BACKGROUNDCancer immunotherapy, particularly immune checkpoint inhibitors (ICBs) such as anti-PD-1 antibodies, has revolutionised cancer treatment, although response rates vary among patients. Previous studies have demonstrated that caerin 1.1 and 1.9, host-defence peptides from the Australian tree frog, enhance the effectiveness of anti-PD-1 and therapeutic vaccines in a murine TC-1 model by activating tumour-associated macrophages intratumorally.METHODSWe employed a murine B16 melanoma model to investigate the therapeutic potential of caerin 1.1 and 1.9 in combination with anti-CD47 and a therapeutic vaccine (triple therapy, TT). Tumour growth of caerin-injected primary tumours and distant metastatic tumours was assessed, and survival analysis conducted. Single-cell RNA sequencing (scRNAseq) of CD45⁺ cells isolated from distant tumours was performed to elucidate changes in the tumour microenvironment induced by TT.RESULTSThe TT treatment significantly reduced tumour volumes on the treated side compared to untreated and control groups, with notable effects observed by Day 21. Survival analysis indicated extended survival in mice receiving TT, both on the treated and distant sides. scRNAseq revealed a notable expansion of conventional type 1 dendritic cells (cDC1s) and CD4⁺CD8⁺ T cells in the TT group. Tumour-associated macrophages in the TT group shifted toward a more immune-responsive M1 phenotype, with enhanced communication observed between cDC1s and CD8⁺ and CD4⁺CD25⁺ T cells. Additionally, TT downregulated M2-like macrophage marker genes, particularly in MHCIIhi and tissue-resident macrophages, suppressing Cd68 and Arg1 expression across all macrophage types. Differential gene expression analysis highlighted pathway alterations, including upregulation of oxidative phosphorylation and MYC target V1 in Arg1^hi macrophages, and activation of pro-inflammatory pathways in MHCII^hi and tissue-resident macrophages.CONCLUSIONOur findings suggest that caerin 1.1 and 1.9, combined with immunotherapy, effectively modulate the tumour microenvironment in primary and secondary tumours, leading to reduced tumour growth and enhanced systemic immunity. Further investigation into these mechanisms could pave the way for improved combination therapies in advanced melanoma treatment.

Caerin 1.1 and 1.9 peptides halt B16 melanoma metastatic tumours via expanding cDC1 and reprogramming tumour macrophages

作者: Fu, Quanlan ; Li, Junjie ; Wang, Tianfang ; Ni, Guoying ; Li, Hejie ; Liu, Xiaosong ; Luo, Yuandong ; Chen, Zhu

Abstract

Background Cancer immunotherapy, particularly immune checkpoint inhibitors (ICBs) such as anti-PD-1 antibodies, has revolutionized cancer treatment, although response rates vary among patients. Previous studies have demonstrated that caerin 1.1 and 1.9, host-defence peptides from the Australian tree frog, enhance the effectiveness of anti-PD-1 and therapeutic vaccines in a murine TC-1 model by activating tumour-associated macrophages intratumorally. Methods We employed a murine B16 melanoma model to investigate the therapeutic potential of caerin 1.1 and 1.9 in combination with anti-CD47 and a therapeutic vaccine (triple therapy, TT). Tumour growth of caerin-injected primary tumours and distant metastatic tumours was assessed, and survival analysis conducted. Single-cell RNA sequencing (scRNAseq) of CD45⁺ cells isolated from distant tumours was performed to elucidate changes in the tumour microenvironment induced by TT. Results The TT treatment significantly reduced tumour volumes on the treated side compared to untreated and control groups, with notable effects observed by Day 21. Survival analysis indicated extended survival in mice receiving TT, both on the treated and distant sides. scRNAseq revealed a notable expansion of conventional type 1 dendritic cells (cDC1s) and CD4⁺CD8⁺ T cells in the TT group. Tumour-associated macrophages in the TT group shifted toward a more immune-responsive M1 phenotype, with enhanced communication observed between cDC1s and CD8⁺ and CD4⁺CD25⁺ T cells. Additionally, TT downregulated M2-like macrophage marker genes, particularly in MHCIIhi and tissue-resident macrophages, suppressing Cd68 and Arg1 expression across all macrophage types. Differential gene expression analysis highlighted pathway alterations, including upregulation of oxidative phosphorylation and MYC target V1 in Arg1^hi macrophages, and activation of pro-inflammatory pathways in MHCII^hi and tissue-resident macrophages. Conclusion Our findings suggest that caerin 1.1 and 1.9, combined with immunotherapy, effectively modulate the tumour microenvironment in primary and secondary tumours, leading to reduced tumour growth and enhanced systemic immunity. Further investigation into these mechanisms could pave the way for improved combination therapies in advanced melanoma treatment.

