BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Qianqian Wang,Xin Yuan,Cuijuan Liu,Ying Huang,Lin Li,Yimin Zhu
CAR-T cell therapy has been proven to be effective on hematological tumors, although graft-versus-host disease and cytokine release syndrome(CRS) limit its application to a certain extent. However, CAR-T therapy for solid tumors met challenges, among which the lack of tumor-specific antigens (TSA) and immunosuppressive tumor microenvironment (TME) are the most important factors. CAR-NK could be a good alternative to CAR-T in some ways since they can induce mild CRS and are independent of HLA-matching, but the efficacy of CAR-NKs remains limited in solid tumors. CAR cells armed with multiple tumor targeting molecules may obtain higher therapeutic efficacy against solid tumors. Due to large molecular weight, multivalent scFvs cannot be displayed efficiently on T cells and the high affinity of scFv to the target makes it easy to cause on-target, off-tumor(OTOT) toxicity. Peptides with low molecular weight and slightly lower affinity than scFvs allow immune cells to display multiple peptides to increase killing ability and reduce OTOT toxicity. In our study, peptide-based CAR-NK cells were designed to solve the dilemma of CAR-T in solid tumors. Firstly, the peptide-based CAR-NK92MI cells with A1 peptide were constructed and their inhibitory effects on the growth of A549 tumor cells were identified. Secondly, the tri-specific CAR-NK92MI cells with peptides that simultaneously targeted PD-L1, EGFR and VEGFR2 were developed for the combinatory therapy. Tri-specific CAR-NK92MI exhibited comparable killing activities to scFv-based CAR-NK92MI. Moreover, peptide-based CAR NK92MI mitigated OTOT toxicity. Our study implied that peptide-based CAR-NKs could behave as promising tools in solid tumor
研究领域:
免疫学
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肿瘤学
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细胞治疗
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产品关联
DOI
PubMed
高影响因子
BMC CANCER
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2025
·Vol. 25
·期 1
·1-10
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IF 3.4
Liu Shiyuan,Guan Tian,Yang Futian,Zhang Honglei,Yao Yao,Huang Jiman,Zhao Pengfei,Huang Wei,Wu Tailiang,Lin Hui,Fu Ting,Chen Shaoyu,Dai Pengzhan,Ding Zhechun,Chen Dongmei,Li Wei,Zeng Haoyu,Zhang Xianjun
Human oral tongue squamous cell carcinoma (OTSCC) is a prevalent form of head and neck squamous cell carcinoma (HNSCC), often presenting at an advanced stage with a grim prognosis. Traditional therapeutic approaches such as surgery, adjuvant radiotherapy, and chemoradiotherapy have shown limited efficacy in treating advanced OTSCC, underscoring the urgent need for innovative treatment strategies. Our bioinformatics analysis identified CD276 as a significant biomarker in OTSCC, with high protein expression levels correlating to a markedly reduced survival rate in late-stage patients. This discovery has led us to develop chimeric antigen receptor-natural killer (CAR-NK) cells derived from umbilical cord blood cells (UCBCs), specifically targeting CD276. Our aim is to investigate this novel therapeutic approach for its potential to combat OTSCC under pre-clinical conditions. Our in vitro and ex vivo studies have demonstrated that CD276-targeted CAR-NK cells exhibit remarkable efficacy in lysing OTSCC cell lines and primary cells, as well as in eliminating OTSCC organoids. These promising results underscore the pivotal role of CD276 in OTSCC pathogenesis and highlight the potential of CAR-NK cell therapy as a groundbreaking treatment option for advanced-stage OTSCC, offering new hope for translational medicine in the field of stomatology.
研究领域:
肿瘤学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
Future Science OA
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2024
·
IF 2.4
Yan Zhu,Luanhong Wang,Biyu Jiang,Yini Wang,Qing Wu,Sihua Hong,Xiaojing Wang,Yuancheng Li,Tian Guan,Haoyu Zeng,Congzhu Li
Aim: This study aimed to explore using peripheral blood mononuclear cell (PBMC)-derived chimeric antigen receptor (CAR) NK cells targeting ROBO1 as a personalized medicine approach for ovarian cancer. Methods: A two-step strategy generated ROBO1-targeted CAR NK cells from PBMCs of ovarian cancer patients. Efficacy was evaluated using xCELLigence RTCA, CCK-8 and Live/Dead fluorescence assays. Results: ROBO1-NK cells exhibited higher efficiency in eradicating primary ovarian cancer cells and lysing ovarian tumor organoids compared with primary NK cells without ROBO1-CAR modification. Conclusion: These findings highlight the potential of developing ROBO1-targeted CAR-NK cells from patients' PBMCs as a personalized treatment option for ovarian cancer.
研究领域:
肿瘤学
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免疫治疗
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2024
·
IF 18
Zilin Tan,Liangjie Tian,Yang Luo,Kexin Ai,Xuehua Zhang,Haitao Yuan,Jinfan Zhou,Guangyao Ye,Shuofei Yang,Ming Zhong,Gaohua Li,Yanan Wang
Colorectal cancer (CRC) recurrence post-surgery remains a major challenge. While Chimeric Antigen Receptor (CAR)-engineered natural killer (NK) cells hold immense therapeutic potential, their intratumoral infiltration ability remains limited, hampering efficacy. Building upon prior research suggesting that chemokines like C-X-C motif chemokine ligand 9 (CXCL9) and C-X-C motif chemokine ligand 10 (CXCL10) recruit CAR-NK cells, we hypothesized that tumor cell m6A methylation, regulated by Methyltransferase-like 3 (METTL3), influences chemokine secretion. This study aims to elucidate the underlying mechanisms and improve METTL3 inhibition efficiency. We designed an adhesive hemostasis hydrogel loaded with STM2457, a METTL3 inhibitor, aimed at sustained release in the acidic tumor microenvironment. In vitro, the hydrogel promoted CAR-NK cell recruitment and tumor killing via sustained METTL3 inhibition. The hydrogel's Schiff base bonds further enabled intestinal adhesion and hemostasis in an incomplete tumor resection model of CRC. Combining the hydrogel with CAR-NK cell therapy significantly reduced CRC recurrence in vivo. Overall, our study reveals the crucial role of METTL3 in CRC recurrence and proposes a promising, multimodal strategy using STM2457-loaded hydrogel and CAR-NK cells for enhanced therapeutic efficacy.
研究领域:
肿瘤学
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分子生物学
·
免疫疗法
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
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