Tumor-derived chaperone-rich cell lysates are effective therapeutic vaccines against a variety of cancers
Tumor-derived chaperone-rich cell lysates are effective therapeutic vaccines against a variety of cancers
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DOI：
10.1007/s00262-002-0359-2
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发表时间：
2003-04-01
影响因子：
5.8
通讯作者：
Katsanis, E
中科院分区：
文献类型：
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作者：
Graner, MW;Yi, Z;Katsanis, E
随着纯化的肿瘤源性伴侣蛋白作为抗癌疫苗的临床应用已经处于临床试验阶段，我们已经将注意力集中在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。通过游离溶液-等电聚焦（FS-IEF）技术从肿瘤裂解物制备的CRCL是富含多种伴侣蛋白的高产疫苗。我们已经比较了CRCL疫苗与个体伴侣蛋白疫苗在体内环境中的功效，包括ELISPOT测定、肿瘤生长测定和存活测定。在所有实验中，CRCL疫苗在针对不同来源和遗传背景的肿瘤的预防性和预先存在的肿瘤环境中，在减少肿瘤生长和延长存活方面至少与CRCL的两种最深入研究的组分HSP 70和GRP 94/gp 96中的任一种一样有效，并且在某些情况下甚至可能更有效。将CRCL制剂与树突状细胞离体组合产生了一种细胞疫苗，可以在高比例的病例中根除预先存在的肿瘤。CRCL疫苗的高产率来自少量的起始材料，其采购的相对容易性和本文提供的功能数据表明，CRCL疫苗值得在试点临床试验癌症免疫治疗方案中进行评估。
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.