DEVELOP A NONCOMPETITIVE MONOCLONAL ANTI-CD25
DEVELOP A NONCOMPETITIVE MONOCLONAL ANTI-CD25
批准号:
10377880
负责人:
ETHAN DMITROVSKY
金额:
$3.03万
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),即静脉注射连接到特殊光吸收剂(IR700)的抗体。抗体结合物在肿瘤中积聚,随后在近红外光谱中照射会导致肿瘤的快速杀灭。PIT的初步人体试验处于第三阶段试验,很可能在两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结合物来增强PIT的反应,这些抗体结合物针对肿瘤周围经常发现的免疫抑制环境。具体地说,通常存在一种称为T调节细胞的细胞类型。这个细胞在其表面表达CD25。在动物实验中,抗肿瘤抗体结合物和抗CD25抗体结合物联合暴露在近红外光下,不仅可以杀死暴露的肿瘤,而且可以杀死未经光照射的肿瘤,并防止肿瘤在治疗后一个月内再次种植。这意味着有很强的免疫反应。因此,开发针对Tregs的抗CD25抗体是该计划的高度优先事项。
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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