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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：
SUYU SHU
金额：
$ 34.43万
依托单位：
CLEVELAND CLINIC LERNER COM-CWRU
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：
https://reporter.nih.gov/project-details/6763097
关键词：
antigen presentation beta galactosidase biomedical equipment development cell fusion colony stimulating factor dendritic cells disease /disorder model electric field hybrid cells interleukin 4 ionophores laboratory mouse model design /development neoplasm /cancer immunotherapy neoplasm /cancer vaccine neoplastic cell nonhuman therapy evaluation vaccine 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.

（申请人摘要）肿瘤免疫治疗的疗效