PLOS ONE

Host-defence caerin 1.1 and 1.9 peptides suppress glioblastoma U87 and U118 cell proliferation through the modulation of mitochondrial respiration and induce the downregulation of CHI3L1

Article

作者: Ni, Guoying ; Liu, Xiaosong ; Zhang, Wei ; Wang, Tianfang ; Wang, Yichen ; Zhong, Furong ; Li, Junjie ; Xiao, Fengyun

Glioblastoma, the most aggressive form of brain cancer, poses a significant global health challenge with a considerable mortality rate. With the predicted increase in glioblastoma incidence, there is an urgent need for more effective treatment strategies. In this study, we explore the potential of caerin 1.1 and 1.9, host defence peptides derived from an Australian tree frog, in inhibiting glioblastoma U87 and U118 cell growth. Our findings demonstrate the inhibitory impact of caerin 1.1 and 1.9 on cell growth through CCK8 assays. Additionally, these peptides effectively curtail the migration of glioblastoma cells in a cell scratch assay, exhibiting varying inhibitory effects among different cell lines. Notably, the peptides hinder the G0/S phase replication in both U87 and U118 cells, pointing to their impact on the cell cycle. Furthermore, caerin 1.1 and 1.9 show the ability to enter the cytoplasm of glioblastoma cells, influencing the morphology of mitochondria. Proteomics experiments reveal intriguing insights, with a decrease in CHI3L1 expression and an increase in PZP and JUNB expression after peptide treatment. These proteins play roles in cell energy metabolism and inflammatory response, suggesting a multifaceted impact on glioblastoma cells. In conclusion, our study underscores the substantial anticancer potential of caerin 1.1 and 1.9 against glioblastoma cells. These findings propose the peptides as promising candidates for further exploration in the realm of glioblastoma management, offering new avenues for developing effective treatment strategies.

