THE PERCOLATION OF MONOCLONAL ANTIBODIES INTO TUMORS
THE PERCOLATION OF MONOCLONAL ANTIBODIES INTO TUMORS
批准号:
3916319
负责人:
J N WEINSTEIN
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
athymic mouse autoradiography biological transport chemical binding computer simulation fluorescent dye /probe growth factor human tissue immunoglobulins laboratory mouse ligands lung neoplasms lymphokines mathematical model melanoma metastasis monoclonal antibody neoplasm /cancer chemotherapy neoplasm /cancer immunotherapy
中文摘要
在单克隆抗体(或其他生物配体)可以标记之前
英文摘要
Before a monoclonal antibody (or other biological ligand) can label
or kill a tumor cell, it must first reach that cell. For portions
of a tumor far from the nearest blood vessel or other source of
antibody, access may be limited by the rate at which the molecule
can "percolate" through the extracellular space. We are
investigating the spatial and temporal profiles of immunoglobulin
(Ig) distribution generated by diffusion and convection through
tumors, taking into account the possibilities of (a) saturable
specific binding to cells, (b) nonsaturable, nonspecific binding,
and (c) metabolic degradation.
We first developed theoretical models of the percolation process.
Significant predictions thus far include the following: (1) The
diffusion coefficient and/or hydraulic conductivity may limit flux
of antitumor Ig through tumors. (2) The flux of non-binding
control Ig is much less likely to be limited by diffusion or
convection. Nonspecific Ig's penetrate more deeply and more
quickly into the tumor. (3) Even with saturable binding (but not
metabolism), the "C times T" exposure of tumor cells to antibody
will be the same throughout the mass. (4) Metabolism will decrease
the relative "C times T" exposure of cells farther from the source.
This may be a major barrier to effective treatment of solid tumors
with ligand molecules. (5) Most interesting, antibodies with low
affinity may be preferable at a given dose to those with high
affinity for some therapeutic applications.
We plan to test predictions of the model using micrometastases of
human melanoma in nude mice. The distribution of antibody will be
determined by fluorescence techniques and autoradiography.
Concepts arising from this study are being applied to the design
of clinical studies with monoclonal antibodies.
In addition to the investigations of immunoglobulin and other
ligands as administered agents, we are considering the physiology
of endogenous molecular species including the lymphokines and
growth factors.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
THE PHARMACOLOGY OF MONOCLONAL ANTIBODIES AND OTHER BIOLOGICAL LIGANDS
-
批准号:3796466
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
STUDIES OF LIPID-PROTEIN AND PROTEIN-PROTEIN INTERACTIONS IN HIV
-
批准号:3939287
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
MONOCLONAL ANTIBODIES IN THE LYMPHATICES FOR DIAGNOSIS AND THERAPY OF TUMORS
-
批准号:3939288
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
COMBINATION THERAPY FOR CANCER AND AIDS
-
批准号:2468450
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
MICROPHARMACOLOGY OF BIOLOGICAL LIGANDS
-
批准号:3774703
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
COMBINATION THERAPY FOR CANCER AND AIDS
-
批准号:3752462
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
TARGETING LIPOSOMES FOR SELECTIVE INTERACTION WITH SPECIFIC CELLS AND TISSUES
-
批准号:3916314
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
COMBINATION THERAPY FOR CANCER AND AIDS
-
批准号:5201374
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
SELECTIVE CYTOTOXICITY IN THE LYMPHATICS
-
批准号:3813361
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
TARGETING LIPOSOMES FOR SELECTIVE INTERACTION WITH SPECIFIC CELLS AND TISSUES
-
批准号:3963006
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
COMBINATION THERAPY OF CANCER AND AIDS
-
批准号:3796474
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
COMBINATION CHEMOTHERAPY OF AIDS AND CANCER
-
批准号:3808532
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
COMBINATION CHEMOTHERAPY OF AIDS AND CANCER
-
批准号:3813375
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
TARGETING LIPOSOMES FOR SELECTIVE INTERACTION WITH SPECIFIC CELLS AND TISSUES
-
批准号:3939286
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
COMBINATION THERAPY FOR CANCER AND AIDS
-
批准号:6100915
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
MONOCLONAL ANTIBODIES IN THE LYMPHATICES FOR DIAGNOSIS AND THERAPY OF TUMORS
-
批准号:3963008
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
NEW STRATEGIES FOR DRUG DISCOVERY AND DEVELOPMENT
-
批准号:5201360
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
NEW STRATEGIES FOR DRUG DISCOVERY AND DEVELOPMENT
-
批准号:3752449
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
TARGETING LIPOSOMES FOR SELECTIVE INTERACTION WITH SPECIFIC CELLS AND TISSUES
-
批准号:3813355
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
STRUCTURE/FUNCTION RELATIONSHIPS IN TREATMENT OF CANCER AND AIDS
-
批准号:3813356
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:J N WEINSTEIN
-
依托单位:
海外基金