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Enhancement of CD70-specific CAR T treatment by IFN-γ released from oHSV-1-infected glioblastoma

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机构: [1]Capital Med Univ, Beijing Neurosurg Inst, Brain Tumor Res Ctr, Beijing 100070, Peoples R China [2]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing 100070, Peoples R China [3]Beijing Lab Biomed Mat, Beijing 100070, Peoples R China [4]Shandong Prov ENT Hosp, Shandong Prov Gen Hosp 2, Jinan 250031, Peoples R China [5]Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Ophthalmol & Visual Sci Key Lab, Beijing, Peoples R China
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关键词: CD70 Chimeric antigen receptor Glioblastoma Oncolytic herpes simplex virus-1 Immunotherapy Tumor microenvironment

摘要:
Even with progressive combination treatments, the prognosis of patients with glioblastoma (GBM) remains extremely poor. OV is one of the new promising therapeutic strategies to treat human GBM. OVs stimulate immune cells to release cytokines such as IFN-gamma during oncolysis, further improve tumor microenvironment (TME) and enhance therapeutic efficacy. IFN-gamma plays vital role in the apoptosis of tumor cells and recruitment of tumor-infiltrating T cells. We hypothesized that oncolytic herpes simplex virus-1 (oHSV-1) enhanced the antitumor efficacy of novel CD70-specific chimeric antigen receptor (CAR) T cells by T cell infiltration and IFN-gamma release. In this study, oHSV-1 has the potential to stimulate IFN-gamma secretion of tumor cells rather than T cell secretion and lead to an increase of T cell activity, as well as CD70-specific CAR T cells can specifically recognize and kill tumor cells in vitro. Specifically, combinational therapy with CD70-specific CAR T and oHSV-1 promotes tumor degradation by enhancing pro-inflammatory circumstances and reducing anti-inflammatory factors in vitro. More importantly, combined therapy generated potent antitumor efficacy, increased the proportion of T cells and natural killer cells in TME, and reduced regulatory T cells and transformed growth factor-beta 1 expression in orthotopic xenotransplanted animal model of GBM. In summary, we reveal that oHSV-1 enhance the therapeutic efficacy of CD70-spefific CAR T cells by intratumoral T cell infiltration and IFN-gamma release, supporting the use of CAR T therapy in GBM therapeutic strategies.

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出版当年[2021]版:
大类 | 2 区 医学
小类 | 3 区 肿瘤学 3 区 免疫学
最新[2023]版:
大类 | 2 区 医学
小类 | 3 区 免疫学 3 区 肿瘤学
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出版当年[2020]版:
Q1 ONCOLOGY Q1 IMMUNOLOGY
最新[2023]版:
Q1 ONCOLOGY Q2 IMMUNOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

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第一作者机构: [1]Capital Med Univ, Beijing Neurosurg Inst, Brain Tumor Res Ctr, Beijing 100070, Peoples R China [2]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing 100070, Peoples R China [3]Beijing Lab Biomed Mat, Beijing 100070, Peoples R China [4]Shandong Prov ENT Hosp, Shandong Prov Gen Hosp 2, Jinan 250031, Peoples R China
通讯作者:
通讯机构: [1]Capital Med Univ, Beijing Neurosurg Inst, Brain Tumor Res Ctr, Beijing 100070, Peoples R China [2]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing 100070, Peoples R China [3]Beijing Lab Biomed Mat, Beijing 100070, Peoples R China
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