Bae Su-Mi, Kim Yong-Wan, Kwak Sun-Young, Kim Yong-Wook, Ro Duck-Yeong, Shin Jong-Chul, Park Choong-Hak, Han Sei-Jun, Oh Chung-Hun, Kim Chong-Kook, Ahn Woong-Shick
Cancer Research Institute, The Catholic University of Korea, Seoul 137-040, Korea.
Cancer Sci. 2007 May;98(5):747-52. doi: 10.1111/j.1349-7006.2007.00447.x.
Immunotherapy with photodynamic therapy (PDT) offers great promise as a new alternative for cancer treatment; however, its use remains experimental. In this study, we examined the immunotherapeutic significance of human papillomavirus (HPV)-immortalized tumor cell lysates induced by PDT with CpG-oligodeoxynucleotide (ODN). PDT-cell lysates were generated by irradiating Radachlorin (5 microg/mL) preloaded TC-1 cells carrying HPV 16 E7. PDT-cell lysates plus ODN coinjection for protection against E7-expressing tumors as well as specific immune responses were evaluated with the following tests: heat shock protein 70 (HSP70) enzyme-linked immunosorbent assay, in vitro and in vivo tumor growth inhibition, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) assay, cytotoxic T-lymphocyte assay, and fluorescence activated cell sorting (FACS) analysis. PDT-cell lysates plus ODN coinjection showed a significant suppression of tumor growth at both prophylactic and therapeutic levels, compared to PDT (or F/T)-cell lysates or ODN alone. In addition, we evaluated the level of the immune response with the coinjection. HSP70, an important regulator of inflammatory and immune response, was observed in abundance in the PDT-cell lysates. IFN-gamma production and cytotoxic T lymphocytes (CTL) responses were induced by PDT-cell lysates plus ODN injection. The coinjection resulted in PDT-cell lysate-specific antibodies (IgG1, IgG2a, IgG2b, and IgG3) and T-helper cell responses significantly higher than PDT-cell lysates alone. Moreover, IFN-gamma production and CTL responses were significantly induced in the PDT-cell lysate plus ODN immunized groups. These enhanced immune responses appeared to be mediated by CD8+ T cells only. These data suggest that PDT-cell lysates plus ODN injection may be an effective approach to induce CTL immune responses as a possible immunotherapeutic strategy for cancer therapy.
光动力疗法（PDT）免疫疗法作为一种癌症治疗的新选择具有很大前景；然而，其应用仍处于实验阶段。在本研究中，我们检测了用含CpG-寡脱氧核苷酸（ODN）的PDT诱导的人乳头瘤病毒（HPV）永生化肿瘤细胞裂解物的免疫治疗意义。通过照射预加载有HPV 16 E7的Radachlorin（5微克/毫升）的TC-1细胞来产生PDT细胞裂解物。通过以下试验评估PDT细胞裂解物加ODN共注射对表达E7肿瘤的保护作用以及特异性免疫反应：热休克蛋白70（HSP70）酶联免疫吸附测定、体外和体内肿瘤生长抑制、干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）测定、细胞毒性T淋巴细胞测定以及荧光激活细胞分选（FACS）分析。与单独的PDT（或F/T）细胞裂解物或ODN相比，PDT细胞裂解物加ODN共注射在预防和治疗水平上均显示出对肿瘤生长的显著抑制。此外，我们评估了共注射时的免疫反应水平。在PDT细胞裂解物中大量观察到HSP70，它是炎症和免疫反应的重要调节因子。PDT细胞裂解物加ODN注射诱导了IFN-γ产生和细胞毒性T淋巴细胞（CTL）反应。共注射导致PDT细胞裂解物特异性抗体（IgG1、IgG2a、IgG2b和IgG3）和T辅助细胞反应显著高于单独的PDT细胞裂解物。此外，在PDT细胞裂解物加ODN免疫组中显著诱导了IFN-γ产生和CTL反应。这些增强的免疫反应似乎仅由CD8 + T细胞介导。这些数据表明，PDT细胞裂解物加ODN注射可能是诱导CTL免疫反应的有效方法，作为一种可能的癌症治疗免疫治疗策略。
