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    PROSPECTIVE IDENTIFICATION AND CHARACTERIZATION OF BREAST CANCER STEM CELLS
    82.
    发明申请
    PROSPECTIVE IDENTIFICATION AND CHARACTERIZATION OF BREAST CANCER STEM CELLS 审中-公开
    乳腺癌干细胞的前瞻性鉴定和表征

    公开(公告)号：WO2003050502A2

    公开(公告)日：2003-06-19

    申请号：PCT/US2002/039191

    申请日：2002-12-06

    Applicant: REGENTS OF THE UNIVERSITY OF MICHIGAN ,  CLARKE, Michael, F. ,  WICHA, Max, S. ,  AL-HAJJ, Mohammad

    Inventor： CLARKE, Michael, F. ,  WICHA, Max, S. ,  AL-HAJJ, Mohammad

    IPC: G01N

    CPC classification number: C07K16/28 ,  A61K38/1703 ,  A61K47/6897 ,  A61K47/6901 ,  A61K2039/505 ,  B82Y5/00 ,  C07K16/3015 ,  C12N5/0695

    Abstract: Human breast tumors contain heterogeneous cancer cells. Using an animal xenograft model in which human breast cancer cells were grown in immunocompromised mice, we found that only a small minority of breast cancer cells had the capacity to form new tumors. The ability to form new tumors was not a stochastic property, rather certain populations of cancer cells were depleted for the ability to form new tumors, while other populations were enriched for the ability to form new tumors. Tumorigenic cells could be distinguished from non-tumorigenic cancer cells based on surface marker expression. We prospectively identified and isolated the tumorigenic cells as CD44 + CD24 -/lo LINEAGE - . As few as 100 cells from this population were able to form tumors the animal xenograft model, while tens of thousands of cells from non-tumorigenic populations failed to form tumors. The tumorigenic cells could be serially passaged, each time generating new tumors containing an expanded numbers of CD44 + CD24 -/low Lineage?- ¿tumorigenic cells as well as phenotypically mixed populations of non-tumorigenic cancer cells. This is reminiscentof the ability of normal stem cells to self-renew and differentiate. The expression of potential therapeutic targets also differed between the tumorigenic and non-tumorigenic populations. Notch activation promoted the survival of the tumorigenic cells, and a blocking antibody against Notch4 induced tumorigenic breast cancer cells to undergo apoptosis.

    Abstract translation: 人乳腺肿瘤包含异质癌细胞。 使用动物异种移植模型，其中人乳腺癌细胞在免疫受损小鼠中生长，我们发现只有少数乳腺癌细胞具有形成新肿瘤的能力。 形成新肿瘤的能力不是随机性质，而是癌细胞的某些群体耗尽形成新肿瘤的能力，而其他群体则富集形成新肿瘤的能力。 基于表面标志物表达，致瘤细胞可以与非致瘤性癌细胞区分开。 我们前瞻性地将致瘤细胞鉴定并分离为CD44 + CD24 < - / lo> LINEAGE - 。 来自该群体的少至100个细胞能够形成肿瘤动物异种移植模型，而来自非致瘤基因群的数万个细胞未能形成肿瘤。 致瘤细胞可以连续传代，每次产生含有扩增数量的CD44 + CD24 - / low> Lineage - 致瘤细胞的新肿瘤以及非致瘤性癌细胞的表型混合群体。 这让人想起正常干细胞自我更新和分化的能力。 潜在的治疗靶点的表达也在致瘤性和非致瘤性群体之间不同。 Notch活化促进致瘤细胞的存活，并且阻断Notch4诱导的致瘤性乳腺癌细胞进行细胞凋亡的抗体。

    DRUG DELIVERY SYSTEM WITH TWO-STEP TARGETING
    86.
    发明申请
    DRUG DELIVERY SYSTEM WITH TWO-STEP TARGETING 审中-公开
    具有两步瞄准的药物输送系统

    公开(公告)号：WO99029302A1

    公开(公告)日：1999-06-17

    申请号：PCT/SE1998/002231

    申请日：1998-12-04

    IPC: A61K9/00 ,  A61K9/127 ,  A61K41/00 ,  A61K47/48 ,  A61K51/00 ,  A61P35/00 ,  A61K39/44 ,  A61K51/12

    CPC classification number: B82Y5/00 ,  A61K9/1271 ,  A61K41/009 ,  A61K41/0095 ,  A61K47/6897

    Abstract: The present invention relates to a drug delivery system with two-step targeting, which comprises a combination: (a) a lipid carrier provided with cell targeting agent(s) to target the drug delivery system to specific cells or tissues; and (b) a drug enclosed in said lipid carrier and provided with a DNA targeting agent to target the drug to the nuclei of specific target cells. Furthermore, the invention relates to a method of cancer therapy in which the above drug delivery system is administered to a cancer patient. The goal is to treat or analyse both large tumour masses as well as small tumour cell clusters and single spread tumour cells. According to the invention, drug uptake in tumours will be markedly increased at the same time as the interaction of the drug with healthy organs and tissues can be minimized. The invention gives potential to convert palliative into curative treatment.

