Immune-Onc靶向LILRB2(ILT4)全新抑制性抗体IO-108获FDA批准将在晚期实体瘤中开展人体临床试验

2021-08-13 JACKZHAO MedSci原创

2021年8月12日 - 处于临床阶段、致力于开发靶向免疫抑制性髓细胞免疫检查点创新癌症免疫疗法的生物制药公司——Immune-Onc Therapeutics, Inc.(简

免疫疗法药物Nivolumab治疗晚期癌症患者具有良好的5年生存率

8月12日,以明生物(Immune-Onc Therapeutics)宣布,其引研发的IO-108用于治疗实体瘤的I期临床试验申请已获美国FDA批准通过。IO-108是一种靶向白细胞免疫球蛋白样受体B2(LILRB2,又称ILT4)的全新抑制性抗体。

LILRB2,又称ILT4,主要在髓系细胞上表达,包括单核细胞、树突状细胞、巨噬细胞和嗜中性粒细胞。在实体瘤中,LILRB2 可以与肿瘤微环境(TME)中的相关配体 HLA-G、ANGPTLs、SEMA4A和CD1d 相互作用,致使髓系细胞促肿瘤(容许或促进肿瘤生长),增进肿瘤免疫逃逸。LILRB 家族还包括 LILRB4(也称为 ILT3)和 LAIR1,都具有不同的表达模式和不同的功能。

以明生物在2020年癌症免疫治疗学会(Society for Immunotherapy of Cancer)年会上发表的临床前数据1表明,IO-108具有髓细胞免疫检查点抑制剂的功效。IO-108可对免疫抑制性髓系细胞重新编程,使其表现出促炎表型,从而增强固有和适应性免疫系统的抗肿瘤免疫反应。

以明生物是一家处于临床阶段、致力于开发靶向免疫抑制性髓细胞免疫检查点创新癌症免疫疗法的生物制药公司,专注于癌症免疫治疗,致力于为癌症患者寻找并开发全新的髓细胞免疫检查点抑制剂。该公司的目标是通过转化对髓系细胞生物学和免疫抑制性受体独到的科学见解,发现并开发可以在肿瘤微环境中解除免疫抑制的首创生物新药。
图片以明生物首席执行官廖晓伶博士

以明生物首席执行官廖晓伶博士表示,“IO-108的IND申请获批,是以明生物在推进靶向免疫抑制性受体LILRB家族的、全新髓细胞免疫检查点抑制剂产品管线的过程中,取得的又一重大里程碑。我们深受IO-108优异临床前数据鼓舞,并很欣慰我们在LILRB生物学和转化科学领域中的深耕使得该产品进入临床成为可能。我们期待临床试验的启动,从而进一步了解LILRB在癌症中的作用,并评估IO-108在晚期实体瘤患者中的治疗潜力。”

IO-108的Ⅰ期多中心剂量递增临床研究将由一个单药治疗队列和一个联合治疗队列组成,旨在评估IO-108单药疗法以及IO-108和PD-1阻断性抗体帕博利珠单抗联用的安全性、耐受性、药代动力学和药效动力学。研究将对生物标志物进行评估,以便从机制角度理解临床数据,为后续试验提供指导。这项研究还将为确认初步疗效信号提供可能。在确定II期推荐剂量后,以明生物计划在特定适应症扩展队列中评估IO-108和PD-1阻断性抗体联用以及IO-108单药治疗的疗效、安全性和耐受性。

IO-108可以以高亲和力和特异性结合LILRB2,并阻断LILRB2在肿瘤微环境中与癌症免疫抑制相关的配体HLA-G、ANGPTLs、SEMA4A和CD1d的相互作用。在临床前研究中,用IO-108处理含髓系细胞的多种人源原代免疫细胞系统,可以增强其对与抗肿瘤免疫相关的多种刺激的促炎反应。作为单药,IO-108可以逆转髓系细胞由于被“肿瘤调节”而导致的抗炎表型,并促进单核细胞分化成促炎性的树突状细胞。不仅如此,IO-108还可以增强PD-1阻断性抗体对CD4+T细胞在与异体巨噬细胞共培养时的激活作用。在小鼠模型中,IO-108可以抑制实体瘤生长,并增强T细胞反应。这些数据共同表明,IO-108与标准免疫疗法和/或其它促免疫生成的疗法联用,在治疗无论是对T细胞检查点抑制剂耐药还是敏感的实体瘤时均具有产生累积或协同效益的潜力。

以明生物一直围绕髓细胞免疫检查点——白细胞免疫球蛋白样受体亚家族B(LILRB)开展研发工作,利用生物学平台的协同效应,已打造出多条极具潜力的产品管线。其中包括两款处于I期临床开发阶段的全球首创新药:针对实体瘤的IO-108,以及治疗急性髓系白血病(AML)和慢性粒-单核细胞白血病(CMML)、靶向LILRB4(又称ILT3)的IO-202。公司同时还在积极计划IO-202在实体瘤中的疗效评估。2020年10月,美国食品药品监督管理局(FDA)授予IO-202孤儿药资格认定。此外,公司产品管线还包括一款靶向LAIR1的抗体新药IO-106,以及多个未公开的针对实体瘤和恶性血液瘤的项目。

以明生物与美国德克萨斯大学(The University of Texas),阿尔伯特·爱因斯坦医学院(Albert Einstein College of Medicine)和纪念斯隆·凯特琳癌症中心(Memorial Sloan Kettering Cancer Center)等机构结成了长期的战略研究合作关系,并已建立一系列专有的实验模型、方法和工具进行生物学探究,将前沿研究转化为对创新疗法的开发。以明生物总部位于加利福尼亚州帕洛阿托,现已组建了一支在药物开发领域经验丰富,具有全球顶尖生物科技公司深厚资历的多元化团队。

参考资料:

1. www.immune-onc.com/pr-posts/immune-onc-therapeutics-to-present-preclinical-data-for-io-108-a-novel-antagonist-antibody-targeting-lilrb2-ilt4-in-solid-tumors-at-sitc-2020

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    2021-12-05 bugit
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    2021-08-15 quxin068
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    2021-08-13 ms8000000769309498

    学习了

    0

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    2021-08-13 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

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