Xu Feng, Ye Ying-Jiang, Liu Wei, Kong Meng, He Yu, Wang Shan
Department of Gastroenterological Surgery, Surgical Oncology Laboratory, Peking University People's Hospital, Beijing, China.
Scand J Gastroenterol. 2010 Jun;45(6):707-13. doi: 10.3109/00365521003650180.
Colorectal cancer (CRC) is one of the most common malignancies in the western world. More than 60% among patients will develop liver metastases. Although surgical resection is the first choice worldwide, at this point an effective approach for the treatment of patients with liver metastasis and cancer recurrence postoperation has not yet been found. The aim of this study is to investigate the role of the allogeneic dendritomas from fusion of DCs and metastatic colon cancer cells in the activation of anti-tumor immunity against colorectal cancer liver metastases.
Hybrids were generated by fused allogeneic human peripheral blood dendritic cells with metastatic colon cancer SW620 cells using 50% polyethylene glycol (PEG). Induction of immune responses was assessed by ex vivo ELISPOT assays. A murine model of CRC liver metastasis was used by intrasplenic injection. The validity of the vaccine was observed by Vaccination CRC liver metastasis murine model with DC/tumor hybrids.
The hybrids highly express the major molecules of DCs and tumor cells. The number of hybrids pulsed CTL secreting IFN-gamma was significantly higher when compared to the DC controls (p < 0.01). In a therapeutic setting mice vaccinated with in vitro cultured hybrids produced strong cellular immune responses and significant inhibition of tumor growth, compared to sham vaccinated controls.
Vaccination with hybrids can induces strong cellular responses and significant protection from challenge in SCID mouse metastatic CRC model.
结直肠癌(CRC)是西方世界最常见的恶性肿瘤之一。超过60%的患者会发生肝转移。尽管手术切除是全球首选的治疗方法,但目前尚未找到治疗肝转移和术后癌症复发患者的有效方法。本研究的目的是探讨树突状细胞(DCs)与转移性结肠癌细胞融合产生的同种异体树突状瘤在激活针对结直肠癌肝转移的抗肿瘤免疫中的作用。
使用50%聚乙二醇(PEG)将同种异体人外周血树突状细胞与转移性结肠癌细胞SW620融合,产生杂交细胞。通过体外酶联免疫斑点分析(ELISPOT)评估免疫反应的诱导情况。通过脾内注射建立结直肠癌肝转移的小鼠模型。用DC/肿瘤杂交细胞接种结直肠癌肝转移小鼠模型,观察疫苗的有效性。
杂交细胞高度表达DCs和肿瘤细胞的主要分子。与DC对照组相比,用杂交细胞刺激的分泌γ干扰素的细胞毒性T淋巴细胞(CTL)数量显著更高(p < 0.01)。在治疗组中,与假接种对照组相比,接种体外培养杂交细胞的小鼠产生了强烈的细胞免疫反应,并显著抑制了肿瘤生长。
在严重联合免疫缺陷(SCID)小鼠转移性结直肠癌模型中,接种杂交细胞可诱导强烈的细胞反应,并对攻击产生显著的保护作用。