项与中奥生物医药技术（广东）有限公司相关的新闻（医药）

2024-12-01

·信狐药迅

艺妙神州/华东医药独家-商业化IM19 CAR-T细胞注射液提交上市申请|新受理（11.25-12.1）

本周药品注册受理数据，分门别类呈现，一目了然。(11.25-12.1）新药上市申请药品名称企业注册分类受理号苯磺酸氨氯地平颗粒广东东阳光药业股份有限公司2.2CXHS2400126苯磺酸氨氯地平颗粒广东东阳光药业股份有限公司2.2CXHS2400125苯磺酸氨氯地平颗粒广东东阳光药业股份有限公司2.2CXHS2400124苯磺酸氨氯地平颗粒广东东阳光药业股份有限公司2.2CXHS2400123苯磺酸氨氯地平颗粒广东东阳光药业股份有限公司2.2CXHS2400122苯磺酸氨氯地平颗粒广东东阳光药业股份有限公司2.2CXHS2400121甲磺酸阿美替尼片江苏豪森药业集团有限公司2.4CXHS2400127IM19嵌合抗原受体T细胞注射液(IM19 CAR-T细胞注射液)北京艺妙神州医药科技有限公司1CXSS2400131 新药临床申请药品名称企业注册分类受理号Sonrotoclax薄膜包衣片百济神州(苏州)生物科技有限公司1CXHL2401304Sonrotoclax薄膜包衣片百济神州(苏州)生物科技有限公司1CXHL2401303Sonrotoclax薄膜包衣片百济神州(苏州)生物科技有限公司1CXHL2401302Sonrotoclax薄膜包衣片百济神州(苏州)生物科技有限公司1CXHL2401301HS-10502片江苏豪森药业集团有限公司1CXHL2401300HS-10502片江苏豪森药业集团有限公司1CXHL2401299F1F3软膏中奥生物医药技术(广东)有限公司1CXHL2401296F1F3软膏中奥生物医药技术(广东)有限公司1CXHL2401295INV-6452片广东省创新药转化医学研究院有限公司1CXHL2401293INV-6452片广东省创新药转化医学研究院有限公司1CXHL2401292TYK-00540片浙江同源康医药股份有限公司1CXHL2401284TYK-00540片浙江同源康医药股份有限公司1CXHL2401283HPB-143片杭州多域生物技术有限公司1CXHL2401282HPB-143片杭州多域生物技术有限公司1CXHL2401281XH-S004片浙江星浩澎博医药有限公司1CXHL2401279XH-S004片浙江星浩澎博医药有限公司1CXHL2401278AY-1001安域生物科技(杭州)有限公司2.1CXHL2401289AY-1001安域生物科技(杭州)有限公司2.1CXHL2401288AY-1001安域生物科技(杭州)有限公司2.1CXHL2401287AY-1001安域生物科技(杭州)有限公司2.1CXHL2401286GW901肠溶软胶囊成都国为生物医药有限公司2.1CXHL2401277利拉鲁肽注射液浙江和泽医药科技股份有限公司2.2CXHL2401290ZL2301广东众丽医药科技有限公司2.2CXHL2401280注射用JP-1366丽珠医药集团股份有限公司2.2;2.4CXHL2401291泽布替尼胶囊百济神州(苏州)生物科技有限公司2.4CXHL2401298泽布替尼胶囊百济神州(苏州)生物科技有限公司2.4CXHL2401297天麻素注射液昆药集团股份有限公司2.4CXHL2401294西达本胺片深圳微芯生物科技股份有限公司2.4CXHL2401285吸附无细胞百(三组分)白破b型流感嗜血杆菌(结合)-ACYW135群脑膜炎球菌(结合)联合疫苗康希诺生物股份公司1.4CXSL2400797KYS202002A注射液江苏康缘药业股份有限公司1CXSL2400808NKC007细胞注射液广州蒽恺赛生物科技有限公司1CXSL2400809LYN101注射液上海才致药成生物科技有限公司1CXSL2400810ESG206注射液上海诗健生物科技有限公司1CXSL2400807CM313(SC)注射液康诺亚生物医药科技(成都)有限公司1CXSL2400804GenSci120注射液长春金赛药业有限责任公司1CXSL2400803CM313(SC)注射液康诺亚生物医药科技(成都)有限公司1CXSL2400802SCT650C 注射液神州细胞工程有限公司1CXSL2400801夫那奇珠单抗注射液苏州盛迪亚生物医药有限公司2.2CXSL2400806夫那奇珠单抗注射液苏州盛迪亚生物医药有限公司2.2CXSL2400805注射用BAT1006百奥泰生物制药股份有限公司2.4CXSL2400798 