Biond Biologics, Misgav, Israel
Biond Biologics, Misgav, Israel.
J Immunother Cancer. 2022 Sep;10(9). doi: 10.1136/jitc-2022-004859.
Cancer immunotherapy has revolutionized cancer treatment. However, considering the limited success of immunotherapy to only some cancer types and patient cohorts, there is an unmet need for developing new treatments that will result in higher response rates in patients with cancer. Immunoglobulin-like transcript 2 (ILT2), a LILRB family member, is an inhibitory receptor expressed on a variety of immune cells including T cells, natural killer (NK) cells and different myeloid cells. In the tumor microenvironment, binding of class I MHC (in particular HLA-G) to ILT2 on immune cells mediates a strong inhibitory effect, which manifests in inhibition of antitumor cytotoxicity of T and NK cells, and prevention of phagocytosis of the tumor cells by macrophages.
We describe here the development and characteristics of BND-22, a novel, humanized monoclonal antibody that selectively binds to ILT2 and blocks its interaction with classical MHC I and HLA-G. BND-22 was evaluated for its binding and blocking characteristics as well as its ability to increase the antitumor activity of macrophages, T cells and NK cells in various in vitro, ex vivo and in vivo systems.
Collectively, our data suggest that BND-22 enhances activity of both innate and adaptive immune cells, thus generating robust and comprehensive antitumor immunity. In humanized mice models, blocking ILT2 with BND-22 decreased the growth of human tumors, hindered metastatic spread to the lungs, and prolonged survival of the tumor-bearing mice. In addition, BND-22 improved the antitumor immune response of approved therapies such as anti-PD-1 or anti-EGFR antibodies.
BND-22 is a first-in-human ILT2 blocking antibody which has demonstrated efficient antitumor activity in various preclinical models as well as a favorable safety profile. Clinical evaluation of BND-22 as a monotherapy or in combination with other therapeutics is under way in patients with cancer.
NCT04717375.
癌症免疫疗法已经彻底改变了癌症的治疗方式。然而，鉴于免疫疗法仅对某些癌症类型和患者群体有效，因此需要开发新的治疗方法，以提高癌症患者的反应率。免疫球蛋白样转录物 2（ILT2）是 LILRB 家族的成员，是一种在多种免疫细胞上表达的抑制性受体，包括 T 细胞、自然杀伤（NK）细胞和不同的髓样细胞。在肿瘤微环境中，类 I MHC（特别是 HLA-G）与免疫细胞上的 ILT2 结合，介导强烈的抑制作用，表现为抑制 T 和 NK 细胞的抗肿瘤细胞毒性，并防止巨噬细胞吞噬肿瘤细胞。
我们在这里描述了 BND-22 的开发和特性，BND-22 是一种新型的人源化单克隆抗体，选择性地与 ILT2 结合并阻断其与经典 MHC I 和 HLA-G 的相互作用。评估了 BND-22 的结合和阻断特性以及其在各种体外、离体和体内系统中增强巨噬细胞、T 细胞和 NK 细胞抗肿瘤活性的能力。
总的来说，我们的数据表明，BND-22 增强了固有和适应性免疫细胞的活性，从而产生了强大而全面的抗肿瘤免疫。在人源化小鼠模型中，用 BND-22 阻断 ILT2 可减少人肿瘤的生长，阻碍肿瘤向肺部转移，并延长荷瘤小鼠的存活时间。此外，BND-22 改善了批准的治疗方法（如抗 PD-1 或抗 EGFR 抗体）的抗肿瘤免疫反应。
BND-22 是一种人源化的 ILT2 阻断抗体，在各种临床前模型中表现出有效的抗肿瘤活性，并具有良好的安全性。BND-22 作为单药或与其他疗法联合治疗癌症患者的临床评估正在进行中。
NCT04717375。
