Zhang W, He L, Cao X
Department of Immunology, Second Military Medical University, Shanghai 200433.
Zhonghua Yi Xue Za Zhi. 1999 Mar;79(3):170-3.
To evaluate the potent effects of lymphotactin on tumor immunogene therapy and to improve the therapeutic efficacy of dendritic cells (DCs)-based vaccine, the protective and therapeutic effects of tumor antigen peptide-pulsed lymphotactin gene-modified dendritic cells were investigated.
In the tumor model of 3LL Lewis lung carcinoma, mouse bone marrow DCs transduced with mouse lymphotactin gene by adenovirus vector (Ltn-DC) were pulsed with MHC-I-restricted, 3LL cell-specific tumor peptide Mut 1 (FEQNTAQP), and used to vaccinate syngeneic mice or to treat the preestablished tumor-bearing mice with spontaneous pulmonary metastases.
Immunization with Mut 1 peptide-pulsed Ltn-DC induced specific CTL against 3LL cells and induced protective antitumor immunity, which rendered the immunized mice resistant completely to 3LL tumor challenge. In vivo depletion of immune cell subsets with mAbs demonstrated that the protective immunity induced by Mut1 peptide-pulsed Ltn-DC in the induction phase was dependent on both CD4+ T cells and CD8+ T cells rather than NK cells, and in the effector phase on CD8+ T cells rather than CD4+ T cells or NK cells. CD28/CTLA4 pathway of T cell costimulation and IFN-gamma were also necessary for induction of antitumor immunity by Ltn-DC pulsed with Mut1 peptide. Treatment with Mut1 peptide-pulsed Ltn-DC significantly inhibited the 3LL spontaneous pulmonary metastases of the preestablished tumor-bearing mice and exhibited obvious therapeutic effects.
Our data suggest that Ltn gene modified DCs are more potent in the induction of protective and therapeutic antitumor immunity through the preferential chemotaxis of DCs on T cells. Vaccination with tumor antigen-pulsed Ltn-DC may be a novel approach to immunotherapy of cancer.
为评估淋巴细胞趋化因子对肿瘤免疫基因治疗的显著作用并提高基于树突状细胞（DCs）的疫苗的治疗效果，研究了肿瘤抗原肽脉冲淋巴细胞趋化因子基因修饰的树突状细胞的保护和治疗作用。
在3LL Lewis肺癌肿瘤模型中，用腺病毒载体将小鼠淋巴细胞趋化因子基因转导至小鼠骨髓DCs（Ltn-DC），用MHC-I限制性的、3LL细胞特异性肿瘤肽Mut 1（FEQNTAQP）进行脉冲处理，用于给同基因小鼠接种疫苗或治疗已建立的伴有自发性肺转移的荷瘤小鼠。
用Mut 1肽脉冲Ltn-DC免疫诱导了针对3LL细胞的特异性CTL并诱导了保护性抗肿瘤免疫，使免疫小鼠完全抵抗3LL肿瘤攻击。用单克隆抗体在体内清除免疫细胞亚群表明，Mut1肽脉冲Ltn-DC在诱导期诱导的保护性免疫依赖于CD4+ T细胞和CD8+ T细胞而非NK细胞，在效应期依赖于CD8+ T细胞而非CD4+ T细胞或NK细胞。T细胞共刺激的CD28/CTLA4途径和IFN-γ对于用Mut1肽脉冲的Ltn-DC诱导抗肿瘤免疫也是必需的。用Mut1肽脉冲Ltn-DC治疗显著抑制了已建立的荷瘤小鼠的3LL自发性肺转移并显示出明显的治疗效果。
我们的数据表明，Ltn基因修饰的DCs通过DCs对T细胞的优先趋化作用在诱导保护性和治疗性抗肿瘤免疫方面更有效。用肿瘤抗原脉冲Ltn-DC接种疫苗可能是一种新型的癌症免疫治疗方法。
