64Cu-GRIP B(64Cu-GRIP B) - 在研适应症：非霍奇金淋巴瘤_专利_临床

概要

基本信息

药物类型

多肽偶联核素、诊断用放射药物

别名

64Cu-labeled GRIP B、Copper-64 labeled Granzyme B

靶点-

作用机制

PET imaging(正电子发射断层成像术增强剂)

治疗领域

肿瘤免疫系统疾病血液及淋巴系统疾病

在研适应症

非霍奇金淋巴瘤

非在研适应症-

原研机构-

在研机构

The University of California, San Francisco

The V Foundation

非在研机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

使用我们的ADC技术数据为新药研发加速。

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关联

3

项与 64Cu-GRIP B 相关的临床试验

NCT06522932 / Recruiting临床1期IIT

A Phase I/Ib PET Imaging Study of 64Cu-GRIP B, a Radiotracer Targeting Granzyme B, in Patients Receiving CD19-directed CAR-T Therapy

This is a phase I/Ib imaging study of granzyme B, 64-copper granzyme targeting restricted interaction peptide specific to family member B (64Cu-GRIP B) Positron Emission Tomography (PET) in patients with relapsed/refractory non-Hodgkin's lymphoma (NHL) receiving CD19-directed Chimeric antigen receptor T cells (CAR-T) therapy. The proposed study represents the first-ever lymphoma patient imaging studies with 64Cu-GRIP B PET. The tracer is designed to detect extracellular granzyme B as it is secreted by activated immune cells in the tumor microenvironment, which may highlight tumors that will exhibit a durable response to Cluster of Differentiation 19 (CD19)-directed CAR T-cell therapy.

开始日期2024-10-30

申办/合作机构

The University of California, San Francisco

[+1]

NCT05888532 / Recruiting临床1/2期IIT

A First-in-Human, Phase I/II PET Imaging Study of 64Cu-GRIP B, a Radiotracer Targeting Granzyme B, in Patients With Advanced Malignancies

This phase I/II clinical trial evaluates if using a radiotracer targeting granzyme B, 64-copper granzyme targeting restricted interaction peptide specific to family member B (64 Cu-GRIP B) with positron emission tomography (PET) imaging can be safe and useful for detecting granzyme B (GrB) in patients with advanced cancers that has spread to nearby tissue or lymph nodes (advanced). Granzyme B (GrB) is a biomarker produced by immune cells in response to immunotherapy, which may highlight tumors that are more likely to respond to treatment. The study population is focused on genitourinary (GU) malignancies, including renal cell and urothelial cancer, two tumor types with high mutational burden and tumor infiltrating lymphocytes compared to other tumor types, and have a predictable response rate at the population level to immune checkpoint inhibitors. The information gained from this trial may allow researchers to develop future trials where 64Cu-GRIP B PET may serve as a biomarker to monitor early response to immunomodulatory therapies which are used to stimulate or suppress the immune system and may help the body fight cancer.

开始日期2023-05-25

申办/合作机构

The University of California, San Francisco

[+1]

NCT05906693 / CompletedN/AIIT

A Cross-sectional Study - The Quality of Life in Individuals With Parkinson's Disease: Is it Related to Functionality and Tremor Severity?

This study aimed to examine the relationship of quality of life with tremor severity and upper limb functionality in individuals with Parkinson's Disease. The differences between Parkinson's Disease Quality of Life Questionnaire, Nine-Hole Peg Test, grip and pinch strength values in the individuals with and without tremor in the study were investigated.

开始日期2019-01-01

申办/合作机构

Pamukkale University

100 项与 64Cu-GRIP B 相关的临床结果

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100 项与 64Cu-GRIP B 相关的转化医学

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100 项与 64Cu-GRIP B 相关的专利（医药）

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2

项与 64Cu-GRIP B 相关的文献（医药）

2021-10-27·ACS Central Science1区 · 化学

In Vivo Measurement of Granzyme Proteolysis from Activated Immune Cells with PET

1区 · 化学

ArticleOA

作者: Fong, Lawrence ; Evans, Michael J ; Zhao, Ning ; Looney, Mark R ; Cleary, Simon J ; Bardine, Conner ; Huang, Yangjie ; Craik, Charles S ; Lourenço, André Luiz ; Oh, David Y ; Wang, Yung-Hua ; Wilson, David M

