Division of Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
Int J Oncol. 2011 Oct;39(4):907-13. doi: 10.3892/ijo.2011.1124. Epub 2011 Jul 14.
This study demonstrates the ability to generate antigen-specific cytotoxic T cells (CTLs) against HER2 using a xenoantigenic immune stimulation strategy. Dendritic cells (DCs) were transduced with an adenovirus vector incorporating full-length cDNA for rat (xenoantigen) epidermal growth factor receptor 2 (Adv-HER2). Stimulation of autologous T cells with Adv-HER2 infected DCs led to enhanced HER2-specific reactivity as assessed by quantitative real-time polymerase chain reaction (qRT-PCR) for T cell IFN-γ mRNA. In ELISPOT and intracellular cytokine staining (ICS) assays, CD8+ CTLs induced by Adv-HER2 transduced DCs released IFN-γ following stimulation with irradiated autologous DCs infected with Adv-HER2 or loaded with a human prostate cancer cell line (LNCaP) lysate. DCs pulsed with HER2 peptides were less stimulatory than Adv-HER2 transduced DCs. HER2 DC induced CTL lysed HER2+ HLA-A2+ tumor cells (MCF-7); significantly reduced lysis occurred in HER2+ HLA-A2- tumor cells (SKOV-3), and the NK cell sensitive cell line K-562.
本研究展示了使用异种抗原免疫刺激策略产生针对 HER2 的抗原特异性细胞毒性 T 细胞 (CTL) 的能力。树突状细胞 (DC) 被携带全长大鼠 (异种抗原) 表皮生长因子受体 2 cDNA 的腺病毒载体转导。用 Adv-HER2 感染的 DC 刺激自体 T 细胞，通过定量实时聚合酶链反应 (qRT-PCR) 检测 T 细胞 IFN-γ mRNA，评估增强的 HER2 特异性反应。在 ELISPOT 和细胞内细胞因子染色 (ICS) 测定中，用 Adv-HER2 感染的辐照自体 DC 或负载人前列腺癌细胞系 (LNCaP) 裂解物刺激后，由 Adv-HER2 转导的 DC 诱导的 CD8+CTL 释放 IFN-γ。用 HER2 肽脉冲处理的 DC 比 Adv-HER2 转导的 DC 刺激作用小。HER2 DC 诱导 CTL 裂解 HER2+HLA-A2+肿瘤细胞 (MCF-7)；在 HER2+HLA-A2-肿瘤细胞 (SKOV-3) 和 NK 细胞敏感细胞系 K-562 中，明显减少了裂解。
