Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian 350025, China.
Immunobiology. 2012 Jul;217(7):738-42. doi: 10.1016/j.imbio.2012.01.006. Epub 2012 Jan 10.
Previous evidence suggested that the stress protein grp170 can function as a highly efficient molecular chaperone, binding to large protein substrates and acting as a potent vaccine against specific tumors when purified from the same tumor. In addition, Pokemon can be found in almost all malignant tumor cells and is regarded to be a promising candidate for the treatment of tumors. However, the potential of the grp170-Pokemon chaperone complex has not been well described. In the present study, the natural chaperone complex between grp170 and the Pokemon was formed by heat shock, and its immunogenicity was detected by ELISPOT and (51)Cr-release assays in vitro and by tumor bearing models in vivo. Our results demonstrated that the grp170-Pokemon chaperone complex could elicit T cell responses as determined by ELISPOT and (51)Cr-release assays. In addition, immunized C57BL/6 mice were challenged with subcutaneous (s.c.) injection of Lewis cancer cells to induce primary tumors. Treatment of mice with the grp170-Pokemon chaperone complex also significantly inhibited tumor growth and prolonged the life span of tumor-bearing mice. Our results indicated that the grp170-Pokemon chaperone complex might represent a powerful approach to tumor immunotherapy and have significant potential for clinical application.
先前的证据表明，应激蛋白 grp170 可以作为一种高效的分子伴侣，当从同一肿瘤中纯化时，它可以与大的蛋白质底物结合，并作为针对特定肿瘤的有效疫苗。此外，Pokemon 几乎可以在所有恶性肿瘤细胞中找到，被认为是治疗肿瘤的有前途的候选物。然而，grp170-Pokemon 伴侣复合物的潜力尚未得到很好的描述。在本研究中，通过热休克形成 grp170 和 Pokemon 之间的天然伴侣复合物，并通过体外 ELISPOT 和 (51)Cr 释放测定以及体内荷瘤模型检测其免疫原性。我们的结果表明，grp170-Pokemon 伴侣复合物可以通过 ELISPOT 和 (51)Cr 释放测定来引发 T 细胞反应。此外，用 grp170-Pokemon 伴侣复合物免疫的 C57BL/6 小鼠通过皮下 (s.c.) 注射 Lewis 癌细胞来挑战，以诱导原发性肿瘤。用 grp170-Pokemon 伴侣复合物治疗小鼠还显著抑制了肿瘤生长并延长了荷瘤小鼠的寿命。我们的结果表明，grp170-Pokemon 伴侣复合物可能代表了一种强大的肿瘤免疫治疗方法，具有重要的临床应用潜力。
