and Adult Acute Lymphoblastic Leukemia AMeta-analysis","volume":"3","author":"Berry","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/hematology.2021000225","article-title":"Relapsed ALL: CAR T vs transplant vs novel therapies","volume":"2021","author":"Frey","year":"2021","journal-title":"Hematol.-Am. Soc. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1186\/s12935-022-02679-8","article-title":"Potential of antibody-drug conjugates (ADCs) for cancer therapy","volume":"22","author":"Marei","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kesireddy, M., Kothapalli, S.R., Gundepalli, S.G., and Asif, S. (Pharm. Med., 2023). A Review of the Current FDA-Approved Antibody-Drug Conjugates: Landmark Clinical Trials and Indications, Pharm. Med., ahead of print.","DOI":"10.1007\/s40290-023-00505-8"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3886","DOI":"10.3390\/cancers15153886","article-title":"Antibody-Drug Conjugates: A Review of Approved Drugs and Their Clinical Level of Evidence","volume":"15","author":"Gogia","year":"2023","journal-title":"Cancers"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41392-022-00947-7","article-title":"Antibody drug conjugate: The \u201cbiological missile\u201d for targeted cancer therapy","volume":"7","author":"Fu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2147\/ITT.S288546","article-title":"Targeting CD22 for the Treatment of B-Cell Malignancies","volume":"10","author":"Shah","year":"2021","journal-title":"ImmunoTargets Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s40164-020-00189-9","article-title":"Recent updates for antibody therapy for acute lymphoblastic leukemia","volume":"9","author":"Li","year":"2020","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1182\/blood-2017-01-761320","article-title":"CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies","volume":"130","author":"Srinivasan","year":"2017","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0145-2126(03)00180-2","article-title":"Prognostic relevance of immunophenotyping in 379 patients with acute myeloid leukemia","volume":"28","author":"Chang","year":"2004","journal-title":"Leuk. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41375-018-0180-3","article-title":"Coexpression profile of leukemic stem cell markers for combinatorial targeted therapy in AML","volume":"33","author":"Haubner","year":"2019","journal-title":"Leukemia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"967754","DOI":"10.3389\/fonc.2022.967754","article-title":"Chimeric antigen receptor T-cell therapy for T-ALL and AML","volume":"12","author":"Wei","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ponziani, S., Di Vittorio, G., Pitari, G., Cimini, A.M., Ardini, M., Gentile, R., Iacobelli, S., Sala, G., Capone, E., and Flavell, D.J. (2020). Antibody-Drug Conjugates: The New Frontier of Chemotherapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155510"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jim.2008.11.004","article-title":"Anti-peptide antibody screening: Selection of high affinity monoclonal reagents by a refined surface plasmon resonance technique","volume":"341","author":"Pope","year":"2009","journal-title":"J. Immunol. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.blre.2017.08.006","article-title":"T cell acute lymphoblastic leukemia (T-ALL): New insights into the cellular origins and infiltration mechanisms common and unique among hematologic malignancies","volume":"32","author":"Vadillo","year":"2018","journal-title":"Blood Rev."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ren, A., Tong, X., Xu, N., Zhang, T., Zhou, F., and Zhu, H. (2023). CAR T-Cell Immunotherapy Treating T-ALL: Challenges and Opportunities. Vaccines, 11.","DOI":"10.3390\/vaccines11010165"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/leu.2009.223","article-title":"Targeted therapy in T-cell malignancies: Dysregulation of the cellular signaling pathways","volume":"24","author":"Zhao","year":"2010","journal-title":"Leukemia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5136","DOI":"10.1182\/blood-2009-08-231217","article-title":"T-cell acute lymphoblastic leukemia in adults: Clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII\/ECOG 2993)","volume":"114","author":"Marks","year":"2009","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1038\/bcj.2011.14","article-title":"Long-term complications and side effects after allogeneic hematopoietic stem cell transplantation: An update","volume":"1","author":"Mohty","year":"2011","journal-title":"Blood Cancer J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s40164-023-00384-4","article-title":"Targeted treatment of T-cell acute lymphoblastic leukemia: Latest updates from the 2022 ASH Annual Meeting","volume":"12","author":"Xu","year":"2023","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"106626","DOI":"10.1016\/j.leukres.2021.106626","article-title":"An antibody-drug conjugate with intracellular drug release properties showing specific cytotoxicity against CD7-positive cells","volume":"108","author":"Zhang","year":"2021","journal-title":"Leuk. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1046\/j.1365-2141.1996.d01-1900.x","article-title":"Therapy with CD7 monoclonal antibody TH-69 is highly effective for xenografted human T-cell ALL","volume":"95","author":"Baum","year":"1996","journal-title":"Br. J. Haematol."},{"key":"ref_27","first-page":"2848","article-title":"A recombinant CD7-specific single-chain immunotoxin is a potent inducer of apoptosis in acute leukemic T cells","volume":"62","author":"Peipp","year":"2002","journal-title":"Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"34070","DOI":"10.18632\/oncotarget.8710","article-title":"Novel CD7-specific nanobody-based immunotoxins potently enhanced apoptosis of CD7-positive malignant cells","volume":"7","author":"Tang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1089\/hum.2023.029","article-title":"Universal Anti-CD7 CAR-T Cells Targeting T-ALL and Functional Analysis of CD7 Antigen on T\/CAR-T Cells","volume":"34","author":"Xie","year":"2023","journal-title":"Hum. Gene Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1038\/s41375-023-02018-4","article-title":"CD7 targeted \u201coff-the-shelf\u201d CAR-T demonstrates robust in vivo expansion and high efficacy in the treatment of patients with relapsed and refractory T cell malignancies","volume":"37","author":"Li","year":"2023","journal-title":"Leukemia"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/1\/106\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:46:38Z","timestamp":1760103998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/1\/106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,15]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["biom14010106"],"URL":"https:\/\/doi.org\/10.3390\/biom14010106","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,15]]}}}