四种多肽负载的自体树突状细胞治疗恶性黑色素瘤近期疗效观察

Evaluation of the Curative Effect in the Near Future of the Dendritic Cells Pulsed with Four Polypeptide in the Treatment of Malignant Melanoma

目的探讨MAGE-3、Tyrosinase、MART-1、Gp-100等4种多肽负载的自体树突状细胞(DCs)治疗恶性黑素素瘤的安全性和近期疗效。方法分离患者外周血单核细胞,用重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)和白细胞介素-4(rhIL-4)体外诱导DCs,MAGE-3、tyrosinase、MART-1、Gp-100等4种多肽负载自体DCs,对10例HLA-A2阳性的恶性黑色素瘤患者进行4次DCs免疫治疗,观察其安全性、免疫功能和临床疗效。结果治疗中未出现明显不良反应,治疗后血清中IL-2、IL-12和IFN-γ水平呈明显上升趋势(P<0.05),6例患者的DTH检测阳性;7例有淋巴结转移的患者中,2例淋巴结转移消失,2例淋巴结肿大减小,3例淋巴结肿大稳定。结论多肽负载的自体DCs治疗恶性黑色素瘤可改善患者的免疫功能,激发特异性免疫反应,缓解病情,且不良反应少,为恶性黑色素瘤的免疫治疗提供了一条新途径。

Objective To evaluate the safety and curative effect in the near future of the dendritic cells（DCs） pulsed with four polypeptide （MAGE-3, Tyrosinase, MART-1 and Gp-100） in the treatment of malignant melanoma. Methods Mononuelear cells were isolated from the peripheral blood of 10 malig- nant melanoma patients. The DCs pulsed with four nona peptide（ MAGE-3, tyrosinase, MART-1 and Gp- 100） were induced in vitro with rhGM-CSF and rhIL-4. The 10 HLA-A2-positive patients were treated with DCs for four times, and the safety, immunological function and clinical effect were observed. Results No severe adverse reaction was observed. The levels of IL-2, IL-12 and IFN-γ in the serum of patients rised significantly after the treatment. DTH test was positive in 6 patents. Of the 7 patients with lymph nodes metastasis, complete remission of the lymph nodes was observed in 2 patients, shrinkage in 2 patients and stabilization in 3 patients. Conclusion Treatment of malignant melanoma with DCs pulsed with polypeptide could improve the immunological function of the patients, stimulate specific immune response and modify symptoms with rare adverse reactions, and provide a new immunotherapy approach for treatment of malignant melanoma.