{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:22:46Z","timestamp":1787167366290,"version":"build-2736575974"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Shanghai Science and Technology Development Funds","award":["23YF1458800"],"award-info":[{"award-number":["23YF1458800"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["GZC20233559"],"award-info":[{"award-number":["GZC20233559"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research Fund for the Basic Medical Research for the youth of the Changhai Hospital","award":["2023QD24"],"award-info":[{"award-number":["2023QD24"]}]},{"name":"Research Fund for the Basic Medical Research for the youth of Naval Medical University","award":["2024QN024"],"award-info":[{"award-number":["2024QN024"]}]},{"name":"National Natural Science Foundation of China (NSFC) Youth Program","award":["82100162"],"award-info":[{"award-number":["82100162"]}]},{"name":"Medical-enterprise Integration Innovation and Collaboration Project","award":["SHDC2023CRT005"],"award-info":[{"award-number":["SHDC2023CRT005"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82270202"],"award-info":[{"award-number":["82270202"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Hematol Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Chimeric antigen receptor T cell (CAR-T) is the main salvage therapy for relapsed or refractory large B-cell lymphoma (r\/r LBCL). However, over 50% of patients relapse after CAR-T therapy. In this work, we transduced the CAR gene into hematopoietic stem cells (HSCs) using a lentiviral vector. Chimeric antigen receptor-modified HSC (CAR-HSCs) were transplanted into mice after lethal irradiation. CAR gene transduction did not compromise the ability of HSCs to expand, self-renew, or reconstitute. CAR was expressed on T cells, natural killer cells, B cells, monocytes, and neutrophils in the peripheral blood. CAR-HSCs transplantation significantly reduced CD19\n                    <jats:sup>+<\/jats:sup>\n                    tumor burden and prolonged the survival of mice with preclinical tumor without severe toxicity. CAR-HSCs also differentiated into different CAR-expressing immune cells that reshaped the tumor microenvironment by increasing the proportion of antitumor cells (like CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells) and the antitumor response, and by decreasing immunosuppressive cells, such as tumor-associated macrophage subtype 2. This study demonstrated a preclinical proof-of-principle for CAR-HSCs therapy in r\/r LBCL, suggesting an opportunity for its clinical translation.\n                  <\/jats:p>","DOI":"10.1186\/s40164-025-00715-7","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T11:14:49Z","timestamp":1761131689000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Chimeric antigen receptor modified hematopoietic stem cells (CAR-HSCs) arm all immune forces for anti-tumor in mice"],"prefix":"10.1186","volume":"14","author":[{"given":"Tao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongliang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongge","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gusheng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"715_CR1","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1056\/NEJMoa2116133","volume":"386","author":"FL Locke","year":"2022","unstructured":"Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, et al. Axicabtagene Ciloleucel as Second-Line therapy for large B-Cell lymphoma. N Engl J Med. 2022;386:640\u201354.","journal-title":"N Engl J Med"},{"key":"715_CR2","doi-asserted-by":"publisher","first-page":"2294","DOI":"10.1016\/S0140-6736(22)00662-6","volume":"399","author":"M Kamdar","year":"2022","unstructured":"Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, et al. Lisocabtagene Maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet (London England). 2022;399:2294\u2013308.","journal-title":"Lancet (London England)"},{"key":"715_CR3","doi-asserted-by":"crossref","unstructured":"Jain MD, Spiegel JY, Nastoupil LJ, Tamaresis J, Ghobadi A, Lin Y et al. Five-Year Follow-Up of Standard-of-Care Axicabtagene Ciloleucel for large B-Cell lymphoma: results from the US lymphoma CAR T consortium. J Clin Oncology: Official J Am Soc Clin Oncol 2024: JCO2302786.","DOI":"10.1200\/JCO.23.02786"},{"key":"715_CR4","doi-asserted-by":"crossref","unstructured":"Rakhshandehroo T, Mantri SR, Moravej H, Louis BBV, Salehi Farid A, Munaretto L et al. A CAR enhancer increases the activity and persistence of CAR T cells. Nat Biotechnol 2024.","DOI":"10.1038\/s41587-024-02339-4"},{"key":"715_CR5","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1126\/science.abc1855","volume":"371","author":"RA Hernandez-Lopez","year":"2021","unstructured":"Hernandez-Lopez RA, Yu W, Cabral KA, Creasey OA, Lopez Pazmino MDP, Tonai Y, et al. T cell circuits that sense antigen density with an ultrasensitive threshold. 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