Cao X, Zhang W, He L, Xie Z, Ma S, Tao Q, Yu Y, Hamada H, Wang J
Department of Immunology, Second Military Medical University, Shanghai, People's Republic of China.
J Immunol. 1998 Dec 1;161(11):6238-44.
Dendritic cells (DC) are regarded as attractive candidates for cancer immunotherapy. Our aim is to improve the therapeutic efficacy of DC-based tumor vaccine by augmenting DC preferential chemotaxis on T cells. Mouse bone marrow-derived DC were transduced with lymphotactin (Lptn) gene by adenovirus vector. The supernatants from Lptn gene-modified DC (Lptn-DC) were capable of attracting CD4+ and CD8+ T cells in a chemotaxis assay, whereas their mock control could not. Lptn expression of Lptn-DC was further confirmed by RT-PCR. Lptn-DC were pulsed with Mut1 peptide and used for vaccination. Immunization with the low dose (1 x 10(4)) of Mut1 peptide-pulsed DC induced weak CTL activity, whereas the same amounts of Mut1 peptide-pulsed Lptn-DC markedly induced specific CTL against 3LL tumor cells. A single immunization with 1 x 10(4) Mut1 peptide-pulsed Lptn-DC could render mice resistant to a 5 x 10(5) 3LL tumor cell challenge completely, but their counterpart could not. The protective immunity induced by Mut1 peptide-pulsed Lptn-DC depends on both CD4+ T cells and CD8+ T cells rather than NK cells in the induction phase and depends on CD8+ T cells rather than CD4+ T cells and NK cells in the effector phase. Moreover, the involvement of CD28/CTLA4 costimulation pathway and IFN-gamma are also necessary. When 3LL tumor-bearing mice were treated with 1 x 10(4) Mut1 peptide-pulsed Lptn-DC, their pulmonary metastases were significantly reduced, whereas the same low dose of Mut1 peptide-pulsed DC had no obvious therapeutic effects. Our data suggest that Lptn-DC are more potent adjuvants for peptide delivery to induce protective and therapeutic antitumor immunity.
树突状细胞（DC）被视为癌症免疫治疗的有吸引力的候选者。我们的目标是通过增强DC对T细胞的优先趋化作用来提高基于DC的肿瘤疫苗的治疗效果。用腺病毒载体将lymphotactin（Lptn）基因转导至小鼠骨髓来源的DC。在趋化试验中，Lptn基因修饰的DC（Lptn-DC）的上清液能够吸引CD4 +和CD8 + T细胞，而其模拟对照则不能。通过RT-PCR进一步证实了Lptn-DC的Lptn表达。用Mut1肽脉冲Lptn-DC并用于疫苗接种。用低剂量（1×10⁴）的Mut1肽脉冲DC进行免疫诱导较弱的CTL活性，而相同量的Mut1肽脉冲Lptn-DC则明显诱导针对3LL肿瘤细胞的特异性CTL。用1×10⁴ Mut1肽脉冲Lptn-DC进行单次免疫可使小鼠完全抵抗5×10⁵ 3LL肿瘤细胞的攻击，但它们的对应物则不能。Mut1肽脉冲Lptn-DC诱导的保护性免疫在诱导阶段依赖于CD4 + T细胞和CD8 + T细胞而非NK细胞，在效应阶段依赖于CD8 + T细胞而非CD4 + T细胞和NK细胞。此外，CD28 / CTLA4共刺激途径和IFN-γ的参与也是必要的。当用1×10⁴ Mut1肽脉冲Lptn-DC治疗3LL荷瘤小鼠时，其肺转移明显减少，而相同低剂量的Mut1肽脉冲DC则没有明显的治疗效果。我们的数据表明，Lptn-DC是更有效的肽递送佐剂，可诱导保护性和治疗性抗肿瘤免疫。
