DEVELOP A NONCOMPETITIVE MONOCLONAL ANTI-CD25
DEVELOP A NONCOMPETITIVE MONOCLONAL ANTI-CD25
批准号:
10291511
负责人:
ETHAN DMITROVSKY
金额:
$5.41万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
未结题
起止时间:
2020-09-25 至 2025-09-24
关键词:
AnimalsAntibodiesCellsEnvironmentExposure toHumanIL2RA geneImmune TargetingImmune responseIntravenousLightRegulatory T-LymphocyteSurfaceSurgical ReplantationTestingTumor Antibodiesantibody conjugatecell typeimage guided therapyimaging programmolecular imagingnovel diagnosticsphase III trialphotoimmunotherapypreventprogramsresponsetumor
中文摘要
NCI 分子成像计划 (MIP) 开发新的诊断和图像引导疗法。 MIP 最令人兴奋的项目之一是光免疫疗法 (PIT),其中通过静脉注射与特殊光吸收剂 (IR700) 结合的抗体。抗体缀合物在肿瘤中积聚,随后近红外光谱中的光照射导致快速杀死肿瘤。 PIT 的初步人体测试正在进行第三阶段试验,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缀合物来增强 PIT 的反应,这些抗体缀合物针对肿瘤周围常见的免疫抑制环境。 具体来说,通常存在称为 T 调节细胞的细胞类型。 该细胞在其表面表达 CD25。 在动物研究中,暴露于近红外光下的抗肿瘤抗体缀合物和抗 CD25 抗体缀合物的组合不仅可以杀死暴露的肿瘤,还可以杀死未受光照射的肿瘤,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,开发针对 Tregs 的抗 CD25 抗体是该项目的首要任务。
英文摘要
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.
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