{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:10:17Z","timestamp":1789236617684,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009334","name":"Pearl River S and T Nova Program of Guangzhou","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>B7-H3 is over-expressed in multiple types of solid tumors, making it an ideal target for chimeric antigen receptor (CAR)-T therapy. Here, we first report a case of multiple basal cell carcinoma (BCC) patient treated with humanized monoclonal anti-B7-H3 CAR-T cells through direct intratumoral injection. After three dose-escalated injections, the lesion in the abdomen decreased by 40% in volume, shrank from bulging to flat, but was not eradicated completely. The large lesion in the forehead became dry from original ulcer and bleeding. The adverse events observed were itching, myalgia, and redness. Immunohistochemistry analysis demonstrated that B7-H3-positive tumor cells and B7-H3 expression intensity were reduced after injections of CAR-T cells. The number of infiltrating CD3 T cells increased significantly but mainly located outside the tumor region. Subsequently, high levels of TGF-\u03b2 in the tumor area were observed, suggesting that solid tumor microenvironment may hinder the infiltration and effect of CAR-T cells. In summary, in this particular case report, intratumoral injection of B7-H3 CAR-T cells partially controls tumor growth in the BCC patient with minor adverse events. The efficacy and safety of B7-H3 CAR-T therapy need to be further investigated with a larger cohort of patients. Although only one clinical case is reported here, the anti-B7-H3 CAR-T cell therapy should be considered as a treatment option for solid tumors in the future. This clinical trial was registered at the Chinese Clinical Trial Registry (<jats:uri>www.chictr.org.cn<\/jats:uri>) with registration number ChiCTR2100044386.<\/jats:p>","DOI":"10.3389\/fonc.2022.956593","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T07:51:15Z","timestamp":1660722675000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Case report: B7-H3 CAR-T therapy partially controls tumor growth in a basal cell carcinoma patient"],"prefix":"10.3389","volume":"12","author":[{"given":"Gang","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangchao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongwei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taoyuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junnan","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingheng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renliang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsheng","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1817226","article-title":"Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma","volume":"380","author":"Raje","year":"2019","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709866","article-title":"Tisagenlecleucel in children and young adults with b-cell lymphoblastic leukemia","volume":"378","author":"Maude","year":"2018","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00128","article-title":"CAR T cells for solid tumors: New strategies for finding, infiltrating, and surviving in the tumor microenvironment","volume":"10","author":"Martinez","year":"2019","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.41105","article-title":"B7-H3, a checkpoint molecule, as a target for cancer immunotherapy","volume":"16","author":"Yang","year":"2020","journal-title":"Int J Biol Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26238","article-title":"B7-H3 contributes to the metastatic capacity of melanoma cells by modulation of known metastasis-associated genes","volume":"130","author":"Tekle","year":"2012","journal-title":"Int J Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00264","article-title":"B7H3 as a promoter of metastasis and promising therapeutic target","volume":"8","author":"Dong","year":"2018","journal-title":"Front Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0821-8","article-title":"Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid\/rhabdoid tumors","volume":"26","author":"Theruvath","year":"2020","journal-title":"Nat Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0432","article-title":"CAR T cells targeting B7-H3, a pan-cancer antigen, demonstrate potent preclinical activity against pediatric solid tumors and brain tumors","volume":"25","author":"Majzner","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.7150\/thno.43991","article-title":"Tandem CAR-T cells targeting CD70 and B7-H3 exhibit potent preclinical activity against multiple solid tumors","volume":"10","author":"Yang","year":"2020","journal-title":"Theranostics"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12599","article-title":"Immunoregulatory protein B7-H3 promotes growth and decreases sensitivity to therapy in metastatic melanoma cells","volume":"30","author":"Flem-Karlsen","year":"2017","journal-title":"Pigment Cell Melanoma Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-018-2138-8","article-title":"PD-L1, B7-H3, and PD-1 expression in immunocompetent vs. immunosuppressed patients with cutaneous squamous cell carcinoma","volume":"67","author":"Varki","year":"2018","journal-title":"Cancer Immunol Immunother"},{"key":"B12","doi-asserted-by":"publisher","first-page":"5572","DOI":"10.3390\/ijms21155572","article-title":"Basal