Graner Michael W, Zeng Yi, Feng Hanping, Katsanis Emmanuel
Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona, 1501 North Campbell Ave., P.O. Box 245073, Tucson, AZ 85724, USA.
Cancer Immunol Immunother. 2003 Apr;52(4):226-34. doi: 10.1007/s00262-002-0359-2. Epub 2003 Feb 18.
With the clinical use of purified, tumor-derived chaperone proteins as anti-cancer vaccines already in clinical trial stages, we have focused our attention on the utility of chaperone-rich cell lysates (CRCL) in cancer immunotherapy. CRCL, as prepared from tumor lysates via a free solution-isoelectric focusing (FS-IEF) technique, is a high-yield vaccine enriched for numerous chaperone proteins. We have compared the efficacy of CRCL vaccines to that of individual chaperone protein vaccines in in vivo settings, including ELISPOT assays, tumor-growth assays and survival assays. In all experiments, CRCL vaccines were at least as effective, and in some settings perhaps even more effective, than either of the two most heavily studied components of CRCL, HSP70 and GRP94/gp96, in reduction in tumor growth and prolongation of survival in both prophylactic and pre-existing tumor settings against tumors of diverse origin and genetic background. Combining CRCL preparations with dendritic cells ex vivo resulted in a cellular vaccine that could eradicate pre-existing tumors in a high percentage of cases. The high yields of CRCL vaccines from small quantities of starting materials, the relative ease of its procurement and the functional data presented here suggest that CRCL vaccines are worthy of evaluation in pilot clinical trial cancer immunotherapy protocols.
随着纯化的肿瘤衍生伴侣蛋白作为抗癌疫苗已进入临床试验阶段，我们将注意力集中在了富含伴侣蛋白的细胞裂解物（CRCL）在癌症免疫治疗中的效用上。通过自由溶液等电聚焦（FS-IEF）技术从肿瘤裂解物中制备的CRCL是一种富含多种伴侣蛋白的高产疫苗。我们在体内实验中比较了CRCL疫苗与单个伴侣蛋白疫苗的功效，包括酶联免疫斑点分析、肿瘤生长分析和生存分析。在所有实验中，在预防和已有肿瘤的情况下，针对不同起源和遗传背景的肿瘤，CRCL疫苗在减少肿瘤生长和延长生存期方面至少与CRCL中研究最多的两个成分HSP70和GRP94/gp96一样有效，在某些情况下甚至可能更有效。将CRCL制剂与树突状细胞在体外结合可产生一种细胞疫苗，该疫苗能在高比例的病例中根除已有肿瘤。CRCL疫苗从少量起始材料中获得的高产率、相对容易的获取方式以及本文提供的功能数据表明，CRCL疫苗值得在癌症免疫治疗的试点临床试验方案中进行评估。
