IMMUNOTHERAPY WITH ELECTROFUSED DENDRITIC TUMOR HYBRIDS
电融合树突状肿瘤杂交体的免疫治疗
基本信息
- 批准号:6763097
- 负责人:
- 金额:$ 34.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-07-01 至 2006-06-30
- 项目状态:已结题
- 来源:
- 关键词:antigen presentationbeta galactosidasebiomedical equipment developmentcell fusioncolony stimulating factordendritic cellsdisease /disorder modelelectric fieldhybrid cellsinterleukin 4ionophoreslaboratory mousemodel design /developmentneoplasm /cancer immunotherapyneoplasm /cancer vaccineneoplastic cellnonhuman therapy evaluationvaccine development
项目摘要
DESCRIPTION: (Applicant's Abstract) The efficacy of cancer immunotherapy
depends highly on the potency and duration of the induced immune response. To
date, cancer vaccinations have utilized intact tumor cells, naive proteins,
CTL-defined peptides, nucleic acids, cell membranes and recombinant viruses as
well as genetically modified tumors. Although some approaches have been to
increase the antigen presenting capacity of tumor cells, in most cases, the
dominant role of host antigen-presenting cells (APCs) has been demonstrated.
Among various APCs, dendritic cells (DCs) seem to have the essential properties
required for eliciting T-cell responses: migration and homing, antigen
processing and presentation and co-stimulation. Recently, DCs have been used to
present tumor antigens. This is generally achieved by pulsing DCs with
peptides, tumor lysates or RNA derived from neoplastic cells. It has also been
demonstrated that immunization with DC-tumor fused chimeric cells results in
the regression of established metastases. Fused cells should have the ability
to elicit both MHC class I and II-restricted responses by processing and
presenting known and undefined tumor antigens. In most reported cases, however,
fusion has been accomplished with the use of PEG, resulting in low efficiency
and high toxicity. With this approach, it may be the technical rather than
conceptual aspects that limit its application. The applicant has recently
demonstrated that fusion of DCs and tumor cells by applying electric field
pulses is at least 10-fold more efficient than that by PEG. Interestingly,
electrofusion of immature DCs with tumor cells resulted in hybrid cells having
characteristics of mature DCs with high expression of MHC class II, B7.1 and
B7.2 molecules. To analyze biological and immunological functions of these
artificially generated chimeric cells, the current application will utilize the
well-characterized model tumor-associated antigen, B-galactosidase, to address
fundamental issues. Subsequent experiments will use several weakly and poorly
immunogenic tumors. The goal of the current application is to develop in murine
models, the principles and methodologies for utilizing DCs fused with entire
tumor cells for active and adoptive immunotherapy of cancer. The specific aims
are: 1) To optimize electrofusion techniques; 2) To characterize antigen
processing and presentation, MHC restriction and trafficking patterns of fused
cells; 3) To analyze characteristics of immune responses elicited by DC-tumor
fused cells; 4) To explore the therapeutic potential of the chimeric cells; and
5) To develop methods for primary in vitro immunization for generating
tumor-specific T cells.
描述:(申请人的摘要)癌症免疫疗法的功效
这在很大程度上取决于诱导的免疫应答的效力和持续时间。到
迄今为止,癌症疫苗已经利用了完整的肿瘤细胞,天然蛋白,
CTL定义的肽、核酸、细胞膜和重组病毒,
以及转基因肿瘤。虽然有些方法已经被用于
增加肿瘤细胞的抗原呈递能力,在大多数情况下,
已经证明了宿主抗原呈递细胞(APC)的主导作用。
在各种APC中,树突状细胞(Dendritic cells,DC)似乎具有基本的特性,
引发T细胞反应所需的:迁移和归巢,抗原
加工、呈现和共刺激。最近,DC已被用于
呈现肿瘤抗原。这通常是通过脉冲DC来实现的,
肽、肿瘤裂解物或源自肿瘤细胞的RNA。还已经
证明用DC-肿瘤融合嵌合细胞免疫导致
已经确定的转移的消退。融合细胞应该有能力
通过加工和诱导MHC I类和II类限制性反应,
呈现已知和未定义的肿瘤抗原。然而,在大多数报告的案件中,
融合已经用PEG完成,导致效率低
且毒性高。通过这种方法,它可能是技术性的,而不是
限制其应用的概念方面。申请人最近
证明了通过施加电场使DC和肿瘤细胞融合,
脉冲的效率至少是PEG的10倍。有趣的是,
未成熟DC与肿瘤细胞的电融合产生具有以下特征的杂交细胞:
具有高表达MHC II类、B7.1和
B7.2分子。分析其生物学和免疫学功能
人工产生的嵌合细胞,本申请将利用
良好表征的模型肿瘤相关抗原,B-半乳糖苷酶,以解决
根本问题。后续的实验将使用几个弱和差
免疫原性肿瘤本申请的目标是在鼠中开发
利用发展中国家的原则和方法
肿瘤细胞用于癌症的主动和过继免疫治疗。具体目标
目的:1)优化电融合技术; 2)表征抗原
融合蛋白的加工和呈递、MHC限制和运输模式
分析DC-肿瘤诱导的免疫应答特点
4)探索嵌合细胞的治疗潜力;以及
5)建立一级体外免疫方法,
肿瘤特异性T细胞。
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Electrofusion of syngeneic dendritic cells and tumor generates potent therapeutic vaccine.
