DEVELOP A NONCOMPETITIVE MONOCLONAL ANTI-CD25

开发非竞争性单克隆抗 CD25

• 批准号: 10377880
• 负责人: ETHAN DMITROVSKY
• 金额: $ 3.03万
• 依托单位: LEIDOS BIOMEDICAL RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-25 至 2025-09-24
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10377880
• 关键词: Animals; Antibodies; Cells; Environment; Exposure to; Human; IL2RA gene; Immune Targeting; Immune response; Intravenous; Light; Regulatory T-Lymphocyte; Surface; Surgical Replantation; Testing; Tumor Antibodies; antibody conjugate; cell type; image guided therapy; imaging program; molecular imaging; novel diagnostics; phase III trial; photoimmunotherapy; prevent; programs; response; tumor

The NCI Molecular Imaging Program (MIP) develops new diagnostics and image guided therapies. One of the most exciting projects from the MIP is Photoimmunotherapy (PIT) in which an antibody conjugated to a special photoabsorber (IR700) is injected intravenously. The antibody conjugate accumulates in the tumor and subsequent light exposure in the near infrared spectrum results in rapid tumor killing. The initial human testing of PIT is in Phase 3 trials and will likely be approved in the US within 2 years. We have been working to augment the response of PIT by adding additional antibody conjugates that target the immune suppressive environment often found around tumors. Specifically, a cell type known as a T-regulatory cell is often present. This cell expresses CD25 on its surface. In animal studies the combination of an anti-tumor antibody conjugate and anti CD25 antibody conjugate exposed to near infrared light resulted not only in killing of the exposed tumors but also killed tumors that were not irradiated with light AND prevented reimplantation of the tumor a month after therapy. This implies a strong immune response. Thus, developing an antiCD25 antibody to target Tregs is a high priority for the program.

NCI分子成像计划（MIP）开发新的诊断和图像引导治疗。 MIP最令人兴奋的项目之一是光免疫疗法（PIT），其中静脉注射与特殊光吸收剂（IR 700）结合的抗体。抗体偶联物在肿瘤中积累，随后在近红外光谱中的光暴露导致快速的肿瘤杀伤。 PIT的初步人体试验正在进行3期试验，可能会在2年内在美国获得批准。我们一直致力于通过添加额外的抗体偶联物来增强PIT的反应，这些抗体偶联物靶向肿瘤周围常见的免疫抑制环境。 具体地，通常存在称为T调节细胞的细胞类型。 该细胞在其表面上表达CD25。 在动物研究中，暴露于近红外光的抗肿瘤抗体偶联物和抗CD25抗体偶联物的组合不仅杀死暴露的肿瘤，而且杀死未用光照射的肿瘤，并防止治疗后一个月肿瘤的再植入。 这意味着强烈的免疫反应。因此，开发一种靶向T细胞的抗CD25抗体是该计划的优先事项。