Sun X, Vale M, Leung E, Kanwar J R, Gupta R, Krissansen G W
Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Science, University of Auckland, Auckland, New Zealand.
Gene Ther. 2003 Sep;10(20):1728-34. doi: 10.1038/sj.gt.3302070.
Members of the B7 family costimulate the proliferation of lymphocytes during the initiation and maintenance of antigen-specific humoral and cell-mediated immune responses. While B7-1 and -2 are restricted to lymphoid tissues, and activate naïve T cells, recently identified members including B7-H2 and -H3 are widely expressed on nonlymphoid tissues, and regulate effector lymphocytes in the periphery. B7-H3 has properties that suggested it may display antitumor activity, including the ability to stimulate Th1 and cytotoxic T-cell responses. Here, we test this notion by determining whether intratumoral injection of an expression plasmid encoding a newly described mouse homologue of B7-H3 is able to eradicate EL-4 lymphomas. Intratumoral injection of a mouse B7-H3 pcDNA3 expression plasmid led to complete regression of 50% tumors, or otherwise significantly slowed tumor growth. Mice whose tumors completely regressed resisted a challenge with parental tumor cells, indicating systemic immunity had been generated. B7-H3-mediated antitumor immunity was mediated by CD8(+) T and NK cells, with no apparent contribution from CD4(+) T cells. In summary, the results indicate that B7-H3 interactions may play a role in regulating cell-mediated immune responses against cancer, and that B7-H3 is a potential therapeutic tool.
B7家族成员在抗原特异性体液免疫和细胞介导的免疫反应的启动和维持过程中共同刺激淋巴细胞的增殖。虽然B7-1和B7-2局限于淋巴组织，并激活幼稚T细胞，但最近发现的成员包括B7-H2和B7-H3在非淋巴组织中广泛表达，并在外周调节效应淋巴细胞。B7-H3具有一些特性，提示它可能具有抗肿瘤活性，包括刺激Th1和细胞毒性T细胞反应的能力。在这里，我们通过确定瘤内注射编码新描述的B7-H3小鼠同源物的表达质粒是否能够根除EL-4淋巴瘤来验证这一观点。瘤内注射小鼠B7-H3 pcDNA3表达质粒导致50%的肿瘤完全消退，否则显著减缓肿瘤生长。肿瘤完全消退的小鼠对亲本肿瘤细胞的攻击具有抵抗力，表明已产生全身免疫。B7-H3介导的抗肿瘤免疫由CD8(+) T细胞和NK细胞介导，CD4(+) T细胞没有明显作用。总之，结果表明B7-H3相互作用可能在调节针对癌症的细胞介导免疫反应中起作用，并且B7-H3是一种潜在的治疗工具。
