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DNA-based Vaccine for Treatment of Oral Carcinoma

用于治疗口腔癌的 DNA 疫苗

基本信息

批准号：
7065166
负责人：
EDWARD P. COHEN
金额：
$ 26.64万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-15 至 2007-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7065166
关键词：
DNA antigen presenting cell cytotoxic T lymphocyte dendritic cells disease /disorder model enzyme linked immunosorbent assay fibroblasts head /neck neoplasm laboratory mouse mouth neoplasms neoplasm /cancer immunotherapy nonhuman therapy evaluation oral health squamous cell carcinoma transfection tumor antigens vector vaccine

项目摘要

DESCRIPTION: Vaccine development for oral carcinoma is the current major research objective of my laboratory. The long-term objective is to develop a vaccine that can be used in the overall management of patients with squamous cell carcinoma of the head and neck (SCCHN). The vaccination strategy combines known requirements for generation of a robust anti tumor immune response--antigen presentation, allogeneic stimulation and the secretion of immune-augmenting cytokines. The vaccine is prepared by transfer of DNA from squamous carcinoma cells into a highly immunogenic syngeneic/allogeneic cell line in which genes specifying tumor associated antigens (TAAs) are expressed. The recipient cells are modified in advance of DNA-transfer to secrete cytokines. This type of vaccine is based on the principle that TAAs are the products of mutant and dysregulated genes in cancer cells and that transfer of tumor-DNA into recipient cells results in stable integration and long-term expression of the genes specifying TAAs. Prior published data in mice indicate that immunization with transfected cells induced strong anti tumor immune responses, immunological memory and prolongation of survival. Our recent studies (PNAS, 99: 9415-9420, 2002) confirm the immunogenic properties of recipient cells transfected with DNA from human oral carcinomas. This type of vaccine has a number of advantages, including the selection of immunogenic recipient cells, in which the transferred DNA is replicated. Thus, the vaccine can be prepared with DNA derived from small amounts of tumor tissue. Further studies in a mouse model of oral carcinoma are now required to define the mechanisms of the immunotherapeutic effects of the vaccine and to optimize this promising strategy. Using murine antigen presenting cells transfected with DNA from squamous carcinomas, the minimum amount of tumor tissue required to prepare an effective vaccine and the cell types mediating tumor rejection will be determined. The transfected cell-population will be enriched for cells that express TAAs, to increase the therapeutic potential of the vaccine. Its possible toxic effects will be evaluated. These studies will provide insights into the mechanism of tumor rejection and guidelines for optimization of the vaccination strategy. It is expected that development of an effective vaccine to be used alone or in combination with conventional therapy will expand the future therapeutic options available for patients with oral cancer.

描述：口腔癌疫苗的开发是我实验室目前的主要研究目标。长期目标是开发一种疫苗，可用于头颈部鳞状细胞癌（SCCHN）患者的全面管理。疫苗接种策略结合了产生强大的抗肿瘤免疫应答的已知要求-抗原呈递，同种异体刺激和免疫增强细胞因子的分泌。该疫苗通过将来自鳞状细胞癌细胞的DNA转移到高度免疫原性的同基因/同种异体细胞系中来制备，其中表达指定肿瘤相关抗原（TAA）的基因。受体细胞在DNA转移之前被修饰以分泌细胞因子。这种类型的疫苗基于以下原理：TAA是癌细胞中突变和失调基因的产物，并且肿瘤DNA转移到受体细胞中导致指定TAA的基因的稳定整合和长期表达。先前发表的小鼠数据表明，用转染的细胞免疫诱导强烈的抗肿瘤免疫应答、免疫记忆和存活延长。我们最近的研究（PNAS，99：9415-9420，2002）证实了用来自人口腔癌的DNA转染的受体细胞的免疫原性。这种类型的疫苗具有许多优点，包括选择免疫原性受体细胞，其中转移的DNA被复制。因此，疫苗可以用来自少量肿瘤组织的DNA制备。现在需要在小鼠口腔癌模型中进行进一步的研究，以确定疫苗免疫效应的机制，并优化这种有前途的策略。使用用来自鳞状细胞癌的DNA转染的鼠抗原呈递细胞，将确定制备有效疫苗所需的最小量的肿瘤组织和介导肿瘤排斥的细胞类型。转染的细胞群将富集表达TAA的细胞，以增加疫苗的治疗潜力。将评估其可能的毒性作用。这些研究将为肿瘤排斥机制和疫苗接种策略的优化提供指导。预计开发一种单独使用或与常规治疗联合使用的有效疫苗将扩大口腔癌患者未来的治疗选择。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Immunity to breast cancer in mice immunized with fibroblasts transfected with a cDNA expression library derived from small numbers of breast cancer cells.

用源自少量乳腺癌细胞的 cDNA 表达文库转染的成纤维细胞进行免疫接种的小鼠对乳腺癌的免疫力。

DOI：
10.1038/sj.cgt.7700853
发表时间：
2005
期刊：
Cancer gene therapy.
影响因子：
0
作者：
SungKim,Tae;Cohen,EdwardP
通讯作者：
Cohen,EdwardP

Immunity to Trop-1, a newly identified breast cancer antigen, inhibits the growth of breast cancer in mice.

DOI：
10.1016/j.vaccine.2010.09.057
发表时间：
2010-11
期刊：
Vaccine
影响因子：
5.5
作者：
Byeong C Lee;M. Jung;D. Cho;I. O-Sullivan;E. Cohen;T. S. Kim
通讯作者：
Byeong C Lee;M. Jung;D. Cho;I. O-Sullivan;E. Cohen;T. S. Kim

Immunity to squamous carcinoma in mice immunized with dendritic cells transfected with genomic DNA from squamous carcinoma cells.

用转染鳞状癌细胞基因组 DNA 的树突状细胞免疫小鼠，对鳞状癌具有免疫力。

DOI：
10.1038/sj.cgt.7700847
发表时间：
2005
期刊：
Cancer gene therapy
影响因子：
6.4
作者：
O-Sullivan,InSug;Ng,LaurenK;Martinez,DonM;Kim,TaeS;Chopra,Amla;Cohen,EdwardP
通讯作者：
Cohen,EdwardP

New strategy for the identification of squamous carcinoma antigens that induce therapeutic immune responses in tumor-bearing mice.

鉴定在荷瘤小鼠中诱导治疗性免疫反应的鳞状癌抗原的新策略。