The biology of human granzymes remains enigmatic in part due to our inability to probe their functions outside of in vitro assays or animal models with divergent granzyme species. We hypothesize that the biology of human granzymes could be better elaborated with a translational imaging technology to reveal the contexts in which granzymes are secreted and biochemically active in vivo. Here, we advance toward this goal by engineering a Granzyme targeting Restricted Interaction Peptide specific to family member B (GRIP B) to measure secreted granzyme B (GZMB) biochemistry with positron emission tomography. A proteolytic cleavage of ⁶⁴Cu-labeled GRIP B liberates a radiolabeled form of Temporin L, which sequesters the radioisotope by binding to adjacent phospholipid bilayers. Thus, at extended time points postinjection (i.e., hours, not seconds), tissue biodistribution of the radioisotope in vivo reflects relative units of the GZMB activity. As a proof of concept, we show in three syngeneic mouse cancer models that ⁶⁴Cu-GRIP B detects GZMB from T cells activated with immune checkpoint inhibitors (CPI). Remarkably, the radiotracer detects the proteolysis within tumors but also in lymphoid tissue, where immune cells are activated by a systemic CPI. Control experiments with an uncleavable analogue of ⁶⁴Cu-GRIP B and tumor imaging studies in germline GZMB knockout mice were applied to show that ⁶⁴Cu-GRIP B is specific for GZMB proteolysis. Furthermore, we explored a potential noncytotoxic function for GZMB by applying ⁶⁴Cu-GRIP B to a model of pulmonary inflammation. In summary, we demonstrate that granzyme biochemistry can be assessed in vivo using an imaging modality that can be scaled vertically into human subjects.

2018-10-15·Clinical Cancer Research1区 · 医学

CD8+ T-Cell Density Imaging with 64Cu-Labeled Cys-Diabody Informs Immunotherapy Protocols

1区 · 医学

Article

作者: Silvestrini, Matthew T. ; Wu, Anna M. ; Salazar, Felix B. ; Seo, Jai Woong ; Ingham, Elizabeth S. ; Mahakian, Lisa M. ; Ferrara, Katherine W. ; Borowsky, Alexander D. ; Tam, Sarah ; Tavaré, Richard

AbstractPurpose: Noninvasive and quantitative tracking of CD8+ T cells by PET has emerged as a potential technique to gauge response to immunotherapy. We apply an anti-CD8 cys-diabody, labeled with 64Cu, to assess the sensitivity of PET imaging of normal and diseased tissue.Experimental Design: Radiolabeling of an anti-CD8 cys-diabody (169cDb) with 64Cu was developed. The accumulation of 64Cu-169cDb was evaluated with PET/CT imaging (0, 5, and 24 hours) and biodistribution (24 hours) in wild-type mouse strains (n = 8/group studied with imaging and IHC or flow cytometry) after intravenous administration. Tumor-infiltrating CD8+ T cells in tumor-bearing mice treated with CpG and αPD-1 were quantified and mapped (n = 6–8/group studied with imaging and IHC or flow cytometry).Results: We demonstrate the ability of immunoPET to detect small differences in CD8+ T-cell distribution between mouse strains and across lymphoid tissues, including the intestinal tract of normal mice. In FVB mice bearing a syngeneic HER2-driven model of mammary adenocarcinoma (NDL), 64Cu-169cDb PET imaging accurately visualized and quantified changes in tumor-infiltrating CD8+ T cells in response to immunotherapy. A reduction in the circulation time of the imaging probe followed the development of treatment-related liver and splenic hypertrophy and provided an indication of off-target effects associated with immunotherapy protocols.Conclusions: 64Cu-169cDb imaging can spatially map the distribution of CD8+ T cells in normal organs and tumors. ImmunoPET imaging of tumor-infiltrating cytotoxic CD8+ T cells detected changes in T-cell density resulting from adjuvant and checkpoint immunotherapy protocols in our preclinical evaluation. Clin Cancer Res; 24(20); 4976–87. ©2018 AACR.

100 项与 64Cu-GRIP B 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
非霍奇金淋巴瘤	临床1期	美国	The University of California, San Francisco	2024-10-30
非霍奇金淋巴瘤	临床1期	美国	The V Foundation	2024-10-30