仿制药申请药品名称企业注册分类受理号铝碳酸镁混悬液合肥远志医药科技开发有限公司3CYHS2404126盐酸美金刚口腔崩解片重庆苯立方医药科技有限公司3CYHS2404125碳酸镧颗粒海南皇隆制药股份有限公司3CYHS2404124马来酸依那普利口服溶液北京海一药业有限公司3CYHS2404123酮咯酸氨丁三醇注射液广东南国药业有限公司3CYHS2404122对乙酰氨基酚颗粒上海上药信谊药厂有限公司3CYHS2404121复合磷酸氢钾注射液辰欣药业股份有限公司3CYHS2404107盐酸溴己新注射液西安达莫制药有限公司3CYHS2404084维生素K1注射液成都苑东生物制药股份有限公司3CYHS2404082酮康唑乳膏丽彩甘肃西峰制药有限公司3CYHS2404101酮康唑乳膏丽彩甘肃西峰制药有限公司3CYHS2404100美洛昔康纳米晶注射液健康元药业集团股份有限公司3CYHS2404070硫酸吗啡盐酸纳曲酮缓释胶囊成都苑东生物制药股份有限公司3CYHS2404077硫酸吗啡盐酸纳曲酮缓释胶囊成都苑东生物制药股份有限公司3CYHS2404075帕米膦酸二钠注射液河北汇德旭盛医药科技有限公司3CYHS2404061贝那普利氢氯噻嗪片广东万泰科创药业有限公司3CYHS2404056布美他尼注射液江苏迪赛诺制药有限公司3CYHS2404055布美他尼注射液江苏迪赛诺制药有限公司3CYHS2404054米诺地尔搽剂合肥远志医药科技开发有限公司3CYHS2404057左氧氟沙星注射液江苏长江药业有限公司3CYHS2404048硫辛酸片北京双鹭药业股份有限公司3CYHS2404041枸橼酸西地那非片河北常山生化药业股份有限公司4CYHS2404130枸橼酸西地那非片河北常山生化药业股份有限公司4CYHS2404129氯沙坦钾氢氯噻嗪片裕松源药业有限公司4CYHS2404128替米沙坦氨氯地平片苏州中化药品工业有限公司4CYHS2404127卡左双多巴缓释片海南慧通生物医药科技有限公司4CYHS2404120硫酸镁钠钾口服用浓溶液山东新华制药股份有限公司4CYHS2404119米库氯铵注射液珠海优润医药科技有限公司4CYHS2404117米库氯铵注射液珠海优润医药科技有限公司4CYHS2404116利格列汀二甲双胍片(II)华润赛科药业有限责任公司4CYHS2404115他达拉非片以岭万洲国际制药有限公司4CYHS2404114蒙脱石散健民药业集团股份有限公司4CYHS2404113注射用硫酸艾沙康唑海口市制药厂有限公司4CYHS2404112地夸磷索钠滴眼液苏州乐珠制药有限公司4CYHS2404110氯雷他定糖浆江苏万高药业股份有限公司4CYHS2404109盐酸乌拉地尔注射液江苏开元药业有限公司4CYHS2404108注射用头孢唑肟钠/氯化钠注射液湖南科伦制药有限公司4CYHS2404106氧(液态)珠海盈德气体有限公司4CYHS2404105卡贝缩宫素注射液常州四药制药有限公司4CYHS2404104依折麦布阿托伐他汀钙片(I)浙江花园药业有限公司4CYHS2404111磷/碳酸氢钠血滤置换液宁波泰瑞斯科技有限公司4CYHS2404099地屈孕酮片浙江恒研医药科技有限公司4CYHS2404098马来酸非尼拉敏盐酸萘甲唑啉滴眼液广州仁恒医药科技股份有限公司4CYHS2404097富马酸伏诺拉生片吉林天衡药业有限公司4CYHS2404096富马酸伏诺拉生片吉林天衡药业有限公司4CYHS2404095富马酸伏诺拉生片天津武田药品有限公司4CYHS2404094盐酸尼卡地平注射液山东现代医药科技有限公司4CYHS2404093甲磺酸倍他司汀片哈尔滨三联药业股份有限公司4CYHS2404092硫酸艾沙康唑胶囊重庆希韦医药科技有限公司4CYHS2404091富马酸二甲酯肠溶胶囊厦门力卓药业有限公司4CYHS2404090蛋白琥珀酸铁口服溶液圣嘉(滨海)生物医药科技有限公司4CYHS2404089沙库巴曲缬沙坦钠片华中药业股份有限公司4CYHS2404088沙库巴曲缬沙坦钠片华中药业股份有限公司4CYHS2404087沙库巴曲缬沙坦钠片华中药业股份有限公司4CYHS2404086硫酸氢氯吡格雷片浙江众延医药科技有限公司4CYHS2404085硫酸氨基葡萄糖胶囊四川新斯顿制药股份有限公司4CYHS2404083盐酸伊托必利片裕松源药业有限公司4CYHS2404103硫酸氨基葡萄糖胶囊海南海力制药有限公司4CYHS2404102氧哈尔滨翼龙工业气体有限公司4CYHS2404074盐酸奥布卡因滴眼液齐鲁制药有限公司4CYHS2404073美阿沙坦钾片广州市联瑞制药有限公司4CYHS2404072美阿沙坦钾片广州市联瑞制药有限公司4CYHS2404071利多卡因凝胶贴膏北京百奥药业有限责任公司4CYHS2404069盐酸曲唑酮缓释片江苏万高药业股份有限公司4CYHS2404068盐酸曲唑酮缓释片江苏万高药业股份有限公司4CYHS2404067罗库溴铵注射液云南药科院生物医药股份有限公司4CYHS2404081枸橼酸西地那非口腔崩解片烟台鲁银药业有限公司4CYHS2404080硫酸氢氯吡格雷片辽