TOXINS TARGETED TO THE CELL MEMBRANE--DISRUPTION OF SIGNAL TRANSDUCTION

针对细胞膜的毒素——信号转导的破坏

基本信息

  • 批准号:
    3752418
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
  • 资助国家:
    美国
  • 起止时间:
  • 项目状态:
    未结题

项目摘要

This project seeks to develop targeted agents which disrupt cellular signal transduction, in addition to or instead of inhibition of protein synthesis. Work from LBC had previously shown that cholera toxin (CT) can inhibit the growth of certain carcinoma cell lines. Therefore efforts during the past year have focused on first, creating novel means of delivering CT-A chain to the surface of malignant cells, and second, defining novel targets in clinically relevant circumstances at which CT might be directed. We have constructed artificial genes in which the CT-A chain nucleotide sequence is fused in frame with a segment of diphtheria toxin (DT) sequence important for membrane translocation, and this segment is in turn also in frame with sequences encoding, in separate constructs, IL-2 and EGF. Such constructs could target neoplasms bearing receptors for these growth factors. We are now attempting to express these constructs in a way that will allow retention of enzymatic activity by CT. We have also defined in a series of leukemic specimens from patients with cutaneous T-cell lymphoma (CTCL) that IL-7 is an important co-stimulatory growth factor with IL-2, that IL-7 receptor and IL-7 ligand m-RNA are expressed in a fraction of patient-derived specimens, and that IL-7 stimulation leads to up regulation of both IL-7 and IL-2 receptors. We have completed a clinical trial which demonstrated clinical activity of DAB486 IL-2, a chimeric diphtheria toxin-IL2 fusion protein in CTCL. Collectively these studies point to the importance of the IL-7 and IL-2 receptor systems in CTCL as important targets for therapeutic agents which can disrupt intracellular signalling. We are also continuing ongoing studies of anti DC19 and anti CD22 antibodies as means of analogously disrupting signals in B-cells, and of anti-DC19 and anti-CD22 directed immunotoxins in patients with B-cell lymphoma.
该项目旨在开发破坏细胞的靶向药物

项目成果

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E SAUSVILLE其他文献

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{{ truncateString('E SAUSVILLE', 18)}}的其他基金

SECOND MESSENGER AND RECEPTOR SYSTEMS IN HUMAN SCLC
人类 SCLC 中的第二信使和受体系统
  • 批准号:
    3916617
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
IMMUNOTOXIN PROTOCOLS
免疫毒素方案
  • 批准号:
    5201307
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
SECOND MESSENGER AND RECEPTOR SYSTEMS IN HUMAN SCLC
人类 SCLC 中的第二信使和受体系统
  • 批准号:
    3939550
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
ENDOTHELIAL CELL TARGETED CANCER TREATMENT
内皮细胞靶向癌症治疗
  • 批准号:
    3838151
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
PRECLINICAL AND CLINICAL PHARMACOLOGY OF PROTEIN KINASE ANTAGONISTS
蛋白激酶拮抗剂的临床前和临床药理学
  • 批准号:
    3752419
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
G-PROTEIN EFFECTORS AS TARGETS FOR ANTINEOPLASTIC THERAPIES
G 蛋白效应物作为抗肿瘤治疗的靶点
  • 批准号:
    3774670
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
PROTEIN KINASE ANTAGONISTS--PRECLINICAL AND CLINICAL STUDIES
蛋白激酶拮抗剂——临床前和临床研究
  • 批准号:
    2464490
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
ENDOTHELIAL CELL TARGETED CANCER TREATMENT
内皮细胞靶向癌症治疗
  • 批准号:
    3774671
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
ENDOTHELIAL CELL TARGETED CANCER TREATMENT
内皮细胞靶向癌症治疗
  • 批准号:
    3752421
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
PRECLINICAL PHARMACOLOGY OF PROTEIN KINASE ANTAGONISTS
蛋白激酶拮抗剂的临床前药理学
  • 批准号:
    3853203
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:

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Analysis of expression of Cd antigens in retinoblastoma, and its application for disease classification and therapeutic strategy
视网膜母细胞瘤中Cd抗原的表达分析及其在疾病分类和治疗策略中的应用
  • 批准号:
    25670726
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
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