Recombinant heat shock protein 70 in combination with radiotherapy as a source of tumor antigens to improve dendritic cell immunotherapy.

Recombinant heat shock protein 70 in combination with radiotherapy as a source of tumor antigens to improve dendritic cell immunotherapy.
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DOI:
10.3389/fonc.2012.00149
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发表时间:
2012
影响因子:
4.7
通讯作者:
Chi KH
Chi KH
中科院分区:
医学3区
文献类型:
--
作者:
Wang YS;Liu SJ;Huang SC;Chang CC;Huang YC;Fong WL;Chi MS;Chi KH

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局部放疗(RT)加瘤内树突状细胞(DC)注射可以介导免疫反应。我们假设联合注射外源重组热休克蛋白 70 (rHsp70) 与 RT-DC 可以与联合注射 HSP 肽一样有效地引发特异性免疫反应。 rHsp70-前列腺特异性抗原(rHSP70C'-PSA)和甲胎蛋白(rHSP70C'-AFP)用于比较特异性反应。在 CT26/PSA 和 CT26/AFP 小鼠模型上测量肿瘤生长抑制和全身抗肿瘤免疫反应。将 rHsp70 和 DC 瘤内共注射到受辐射的肿瘤部位,比单独注射 DC 诱导了更有效的抗肿瘤免疫反应。 rHsp70 在诱导肿瘤特异性细胞毒性 T 淋巴细胞反应或肿瘤生长延迟方面与 rHsp70C'-PSA 或 rHsp70C'-AFP 一样有效。这些结果表明,rHsp70和RT联合给药可能是实现RT-DC免疫治疗方案的简单有效的肿瘤抗原来源,并且易于在临床中应用。
Local radiotherapy (RT) plus intratumoral dendritic cell (DC) injection can mediate immunological response. We hypothesized that co-injection of exogenous recombinant heat shock protein 70 (rHsp70) in combination with RT-DC could be as effective as co-injection of HSP-peptide for evoking specific immune response. rHsp70-prostate-specific antigen (rHSP70C′-PSA) and α-fetoprotein (rHSP70C′-AFP) were used to compare specific response. Growth inhibition of the tumor and the systemic anti-tumor immune response were measured on CT26/PSA and CT26/AFP mice model. Intratumoral co-injection of rHsp70 and DC into the irradiated tumor site induced a more potent anti-tumor immune response than injection of DC alone. rHsp70 was as effective as rHsp70C′-PSA or rHsp70C′-AFP in inducing a tumor-specific cytotoxic T lymphocyte response or tumor growth delay. These results demonstrate that co-administration with rHsp70 and RT could be a simple and effective source of tumor antigens to achieve RT-DC immunotherapy protocol and easy to apply in clinical use.