- DOI:10.1016/j.cellimm.2003.09.005
- 发表时间:2003-10
- 期刊:
- 影响因子:4.3
- 作者:J. Kjaergaard;K. Shimizu;S. Shu
- 通讯作者:J. Kjaergaard;K. Shimizu;S. Shu
Therapeutic immune response induced by electrofusion of dendritic and tumor cells.
- DOI:10.1016/s0008-8749(03)00009-1
- 发表时间:2002-11
- 期刊:
- 影响因子:4.3
- 作者:Hiroshi Tanaka;K. Shimizu;Takashi Hayashi;S. Shu
- 通讯作者:Hiroshi Tanaka;K. Shimizu;Takashi Hayashi;S. Shu
Therapeutic vaccine generated by electrofusion of dendritic cells and tumour cells.
通过树突状细胞和肿瘤细胞的电融合产生的治疗性疫苗。
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:Kuriyama,H;Shimizu,K;Lee,W;Kjaergaard,J;Parkhurst,MR;Cohen,PA;Shu,S
- 通讯作者:Shu,S
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{{ truncateString('SUYU SHU', 18)}}的其他基金
Immunotherapy with Dendritic-Allogeneic Tumor Cells
树突状同种异体肿瘤细胞的免疫治疗
- 批准号:
7125606 - 财政年份:2004
- 资助金额:
$ 34.43万 - 项目类别:
Immunotherapy with Dendritic-Allogeneic Tumor Cells
树突状同种异体肿瘤细胞的免疫治疗
- 批准号:
6928007 - 财政年份:2004
- 资助金额:
$ 34.43万 - 项目类别:
Immunotherapy with Dendritic-Allogeneic Tumor Cells
树突状同种异体肿瘤细胞的免疫治疗
- 批准号:
7252652 - 财政年份:2004
- 资助金额:
$ 34.43万 - 项目类别:
Immunotherapy with Dendritic-Allogeneic Tumor Cells
树突状同种异体肿瘤细胞的免疫治疗
- 批准号:
6700500 - 财政年份:2004
- 资助金额:
$ 34.43万 - 项目类别:
Immunotherapy with Dendritic-Allogeneic Tumor Cells
树突状同种异体肿瘤细胞的免疫治疗
- 批准号:
7432446 - 财政年份:2004
- 资助金额:
$ 34.43万 - 项目类别:
Immunotherapy with Dendritic-Allogeneic Tumor Cells
树突状同种异体肿瘤细胞的免疫治疗
- 批准号:
7714833 - 财政年份:2004
- 资助金额:
$ 34.43万 - 项目类别:
IMMUNOTHERAPY WITH ELECTROFUSED DENDRITIC TUMOR HYBRIDS
电融合树突状肿瘤杂交体的免疫治疗
- 批准号:
6205329 - 财政年份:2000
- 资助金额:
$ 34.43万 - 项目类别:
IMMUNOTHERAPY WITH ELECTROFUSED DENDRITIC TUMOR HYBRIDS
电融合树突状肿瘤杂交体的免疫治疗
- 批准号:
6377653 - 财政年份:2000
- 资助金额:
$ 34.43万 - 项目类别:
IMMUNOTHERAPY WITH ELECTROFUSED DENDRITIC TUMOR HYBRIDS
电融合树突状肿瘤杂交体的免疫治疗
- 批准号:
6514261 - 财政年份:2000
- 资助金额:
$ 34.43万 - 项目类别:
IMMUNOTHERAPY WITH ELECTROFUSED DENDRITIC TUMOR HYBRIDS
电融合树突状肿瘤杂交体的免疫治疗
- 批准号:
6658985 - 财政年份:2000
- 资助金额:
$ 34.43万 - 项目类别:
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