Immunotherapeutic potential of B7-DC (PD-L2) cross-linking antibody in conferring antitumor immunity (Retracted article. See vol. 70, pg. 9528, 2010)
Immunotherapeutic potential of B7-DC (PD-L2) cross-linking antibody in conferring antitumor immunity (Retracted article. See vol. 70, pg. 9528, 2010)
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DOI：
10.1158/0008-5472.can-03-3025
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发表时间：
2004-07-15
期刊：
影响因子：
11.2
通讯作者：
Pease, LR
中科院分区：
文献类型：
--
作者：
Radhakrishnan, S;Nguyen, LT;Pease, LR
天然存在的人抗体增强树突状细胞在交联B7-DC（PD-L2）上的功能，支持体外稳健的T细胞应答。此外，用B7-DC交联抗体处理树突状细胞导致白细胞介素-12的分泌，表明这种反应的TH1极化。在这里，我们使用免疫原性差的B16黑色素瘤肿瘤模型显示了这种B7-DC交联抗体的体内免疫抑制作用。在肿瘤细胞移植时用抗体全身性处理小鼠以CD4和CD8 T细胞依赖性方式防止肿瘤生长。B7-DC交联抗体处理的保护作用不依赖于内源性抗体应答。在用B7-DC交联抗体处理的动物中，可以从引流肿瘤部位的淋巴结中分离出肿瘤特异性CTL前体，但不能从用同种型对照抗体处理的动物中分离出。在体内引起的抗肿瘤反应是特异性的和持久的。更引人注目的是，在肺部建立肿瘤后，用B7-DC交联抗体治疗小鼠，以CD8-，穿孔素-和颗粒酶B-依赖的方式产生保护作用。自然杀伤细胞的耗竭并不能阻断B7-DC交联抗体治疗的效果。总之，这些发现表明，B7-DC与人IgM抗体sHIgM12交联可以诱导针对弱抗原性实验肿瘤的保护性免疫应答，因此具有作为治疗癌症的新型免疫方法的潜力。
A naturally occurring human antibody potentiates dendritic cell function on cross-linking B7-DC (PD-L2), supporting robust T-cell responses in vitro. Moreover, treatment of dendritic cells with B7-DC cross-linking antibody resulted in secretion of interieukin-12, suggesting a TH1 polarization of this response. Here we show an in vivo immunotherapeutic effect of this B7-DC cross-linking antibody using a poorly immunogenic B16 melanoma tumor model. Treatment of mice systemically with antibody at the time of tumor cell engraftment prevented tumor growth in a CD4 and CD8 T-cell-dependent manner. The protective effect of B7-DC crosslinking antibody treatment was independent of endogenous antibody responses. Tumor-specific CTL precursors could be isolated from lymph nodes draining the tumor site in animals treated with B7-DC cross-linking antibody, but not from those treated with isotype control antibodies. The elicited antitumor responses in vivo were specific and long-lasting. More strikingly, treatment of mice with B7-DC cross-linking antibody after the tumors were established in the lungs resulted in protection in a CD8-, perforin-, and granzyme B-dependent fashion. Depletion of natural killer cells did not block the effects of treatment with B7-DC cross-linking antibody. Together, these findings demonstrate that cross-linking B7-DC with the human IgM antibody sHIgM12 can induce a protective immune response against a weakly antigenic experimental tumor and therefore has potential as a novel immunotherapeutic approach for treating cancer.