Gong Jianlin, Koido Shigeo, Chen Dongshu, Tanaka Yasuhiro, Huang Lei, Avigan David, Anderson Kenneth, Ohno Tsuneya, Kufe Donald
Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Blood. 2002 Apr 1;99(7):2512-7. doi: 10.1182/blood.v99.7.2512.
Fusions of cancer cells and dendritic cells (DCs) are effective in the treatment of animal tumor models and patients with metastatic renal carcinoma. In this study, we have fused DCs with mouse 4TOO plasmacytoma cells. The results demonstrate that vaccination of mice with the fusion cells (FC/4TOO) is associated with induction of antitumor humoral and cytotoxic T lymphocyte (CTL) responses. Immunization with FC/4TOO cells protected mice against tumor challenge. In addition, treatment of established multiple myeloma with FC/4TOO cells was associated with prolongation of survival but not with eradication of disease. As interleukin (IL)-12 potentiates the induction of immune responses, recombinant mouse IL-12 was administered with the FC/4TOO vaccine. Treatment of mice with FC/4TOO and IL-12 was associated with increased CTL activity and T-cell proliferation responses. Treatment with FC/4TOO and IL-12 also resulted in eradication of established disease. These findings demonstrate that immunization with FC/4TOO fusion cells and IL-12 potentiates antitumor immunity and the treatment of murine multiple myeloma.
癌细胞与树突状细胞(DCs)的融合物在动物肿瘤模型及转移性肾癌患者的治疗中具有疗效。在本研究中,我们将DCs与小鼠4TOO浆细胞瘤细胞进行了融合。结果表明,用融合细胞(FC/4TOO)对小鼠进行疫苗接种与诱导抗肿瘤体液和细胞毒性T淋巴细胞(CTL)反应相关。用FC/4TOO细胞免疫可保护小鼠免受肿瘤攻击。此外,用FC/4TOO细胞治疗已建立的多发性骨髓瘤与生存期延长相关,但与疾病根除无关。由于白细胞介素(IL)-12可增强免疫反应的诱导,因此将重组小鼠IL-12与FC/4TOO疫苗联合使用。用FC/4TOO和IL-12治疗小鼠与CTL活性增加和T细胞增殖反应相关。用FC/4TOO和IL-12治疗还导致已建立的疾病被根除。这些发现表明,用FC/TOO融合细胞和IL-12进行免疫可增强抗肿瘤免疫力并治疗小鼠多发性骨髓瘤。