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
- 来源:
- 关键词:antitumor antibody clone cells folate galactose galactosyltransferases gene targeting genetically modified animals humoral immunity immunoconjugates laboratory mouse neoplasm /cancer immunology neoplasm /cancer immunotherapy nonhuman therapy evaluation ovary neoplasms receptor binding vitamin receptor
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)
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{{ truncateString('MOO J CHO', 18)}}的其他基金
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:
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