cell carcinoma: A comprehensive review","volume":"21","author":"Dika","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2018.03.060","article-title":"Basal cell carcinoma: Epidemiology; pathophysiology; clinical and histological subtypes; and disease associations","volume":"80","author":"Cameron","year":"2019","journal-title":"J Am Acad Dermatol"},{"key":"B14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.5070\/D373C4H22M","article-title":"Basal cell carcinoma does metastasize","volume":"14","author":"Ozgediz","year":"2008","journal-title":"Dermatol Online J"},{"key":"B15","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1177\/1060028013506696","article-title":"Vismodegib: an inhibitor of the hedgehog signaling pathway in the treatment of basal cell carcinoma","volume":"48","author":"Proctor","year":"2014","journal-title":"Ann Pharmacother"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-018-0006-z","article-title":"Delivery technologies for cancer immunotherapy","volume":"18","author":"Riley","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0522-3","article-title":"Clonal replacement of tumor-specific T cells following PD-1 blockade","volume":"25","author":"Yost","year":"2019","journal-title":"Nat Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s40425-018-0439-2","article-title":"Resistance to anti-PD-1-based immunotherapy in basal cell carcinoma: A case report and review of the literature","volume":"6","author":"Sabbatino","year":"2018","journal-title":"J Immunother Cancer"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.34213","article-title":"Current progress in CAR-T cell therapy for solid tumors","volume":"15","author":"Ma","year":"2019","journal-title":"Int J Biol Sci"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.09.006","article-title":"Combination immunotherapy with CAR T cells and checkpoint blockade for the treatment of solid tumors","volume":"36","author":"Grosser","year":"2019","journal-title":"Cancer Cell"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav8692","article-title":"Enhanced CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor","volume":"365","author":"Ma","year":"2019","journal-title":"Science"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.107419","article-title":"Clinical investigation of CAR T cells for solid tumors: Lessons learned and future directions","volume":"205","author":"Bagley","year":"2020","journal-title":"Pharmacol Ther"},{"key":"B23","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.ccell.2017.03.005","article-title":"Eradication of tumors through simultaneous ablation of CD276\/B7-H3-Positive tumor cells and tumor vasculature","volume":"31","author":"Seaman","year":"2017","journal-title":"Cancer Cell"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2020.03.019","article-title":"B7-H3-Targeted CAR-T cells exhibit potent antitumor effects on hematologic and solid tumors","volume":"17","author":"Zhang","year":"2020","journal-title":"Mol Ther Oncolytics"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-2540","article-title":"Preclinical evaluation of B7-H3-specific chimeric antigen receptor T cells for the treatment of acute myeloid leukemia","volume":"27","author":"Lichtman","year":"2021","journal-title":"Clin Cancer Res"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2020.100770","article-title":"Efficacy of B7-H3-Redirected BiTE and CAR-T immunotherapies against extranodal nasal natural Killer\/T cell lymphoma","volume":"13","author":"Zheng","year":"2020","journal-title":"Transl Oncol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2019.07.002","article-title":"B7-H3 as a novel CAR-T therapeutic target for glioblastoma","volume":"14","author":"Tang","year":"2019","journal-title":"Mol Ther Oncolytics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.ccell.2019.01.002","article-title":"Antitumor responses in the absence of toxicity in solid tumors by targeting B7-H3 via chimeric antigen receptor T cells","volume":"35","author":"Du","year":"2019","journal-title":"Cancer Cell"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e1137","DOI":"10.1002\/cti2.1137","article-title":"Bioactivity and safety of B7-H3-targeted chimeric antigen receptor T cells against anaplastic meningioma","volume":"9","author":"Tang","year":"2020","journal-title":"Clin Transl Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s13045-020-01024-8","article-title":"Targeting B7-H3 via chimeric antigen receptor T cells and bispecific killer cell engagers augments antitumor response of cytotoxic lymphocytes","volume":"14","author":"Liu","year":"2021","journal-title":"J Hematol Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1610497","article-title":"Regression of glioblastoma after chimeric antigen receptor T-cell therapy","volume":"375","author":"Brown","year":"2016","journal-title":"N Engl J Med"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.956593\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T01:28:34Z","timestamp":1676424514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.956593\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,17]]},"references-count":31,"alternative-id":["10.3389\/fonc.2022.956593"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.956593","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,17]]},"article-number":"956593"}}