更新于：2024-12-18
Beijing Chineo Medical Technology Co., Ltd
更新于：2024-12-18
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A Phase I Clinical Study to Evaluate the Safety, the Tolerability, the Pharmacokinetic Characteristics and the Efficacy of ScTIL Injection (Genetically Modified Tumor Infiltrating Lymphocytes) in the Treatment of Advanced Malignant Solid Tumors
A Open, Single Arm, Phase IIa Clinical Study on the Safety, Pharmacokinetics, and Efficacy of ScTIL (Genetically Modified Tumor Infiltrating Lymphocytes) in the Treatment of Gynecological Malignancies
100 项与 北京卡替医疗技术有限公司 相关的临床结果
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2024-12-03Cancer Immunology Research
Peripheral Blood-Derived PD-1/CD28-CD19 CAR-Modified PD-1+ T-Cell Therapy in Patients with Solid Tumors.
Article
作者: Shen, Chunyi ; Zhang, Yi ; Song, Lijie ; Chen, Xinfeng ; Zhao, Jie ; Mou, Xiaoning ; Liu, Yaqing ; Miao, Lijun ; Zhao, Xuan ; Zhao, Qitai ; Gu, Weiyue ; Li, Congcong ; Zhang, Zhen ; Guo, Fuyou
T cells expressing programmed cell death 1 (PD-1) in the peripheral blood (PB) of patients with tumors possess therapeutic potential; however, the immunosuppressive, PD-1-triggered signaling pathway and limited proliferative capacity of PD-1+ T cells present challenges to their therapeutic application. Here, we observed no discernible distinction between PD-1+ and PD-1- T cells in terms of clonal overlap. However, CD8+PD-1+ T cells from PB and tumor tissues exhibited tighter clustering based on clone size. Single-cell RNA sequencing analysis showed that PD-1+ T cells from PB highly expressed cytotoxicity-related genes and were enriched for T-cell activation-related pathways compared with PD-1- T cells from PB or tumor tissues. Consistent with this, PB-derived PD-1+ T cells exhibited strong cytotoxicity toward autologous tumor cells and tumor cell lines. To augment PD-1+ T-cell activity against solid tumors in vivo, we introduced a PD-1/CD28 fusion receptor combined with a CD19 chimeric antigen receptor into PD-1+ T cells, which were then expanded in vitro. The modified PD-1+ T cells exhibited superior proliferation and antitumor abilities in vitro. In addition, four patients with cancer were infused with autologous PD-1/CD28-CD19 chimeric antigen receptor PD-1+ T cells. None of these patients experienced severe side effects, and one patient with melanoma achieved a complete response that was maintained for 6.7 months. The three other patients had stable disease. Collectively, these results suggested that cell therapy with modified PB-derived PD-1+ T cells is both safe and effective, and it may constitute a promising treatment strategy for patients with cancer.
2024-06-01BIOMEDICINE & PHARMACOTHERAPY
PD-1-CD28-enhanced receptor and CD19 CAR-modified tumor-infiltrating T lymphocytes produce potential anti-tumor ability in solid tumors
Article
作者: Zhao, Jie ; Zhang, Yi ; Mou, Xiaoning ; Zhang, Mingzhi ; Zhang, Xudong ; Wang, Liping ; Wang, Feng ; Liu, Yanfen ; Zhao, Xuan ; Gu, Weiyue ; Chen, Xinfeng ; Huang, Jianmin ; Zhang, Zhen
The limited expansion ability and functional inactivation of T cells within the solid tumor microenvironment are major problems faced during in the application of using tumor-infiltrating lymphocytes (TILs) in vivo. We sought to determine whether TILs carrying a PD-1-CD28-enhanced receptor and CD19 CAR could overcome this limitation and mediate tumor regression. First, anti-tumor effects of PD-1-CD28-enhanced receptor or CD19 CAR modified NY-ESO-1-TCR-T cells to mimic the TILs function (hereafter "PD-1-CD28-TCR-T" or "CD19 CAR-TCR-T" cells, respectively) were tested using the NY-ESO-1 over-expressed tumor cell line in vitro and in a tumor-bearing model. Furthermore, the safety and anti-tumor ability of S-TILs (TILs modified through transduction with a plasmid encoding the PD-1-CD28-T2A-CD19 CAR) were evaluated in vivo. PD-1-CD28-TCR-T cells showed a formidable anti-tumor ability that was not subject to PD-1/PD-L1 signaling in vivo. CD19 CAR-TCR-T cells stimulated with CD19+ B cells exhibited powerful expansion and anti-tumor abilities both in vitro and in vivo. Three patients with refractory solid tumors received S-TILs infusion. No treatment-related mortality was observed, and none of the patients experienced serious side effects. One patient with melanoma achieved a partial response, and two patients with colon or kidney cancer achieved long-term stable disease following S-TILs therapy. To the best of our knowledge, this is the first study describing the safety and efficacy of the adoptive transfer of autologous S-TILs to control disease in patients with advanced cancers, suggesting that S-TILs may be a promising alternative therapy for cancer.
2020-01-01Clinical immunology (Orlando, Fla.)
Neoantigen-activated haploidentical T cell therapy for angioimmunoblastic T-cell lymphoma
Letter
作者: Chen, Haimei ; Chen, Yuan ; Gu, Weiyue ; Hu, Guoyu
This study detected the tumor-specific mutations through next-generation sequencing, synthesized neoantigen mRNA in vitro, made a dendritic cell (DC) vaccine directed at neoantigen and used haploidentical T cells activated by DC vaccine as effector cells to treat a refractory angioimmunoblastic T-cell lymphoma (AITL).A 72-yr-old man, with 1 mo of systemic lymphadenopathy, was admitted to the hospital on March 24, 2017, and phys. examination showed multiple lymphadenectasis at neck, bilateral axillas and inguens.Next-generation sequencing of circulating tumor DNA (ctDNA) showed mutations in gene RHOA, TET2, DNMT3A, NOTCH1, MEF2B.They used the DCs transfected with neoantigen mRNA to stimulate haploidentical T cell to treat a refractory AITL for T cells from healthy donor have normal functions and may contain less regulatory T cells than T cells from the tumor.The results suggests that neoantigen-activated haploidentical T cell therapy can be effective in controlling T-cell lymphoma.
100 项与 北京卡替医疗技术有限公司 相关的药物交易
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100 项与 北京卡替医疗技术有限公司 相关的转化医学
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