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CANCER IMMUNOTHERAPY USING AUTOLOGOUS TUMOR CELLS COMBINED WITH ALLOGENEIC CYTOKINE-SECRETING CELLS

机译:结合自身标志性肿瘤细胞和同种细胞因子分泌细胞的肿瘤免疫治疗

摘要

This invention comprises cellular vaccines and methods of using them in cancerimmunotherapy, particularly in humans. The vaccines comprise a source of tumor-associated antigen, and a cytokine-secreting cell line. Tumor antigen may beprovided in the form of primary tumor cells, tumor cell lines or tumorextracts prepared from the subject. In certain embodiments of the invention,the cytokine-secreting line is a separate tumor line that is allogeneic to thepatient and genetically altered so as to produce a cytokine at an elevatedlevel. Exemplary cytokines are IL-4, GM-CSF, IL-2, TNF-.alpha., and M-CSF inthe secreted or membrane-bound form. In these embodiments, the cytokine-producing cells provide immunostimulation in trans to generate a specificimmune response against the tumor antigen. Vaccines may be tailored for eachtype of cancer or for each subject by mixing tumor antigen with a favorablenumber of cytokine-producing cells, or with a cocktail of such cells producinga plurality of cytokines at a favorable ratio.
机译:本发明包括细胞疫苗及其在癌症中的使用方法免疫疗法,尤其是在人类中。疫苗包含肿瘤来源相关抗原,以及分泌细胞因子的细胞系。肿瘤抗原可能是以原发性肿瘤细胞,肿瘤细胞系或肿瘤的形式提供从受试者制备的提取物。在本发明的某些实施例中,细胞因子分泌系是与肿瘤同种异体的单独肿瘤系患者并经过基因改造,从而在升高的水平上产生细胞因子水平。示例性细胞因子是IL-4,GM-CSF,IL-2,TNF-α和M-CSF。分泌形式或膜结合形式。在这些实施方案中,细胞因子产生细胞提供反式免疫刺激以产生特异性对肿瘤抗原的免疫应答。疫苗可以针对每种情况量身定制癌症类型或针对每个受试者,将肿瘤抗原与有利数量的细胞因子产生细胞,或与此类细胞产生的混合物多种细胞因子以有利的比例存在。

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