TARGETING ENDOGENOUS ANTIBODIES TO OVARIAN CARCINOMA

针对卵巢癌的内源性抗体

基本信息

  • 批准号:
    6623365
  • 负责人:
  • 金额:
    $ 14.78万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2002
  • 资助国家:
    美国
  • 起止时间:
    2002-04-01 至 2004-09-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Humans and Old World primates naturally produce a significant amount of antibodies which recognize a particular galactosyl epitope, GAL alpha 1-3GAL. We have been interested in testing if these anti-Gal antibodies can be targeted to undesirable cancerous cells. Specifically we wish to explore a possibility of redirecting these endogenous antibodies to ovarian carcinoma cells which overexpress folate receptor isotype alpha (FR-alpha) by means of chemical conjugates of folic acid to the galactosyl epitope. The end result should be the cytolysis of the target cell. Towards this goal, the present application is concerned with the total synthesis of the folate-digalactose conjugates and development of an ovarian cancer model in immune competent mice. Preparation of the conjugate which can mediate anti-Gal binding to FR+ cells with high avidity is the main chemistry goal of the project. Our strategy is to introduce multiple copies, 2 and 4 copies, of the epitopes to one molecule of folic acid at an optimal distance between them. Chemical synthesis will be carried out on a solid-phase support. The conjugates will be tested with FR+/Gal- human nasopharyngeal carcinoma KB cells for their ability of promoting the anti-Gal binding to FR on the cell surface. Specificity of the interaction will be tested in the presence of free folic acid or free disaccharide as well as with a conjugate that contains lactose instead of GAL alpha 1-3GAL. The antibody binding will be conveniently characterized by means of FACS procedure. The biological goal of this project is to develop a mouse model of ovarian cancer that is suitable for testing anti-tumor activity of our folate conjugates in vivo. Since normal mice express the galactosyl epitopes in their tissue, we will have to use alpha 1,3-GALactosyltransferase-knockout (GT/KO) mice. It is known that GT/KO mice produce anti-Gal as in humans. We plan to transform the ovarian epithelial cells harvested from these mice in culture to tumor-forming cell lines following a procedure we have recently developed. They will be then transfected with murine cDNA encoding full length FR-alpha. Finally these GAL-/FR+cells will be introduced into peritoneum of healthy GT/KO mice. Our current approach to immunotherapy of ovarian cancer is unique in that we are using naturally occurring endogenous antibodies. Immune modulators in this application are all small molecules with MW < 3 kDa, rendering pharmacokinetic properties most favorable for sustained activity in peritoneal cavity as well as reduced potential side effects.
描述(由申请人提供):

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

MOO J CHO其他文献

MOO J CHO的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('MOO J CHO', 18)}}的其他基金

Systemic Delivery of CpG Oligonucleotides
CpG 寡核苷酸的全身递送
  • 批准号:
    8074537
  • 财政年份:
    2008
  • 资助金额:
    $ 14.78万
  • 项目类别:
Systemic Delivery of CpG Oligonucleotides
CpG 寡核苷酸的全身递送
  • 批准号:
    8260573
  • 财政年份:
    2008
  • 资助金额:
    $ 14.78万
  • 项目类别:
Systemic Delivery of CpG Oligonucleotides
CpG 寡核苷酸的全身递送
  • 批准号:
    7659407
  • 财政年份:
    2008
  • 资助金额:
    $ 14.78万
  • 项目类别:
Systemic Delivery of CpG Oligonucleotides
CpG 寡核苷酸的全身递送
  • 批准号:
    7524167
  • 财政年份:
    2008
  • 资助金额:
    $ 14.78万
  • 项目类别:
Systemic Delivery of CpG Oligonucleotides
CpG 寡核苷酸的全身递送
  • 批准号:
    7845014
  • 财政年份:
    2008
  • 资助金额:
    $ 14.78万
  • 项目类别:
pH- SENSITIVE BIS-DETERGENTS FOR MACROMOLECULAR DELIVERY
用于大分子输送的 pH 敏感双去污剂
  • 批准号:
    6776804
  • 财政年份:
    2004
  • 资助金额:
    $ 14.78万
  • 项目类别:
pH- SENSITIVE BIS-DETERGENTS FOR MACROMOLECULAR DELIVERY
用于大分子输送的 pH 敏感双去污剂
  • 批准号:
    6872986
  • 财政年份:
    2004
  • 资助金额:
    $ 14.78万
  • 项目类别:
TARGETING ENDOGENOUS ANTIBODIES TO OVARIAN CARCINOMA
针对卵巢癌的内源性抗体
  • 批准号:
    6465181
  • 财政年份:
    2002
  • 资助金额:
    $ 14.78万
  • 项目类别:
ASSAY SYSTEM FOR EVALUATING CELLULAR ANTISENSE DELIVERY
用于评估细胞反义递送的测定系统
  • 批准号:
    2900929
  • 财政年份:
    1998
  • 资助金额:
    $ 14.78万
  • 项目类别:
ASSAY SYSTEM FOR EVALUATING CELLULAR ANTISENSE DELIVERY
用于评估细胞反义递送的测定系统
  • 批准号:
    2602743
  • 财政年份:
    1998
  • 资助金额:
    $ 14.78万
  • 项目类别:

相似海外基金

Establishment and functional analysis of mouse cultured skeletal muscle clone cells lacking insulin 1 and 2
胰岛素1、2缺失小鼠骨骼肌克隆细胞的建立及功能分析
  • 批准号:
    21K19725
  • 财政年份:
    2021
  • 资助金额:
    $ 14.78万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
Establishment of the iPS cells derived from the paroxysmal nocturnal hemoglobinuria clone cells and its application to a study of bone marrow failure.
源自阵发性睡眠性血红蛋白尿克隆细胞的 iPS 细胞的建立及其在骨髓衰竭研究中的应用。
  • 批准号:
    25860785
  • 财政年份:
    2013
  • 资助金额:
    $ 14.78万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了