Chaperone-rich cell lysate embedded with BCR-ABL peptide demonstrates enhanced anti-tumor activity against a murine BCR-ABL positive leukemia.
Chaperone-rich cell lysate embedded with BCR-ABL peptide demonstrates enhanced anti-tumor activity against a murine BCR-ABL positive leukemia.
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嵌入 BCR-ABL 肽的富含分子伴侣的细胞裂解物表现出增强的针对小鼠 BCR-ABL 阳性白血病的抗肿瘤活性。
DOI：
10.1096/fj.06-7843com
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Katsanis,Emmanuel
中科院分区：
文献类型：
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作者：
Kislin,KerriL;Marron,MarilynT;Li,Gang;Graner,MichaelW;Katsanis,Emmanuel
从肿瘤来源纯化后，伴侣蛋白是有效的抗肿瘤疫苗，其中一些正在进行临床试验。此类疫苗最终会产生肿瘤特异性 T 细胞反应，暗示适应性免疫的作用。我们开发了一种快速有效的程序，利用等电聚焦技术从肿瘤或正常组织中获取疫苗，称为富含分子伴侣的细胞裂解物（CRCL）。肿瘤相关肽是 T 细胞介导的抗癌免疫的货币，据信是由伴侣疫苗提供的。我们的目的是证明我们有能力操纵 CRCL 疫苗的肽抗原库作为一种新型抗癌策略。我们的方法使我们能够利用CRCL的免疫刺激活性和承载能力来制备“设计”CRCL，以定量获取和递送外源抗原肽（例如，源自慢性粒细胞白血病中的致癌BCR/ABL蛋白）。使用基于荧光和抗原呈递测定，我们确定大量的外源添加肽可以在“设计的”CRCL 中积累，并可以刺激 T 细胞激活。此外，我们得出的结论是，不含其他抗原的肽嵌入 CRCL 可以产生针对预先建立的小鼠白血病的强大免疫力。设计者 CRCL 允许通过将抗原嵌入来自正常组织的 CRCL 来开发针对表达已知抗原的癌症的个性化疫苗。–Kislin, K. L.、Marron, M. T.、Li, G. Graner M. W. Katsanis E. 嵌入 BCR-ABL 肽的富含伴侣的细胞裂解物显示出针对小鼠 BCR-ABL 阳性白血病的增强的抗肿瘤活性FASEB J.21， 2173–2184 (2007)
Chaperone proteins are effective antitumor vaccines when purified from a tumor source, some of which are in clinical trials. Such vaccines culminate in tumor‐specific T cell responses, implicating the role of adaptive immunity. We have developed a rapid and efficient procedure utilizing an isoelectric focusing technique to obtain vaccines from tumor or normal tissues called chaperone‐rich cell lysate (CRCL). Tumor‐associated peptides the currency of T cell‐mediated anticancer immunity are believed to be purveyed by chaperone vaccines. Our purpose was to demonstrate our ability to manipulate the peptide antigen repertoire of CRCL vaccines as a novel anticancer strategy. Our methods allow us to prepare “designer” CRCL utilizing the immunostimulation activity and the carrying capacity of CRCL to quantitatively acquire and deliver exogenous antigenic peptides(e.g.,derived from the oncogenic BCR/ABL protein in chronic myelogenous leukemia). Using fluorescence‐based and antigen‐presentation assays we determined that significant quantities of exogenously added peptide could accumulate in “designer” CRCL and could stimulate T cell activation. Further, we concluded that peptide‐embedded CRCL devoid of other antigens could generate potent immunity against pre‐established mu‐rine leukemia. Designer CRCL allows for the development of personalized vaccines against cancers expressing known antigens by embedding antigens into CRCL derived from normal tissue.–Kislin, K. L., Marron, M. T., Li, G. Graner M. W. Katsanis E. Chaperone‐rich cell lysate embedded with BCR‐ABL peptide demonstrates enhanced anti‐tumor activity against a murine BCR‐ABL positive leukemiaFASEB J.21, 2173–2184 (2007)