R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan; Department of Pediatric Surgery, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Biochem Biophys Res Commun. 2018 Sep 10;503(3):1666-1673. doi: 10.1016/j.bbrc.2018.07.097. Epub 2018 Jul 24.
The mechanism underlying the spontaneous regression of neuroblastoma is unclear. Although it was hypothesized that this regression occurs via an immunological mechanism, there is no clinical evidence, and no animal models have been developed to investigate the involvement of immune systems, especially natural antibodies, against neuroblastoma. We performed an immunological analysis of homo- and heterozygous TH-MYCN transgenic mice as a model of aggressive neuroblastoma. Mice with no or small (<5 mm) tumors showed higher antibody titers in plasma than mice with large (>5 mm) tumors. A significant negative correlation was observed between the tumor diameter and the titer of antitumor antibody. This antibody had complement-dependent cytotoxicity but not antibody-dependent cellular cytotoxicity against neuroblastoma cells. Moreover, B-cell depletion had no effect on the tumor incidence in vivo. We revealed that TH-MYCN transgenic mice have a natural antibody against neuroblastoma that correlate with tumor size. However, this antibody does not correlate with the spontaneous regression of neuroblastoma. Thus, the function of the natural antibody is limited.
神经母细胞瘤自发消退的机制尚不清楚。虽然有人假设这种消退是通过免疫机制发生的，但目前尚无临床证据，也没有开发出动物模型来研究免疫系统的参与，特别是针对神经母细胞瘤的天然抗体。我们对同型和异型 TH-MYCN 转基因小鼠进行了免疫分析，作为侵袭性神经母细胞瘤的模型。无肿瘤或肿瘤较小（<5mm）的小鼠的血浆抗体滴度高于肿瘤较大（>5mm）的小鼠。肿瘤直径与抗肿瘤抗体滴度之间存在显著的负相关。该抗体对神经母细胞瘤细胞具有补体依赖性细胞毒性，但不具有抗体依赖性细胞毒性。此外，B 细胞耗竭对体内肿瘤发生率没有影响。我们揭示了 TH-MYCN 转基因小鼠具有针对神经母细胞瘤的天然抗体，且与肿瘤大小相关。然而，这种抗体与神经母细胞瘤的自发消退无关。因此，天然抗体的功能有限。