宁鑫善源药业有限公司4CYHS2404079氧液化空气(浙江)有限公司4CYHS2404078醋酸去氨加压素片江苏利泰尔药业有限公司4CYHS2404076阿戈美拉汀片苏州第三制药厂有限责任公司4CYHS2404062注射用磷酸特地唑胺湖南赛隆药业有限公司4CYHS2404060巴氯芬片合肥英太制药有限公司4CYHS2404059氧蒲城县凯利液化气有限责任公司4CYHS2404058瑞舒伐他汀依折麦布片(I)浙江昂利康制药股份有限公司4CYHS2404053苯磺酸左氨氯地平片广东万泰科创药业有限公司4CYHS2404052苯磺酸左氨氯地平片广东万泰科创药业有限公司4CYHS2404051美阿沙坦钾片海南赛立克药业有限公司4CYHS2404066美阿沙坦钾片海南赛立克药业有限公司4CYHS2404065枸橼酸西地那非口腔崩解片浙江莎普爱思药业股份有限公司4CYHS2404064硫酸镁钠钾口服用浓溶液江西博泰药业有限公司4CYHS2404063奥美沙坦酯氨氯地平片裕松源药业有限公司4CYHS2404050氨甲环酸片石家庄四药有限公司4CYHS2404049硫酸镁钠钾口服用浓溶液山东朗诺制药有限公司4CYHS2404046苯磺酸美洛加巴林片齐鲁制药(海南)有限公司4CYHS2404045苯磺酸美洛加巴林片齐鲁制药(海南)有限公司4CYHS2404044米库氯铵注射液湖南埃威格林医药科技有限公司4CYHS2404043米库氯铵注射液湖南埃威格林医药科技有限公司4CYHS2404042硫酸氨基葡萄糖胶囊广州博济生物医药科技园有限公司4CYHS2404047乌司奴单抗注射液石药集团巨石生物制药有限公司3.3CXSS2400130吲哚美辛凝胶贴膏深圳珐玛易药品科技有限公司3CYHL2400238利多卡因丙胺卡因气雾剂北京中泰邦医药科技有限公司3CYHL2400237氟比洛芬凝胶贴膏江苏万高药业股份有限公司4CYHL2400236人纤维蛋白原郑州莱士血液制品有限公司3.4CXSL2400799人纤维蛋白原郑州莱士血液制品有限公司3.4CXSL2400800 进口申请药品名称企业注册分类受理号盐酸阿曲生坦片Novartis Pharma Schweiz AG1JXHS2400103古塞奇尤单抗注射液Janssen-Cilag International NV2.2JXSS2400104美沙拉秦肠溶缓释胶囊Zydus Lifesciences Limited5.2JYHS2400058镥[177Lu]Lu-NeoB注射液Novartis Pharma AG1JXHL2400281用于制备放射性药物[68Ga]Ga-NeoB注射液的药盒Novartis Pharma AG1JXHL2400280注射用JX10Corxel Pharmaceuticals, Inc.1JXHL2400279BAY 2927088片Bayer AG1JXHL2400275BAY 2927088片Bayer AG1JXHL2400274Fosmanogepix注射液Basilea Pharmaceutica International Ltd, Allschwil1JXHL2400273Fosmanogepix片Basilea Pharmaceutica International Ltd, Allschwil1JXHL2400272Fosmanogepix片Basilea Pharmaceutica International Ltd, Allschwil1JXHL2400271DS-3201b片Daiichi Sankyo, Inc.2.4JXHL2400278DS-3201b片Daiichi Sankyo, Inc.2.4JXHL2400277DS-3201b片Daiichi Sankyo, Inc.2.4JXHL2400276DS-1062aDaiichi Sankyo, Inc.1JXSL2400231Riliprubart注射液Sanofi-aventis Recherche & Developpement1JXSL2400228注射用戈沙妥珠单抗Gilead Sciences, Inc.2.2JXSL2400229Eflapegrastim注射液Hanmi Pharm. Co., Ltd.3.1JXSL2400230 中药相关申请药品名称企业注册分类受理号枇杷清肺颗粒河北万岁药业有限公司3.1CXZS2400036桃红四物颗粒河北万邦复临药业有限公司3.1CXZS2400035星蒌承气颗粒山西振东制药股份有限公司1.1CXZL2400080 注：绿色字体部分为潜在首仿品种；不包含原料药、医用氧、注射用水、氯化钠或葡萄糖注射液等申请，不包含再注册、一次性进口、技术转移、复审申请。

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