As the main element components of the operational program, both SpyTag and SpyCatcher sequences derive from and xenograft mouse versions demonstrated our divide CAR-T program possesses therapeutic results comparable with those of conventional anti-hGPC3 CAR-T cells, which the machine has robust flexibility and decreased unwanted effects, especially CRS. by Xuan Liu, Jianyun Wen, Honglei Yi, Xiaorui Hou, Yue Yin, Guofu Ye, Xuedong Wu and Xiaotao Jiang in Therapeutic Improvements in Medical Oncology fig_S2 C Supplemental material for Split chimeric antigen receptor-modified T cells targeting glypican-3 suppress hepatocellular carcinoma growth with reduced cytokine release fig_S2.tif (4.5M) GUID:?BEA7A11B-45F8-4712-BF5D-1E2508C359EE Supplemental material, fig_S2 for Split chimeric antigen receptor-modified T cells targeting glypican-3 suppress hepatocellular carcinoma growth with reduced cytokine release by Xuan Liu, Jianyun Wen, Honglei Yi, Xiaorui Hou, Yue Yin, Guofu Ye, Xuedong Wu and Xiaotao Jiang in Therapeutic Improvements in Medical Oncology fig_S3 C Supplemental material for Split chimeric antigen receptor-modified T cells targeting glypican-3 suppress hepatocellular carcinoma growth with reduced cytokine release fig_S3.tif (586K) GUID:?159B7153-2E97-44EF-AEA2-3077C7559F89 Supplemental material, fig_S3 for Split chimeric antigen receptor-modified T cells targeting glypican-3 suppress hepatocellular carcinoma growth with reduced cytokine release by Xuan Liu, m-Tyramine Jianyun Wen, Honglei Yi, Xiaorui Hou, Yue Yin, Guofu Ye, Xuedong Wu and Xiaotao Jiang in Therapeutic Advances in Medical Oncology fig_S4 C Supplemental material for Split chimeric antigen receptor-modified T cells targeting glypican-3 suppress hepatocellular m-Tyramine carcinoma growth with reduced cytokine release fig_S4.tif (324K) GUID:?5E9312FA-8457-445E-AB35-9A5AE8788CB6 Supplemental material, fig_S4 for Split chimeric antigen receptor-modified T cells targeting glypican-3 suppress hepatocellular carcinoma growth with reduced cytokine release by Xuan Liu, Jianyun Wen, Honglei Yi, Xiaorui Hou, Yue Yin, Guofu Ye, Xuedong Wu and Xiaotao Jiang in Therapeutic Advances in Medical m-Tyramine Oncology Table_S1 C Supplemental material for Split chimeric antigen receptor-modified T cells targeting glypican-3 suppress hepatocellular carcinoma growth with reduced cytokine release Table_S1.doc (34K) GUID:?65CB35BC-7175-48CB-A293-79C09C0D0035 Supplemental material, Table_S1 for Split chimeric antigen receptor-modified T cells targeting glypican-3 suppress hepatocellular carcinoma growth with reduced cytokine release by Xuan Liu, Jianyun TEL1 Wen, Honglei Yi, Xiaorui Hou, Yue Yin, Guofu Ye, Xuedong Wu and Xiaotao Jiang in Therapeutic Advances in Medical Oncology Abstract Background: Human glypican-3 (hGPC3) is a protein highly expressed in hepatocellular carcinoma (HCC) but limited in normal tissues, making m-Tyramine it an ideal target for immunotherapy. The adoptive transfer of hGPC3-specific chimeric antigen receptor T (CAR-T) cells for HCC treatment has been conducted in clinical trials. Due to the rigid construction, standard CAR-T cells have some intrinsic limitations, like uncontrollable overactivation and inducing severe cytokine release syndrome. Methods: We redesigned the hGPC3-specific CAR by splitting the traditional CAR into two parts. By using coculturing assays and a xenograft mouse model, the and cytotoxicity and cytokine release of the split anti-hGPC3 CAR-T cells were evaluated against numerous HCC cell lines and compared with standard CAR-T cells. Results: data exhibited that split anti-hGPC3 CAR-T cells could identify and lyse hGPC3+ HepG2 and Huh7 cells in a dose-dependent manner. Impressively, split anti-hGPC3 CAR-T cells produced and released a significantly lower amount of proinflammatory cytokines, including IFN-, TNF-, IL-6, and GM-CSF, than standard CAR-T cells. When injected into immunodeficient mice inoculated subcutaneously with HepG2 cells, our split anti-hGPC3 CAR-T cells could suppress HCC tumor growth, but released significantly lower levels of cytokines than standard CAR-T cells. Conclusions: We describe here for the first time the use of split anti-hGPC3 CAR-T cells to treat HCC; split anti-hGPC3 CAR-T cells could suppress tumor growth and reduce cytokine release, and represent a more versatile and safer alternative to standard CAR-T cells treatment. and cytotoxicity and cytokine release results demonstrated that our split anti-hGPC3 CAR-T cells can control the growth of HCC with decreased cytokine release compared with standard CAR-T cells. This novel split anti-hGPC3 CAR system represents a more versatile and safer application for HCC treatment without compromising CAR-T cell efficacy. Methods Ethics statement All animal experiments were approved by The Institutional Laboratory Animal Care and Use Committee at Southern Medical University or college, Guangzhou, P.R. China (IACUC 81671570). All experiments involving human specimens were conducted within the guidelines of the 1975 Declaration of Helsinki, and were approved by the Ethical Committee of Nanfang Hospital, Guangzhou, P.R. China (approval number NFEC-2015-140). Written informed consent that covered the introduction and purpose of the study, potential risks and discomforts, confidentiality, voluntary participation, and authorization was obtained from all healthy donors. Cell lines and culture media Human embryonic kidney 293T cells, human HCC HepG2 cells were obtained from.