GENERATION AND CLINICAL USE OF HUMAN ANTIID ANTIBODIES
GENERATION AND CLINICAL USE OF HUMAN ANTIID ANTIBODIES
批准号:
2100172
负责人:
MANSOOR N SALEH
金额:
$16.92万
依托单位国家:
美国
项目类别:
财政年份:
1994
资助国家:
美国
项目状态:
已结题
起止时间:
1994-07-25 至 1997-06-30
关键词:
B lymphocyte T lymphocyte antiidiotype antibody clinical trials disease /disorder model drug adverse effect enzyme linked immunosorbent assay human subject human therapy evaluation humoral immunity immunomodulators laboratory rabbit melanoma monoclonal antibody neoplasm /cancer chemotherapy neoplasm /cancer immunotherapy neoplasm /cancer vaccine tumor antigens western blottings
中文摘要
肿瘤相关抗原(TAA)通常是非特异性的或仅是非常弱的。
免疫原性,因此不促进肿瘤排斥。整体
该研究的目的是产生人抗独特型
(抗Id)单克隆抗体(MoAb)模拟黑色素瘤相关
GD 2抗原,最终目的是临床应用这些
作为抗肿瘤疫苗的试剂。
暴露于抗肿瘤单克隆抗体的患者通常会产生免疫应答,
外来蛋白质。这种人体免疫反应的一个组成部分是抗Id;
可显示与MoAb的抗原结合位点结合;并且可
潜在地模拟靶TAA(“内部图像”抗Id)。
该项目的重点将是:
a.为了从接受抗GD 2单克隆抗体治疗的患者中收获淋巴细胞,
建立并使用它们来产生模拟GD 2的人抗Ids
抗原的
B.为了表征这些试剂产生的免疫应答,
关于B细胞和T细胞抗-抗-Id和抗-GD 2的动物模型
免疫反应。这些研究将确定那些真正
模拟GD 2抗原,可用作免疫模拟替代品。
C.一方面表征抗Id上模拟TAA的位点,
产生抗肿瘤免疫反应。为此,V区基因
将进行测序
D.在相关动物模型中确定剂量和免疫佐剂
组合,将引发最有效的免疫和抗肿瘤
反应
e.在高风险/低肿瘤负荷中进行I期临床试验
黑色素瘤患者研究其毒性和免疫反应
抗Id疫苗
这些研究将提供深入了解参与免疫机制,
人抗Id疫苗的应用,并产生新的选择,
黑色素瘤以及其他人类恶性肿瘤的生物治疗。
英文摘要
Tumor associated antigens (TAA) are generally non- or only very weakly
immunogenic and therefore do not promote tumor rejection. The overall
objective of the proposed research is to generate human anti-idiotypic
(anti-Id) monoclonal antibodies (MoAb)that mimic the melanoma associated
GD2 antigen, with the ultimate purpose of clinically applying these
reagents as anti-tumor vaccines.
Patients exposed to anti-tumor MoAbs generally mount an immune response to
the foreign protein. A component of this human immune response is anti-Id;
can be shown to bind to the antigen combining site of the MoAb; and can
potentially mimic the target TAA ("internal image" anti-Id).
The focus of the project will be:
a. To harvest lymphocytes from patients treated with anti-GD2 MoAbs at our
institution and use these to generate human anti-Ids that mimic the GD2
antigen.
b. To characterize the immune response generated by these reagents in
animal models in regards to B-cell and T-cell anti-anti-Id and anti-GD2
immune responses. These studies will identify those anti-Ids that truly
mimic the GD2 antigen and can be used as immunomimetic surrogates.
c. To characterize sites on the anti-Id that mimic the TAA on one hand and
generate the anti-tumor immune response. To this end, the V-region genes
of the anti-Id will be sequenced.
d. To identify, in relevant animal models, the dose and immune adjuvant
combination that will elicit the most effective immune and anti-tumor
response.
e. To conduct a phase I clinical trial in high risk/low tumor burden
melanoma patients to study the toxicity and immunologic response of the
anti-Id vaccine.
These studies will provide insight into the immune mechanisms involved in
the application of human anti-Id vaccines and generate novel options for
the biologic therapy of melanoma as well as other human malignancies.
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会议论文
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