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甲磺酸伊马替尼能有效地与富含伴侣蛋白的负载细胞裂解物的树突状细胞结合,用于治疗bcr-abl+小鼠白血病。

Imatinib mesylate effectively combines with chaperone-rich cell lysate-loaded dendritic cells to treat bcr-abl+ murine leukemia.

作者信息

Zeng Yi, Graner Michael W, Feng Hanping, Li Gang, Katsanis Emmanuel

机构信息

Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona, Tucson, AZ 85724, USA.

出版信息

Int J Cancer. 2004 Jun 10;110(2):251-9. doi: 10.1002/ijc.20115.

Abstract

Imatinib mesylate has become an effective agent for the treatment of chronic myeloid leukemia (CML). However, the development of drug resistance has led to examination of combination therapies. In this study, we investigated the effects of combining imatinib with immunotherapy against a murine bcr-abl(+) leukemia, 12B1. We have previously shown that multiple chaperone proteins may be enriched into a vaccine form from tumor cell lysates by a free-solution isoelectric focusing method. We refer to these vaccines as chaperone-rich cell lysates (CRCLs) and have found that they are potent immunologic agents against a variety of murine tumors, including 12B1. We now demonstrate that the combination of imatinib with dendritic cells loaded with 12B1-derived CRCL yields high activation of anti-12B1-specific T cells and potent antitumor activity, resulting in tumor-free survival in up to 63% of mice with bcr-abl(+) 12B1 tumors. Our data suggest that immunotherapy can be effectively combined with imatinib for the treatment of CML.

摘要

甲磺酸伊马替尼已成为治疗慢性粒细胞白血病(CML)的有效药物。然而,耐药性的出现促使人们对联合疗法进行研究。在本研究中,我们研究了伊马替尼与针对小鼠bcr-abl(+)白血病12B1的免疫疗法联合使用的效果。我们之前已经表明,通过自由溶液等电聚焦方法,多种伴侣蛋白可从肿瘤细胞裂解物中富集到疫苗形式。我们将这些疫苗称为富含伴侣蛋白的细胞裂解物(CRCLs),并发现它们是针对包括12B1在内的多种小鼠肿瘤的有效免疫剂。我们现在证明,伊马替尼与负载有12B1衍生的CRCL的树突状细胞联合使用,可高度激活抗12B1特异性T细胞并产生强大的抗肿瘤活性,使高达63%的患有bcr-abl(+) 12B1肿瘤的小鼠实现无瘤存活。我们的数据表明,免疫疗法可与伊马替尼有效联合用于治疗CML。

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