    Abstract translation: 本发明涉及具有两步靶向的药物递送系统，其包含以下组合：（a）提供有细胞靶向剂的脂质载体，以将药物递送系统靶向特定细胞或组织; 和（b）封装在所述脂质载体中并提供有DNA靶向剂以将药物靶向特定靶细胞的核的药物。 此外，本发明涉及一种癌症治疗方法，其中向癌症患者施用上述药物递送系统。 目的是治疗或分析大肿瘤块以及小肿瘤细胞簇和单细胞肿瘤细胞。 根据本发明，在药物与健康器官和组织的相互作用可以最小化的同时，肿瘤中的药物摄取将显着增加。 本发明有助于将姑息治疗转化为治疗性治疗。

    IMPROVED DETECTION AND THERAPY OF LESIONS WITH BIOTIN/AVIDIN CONJUGATES
    87.
    发明申请
    IMPROVED DETECTION AND THERAPY OF LESIONS WITH BIOTIN/AVIDIN CONJUGATES 审中-公开
    改进的生物素/抗原结合蛋白的检测和治疗

    公开(公告)号：WO1994004702A2

    公开(公告)日：1994-03-03

    申请号：PCT/US1993007754

    申请日：1993-08-20

    Applicant: IMMUNOMEDICS, INC.

    Inventor： IMMUNOMEDICS, INC. ,  GOLDENBERG, David, M.

    IPC: C12Q0

    CPC classification number: B82Y5/00 ,  A61K47/6893 ,  A61K47/6897 ,  A61K49/16 ,  A61K51/10 ,  A61K51/1018 ,  A61K51/1093 ,  A61K2123/00 ,  G01N33/534 ,  G01R33/5601

    Abstract: Uses of compositions in methods for detecting and/or treating targeted lesions in a patient are provided. The compositions used are comprised of a targeting composition comprising a biotin and targeting protein conjugate or an avidin and targeting protein conjugate; optionally, a clearing composition comprised of avidin, when the targeting composition is a biotin conjugate, or biotin, when the targeting composition is an avidin conjugate; a detection or therapeutic composition comprised of a conjugate of avidin or biotin with a targeting protein and detection or therapeutic agent; and, optionally, another detection or therapeutic composition comprised of avidin or biotin conjugated to a detection or therapeutic agent. The compositions, methods of use, and kits for use are also provided.

    Abstract translation: 提供了用于检测和/或治疗患者中靶向病变的方法中组合物的用途。 使用的组合物包含靶向组合物，其包含生物素和靶向蛋白质缀合物或抗生物素蛋白和靶向蛋白质缀合物; 任选地，当靶向组合物是抗生物素蛋白缀合物时，当靶向组合物是生物素缀合物或生物素时，由抗生物素蛋白组成的清除组合物; 由抗生物素蛋白或生物素与靶向蛋白和检测或治疗剂的缀合物组成的检测或治疗组合物; 和任选地，由与检测或治疗剂缀合的抗生物素蛋白或生物素组成的另一种检测或治疗组合物。 还提供了组合物，使用方法和使用试剂盒。

    RADIOLIGANDS FOR PRETARGETED PET IMAGING AND METHODS OF THEIR THERAPEUTIC USE
    89.
    发明申请
    RADIOLIGANDS FOR PRETARGETED PET IMAGING AND METHODS OF THEIR THERAPEUTIC USE 审中-公开
    用于预处理PET成像的放射性物质及其治疗方法

    公开(公告)号：WO2016182804A1

    公开(公告)日：2016-11-17

    申请号：PCT/US2016/030657

    申请日：2016-05-04

    Applicant: MEMORIAL SLOAN KETTERING CANCER CENTER

    Inventor： ZEGLIS, Brian ,  LEWIS, Jason ,  REINER, Thomas ,  HOUGHTON, Jacob Lee ,  MEYER, Jan-Philip ,  BRAND, Christian

    IPC: A61K51/00 ,  A61K47/48 ,  A61K51/04

    CPC classification number: A61K51/0482 ,  A61K47/6897 ,  A61K51/0453

    Abstract: Described herein are Tz/TCO-based pretargeting strategies using an Al[ 18 F]-NOTA-labeled tetrazine radioligand. This imaging strategy enables delineation of cancer at earlier time points compared to other imaging strategies and further decreases the radiation dose to healthy tissues compared to directly labeled antibodies. Al-based 18 F imaging of small molecules, such as tetrazine, has not been previously achieved due to the decomposition of tetrazine during radiofluorination. Radiofluorination is advantageous over other radiolabeling methods because, in addition to having a shorter half-life, 18 F is more readily available to produce and therefore integrated into hospital workflows.

    Abstract translation: 本文描述了使用Al [18 F] -NOTA-标记的四嗪放射性配体的基于Tz / TCO的预靶向策略。 与其他成像策略相比，该成像策略能够在较早的时间点描绘癌症，并且与直接标记的抗体相比，进一步降低对健康组织的辐射剂量。 由于在放射性氟化期间四嗪的分解，以前尚未实现基于Al的18F小分子如四嗪的成像。 放射性氟化优于其他放射性标记方法，因为除了具有较短的半衰期之外，18F更容易获得生产，因此被整合到医院工作流程中。

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