Centre de Recherche en Cancérologie de Nantes Angers, Inserm, Université de Nantes, Nantes Atlantique Universités, U892, France.
PLoS One. 2011;6(9):e25220. doi: 10.1371/journal.pone.0025220. Epub 2011 Sep 22.
Monoclonal antibodies (mAb) against GD2 ganglioside have been shown to be effective for the treatment of neuroblastoma. Beneficial actions are, however, associated with generalized pain due to the binding of anti- GD2 mAbs to peripheral nerve fibers followed by complement activation. Neuroblastoma cells that express GD2 also express its O-acetyl derivative, O-acetyl- GD2 ganglioside (OAcGD2). Hence, we investigated the distribution of OAcGD2 in human tissues using mAb 8B6 to study the cross-reactivity of mAb 8B6 with human tissues.
METHODOLOGY/PRINCIPAL FINDINGS: The distribution of OAcGD2 was performed in normal and malignant tissues using an immunoperoxydase technique. Anti-tumor properties of mAb 8B6 were studied in vitro and in vivo in a transplanted tumor model in mice. We found that OAcGD2 is not expressed by peripheral nerve fibers. Furthermore, we demonstrated that mAb 8B6 was very effective in the in vitro and in vivo suppression of the growth of tumor cells. Importantly, mAb 8B6 anti-tumor efficacy was comparable to that of mAb 14G2a specific to GD2.
CONCLUSION/SIGNIFICANCE: Development of therapeutic antibodies specific to OAcGD2 may offer treatment options with reduced adverse side effects, thereby allowing dose escalation of antibodies.
针对 GD2 神经节苷脂的单克隆抗体（mAb）已被证明对神经母细胞瘤的治疗有效。然而，有益的作用与抗 GD2 mAb 与外周神经纤维结合，随后补体激活引起的全身性疼痛有关。表达 GD2 的神经母细胞瘤细胞也表达其 O-乙酰衍生物，O-乙酰-GD2 神经节苷脂（OAcGD2）。因此，我们使用 mAb 8B6 研究 OAcGD2 在人组织中的分布，以研究 mAb 8B6 与人组织的交叉反应性。
方法/主要发现：使用免疫过氧化物酶技术在正常和恶性组织中进行 OAcGD2 的分布。在体外和小鼠移植肿瘤模型中研究 mAb 8B6 的抗肿瘤特性。我们发现 OAcGD2 不由外周神经纤维表达。此外，我们证明 mAb 8B6 非常有效地抑制肿瘤细胞的体外和体内生长。重要的是，mAb 8B6 的抗肿瘤疗效与针对 GD2 的 mAb 14G2a 相当。
结论/意义：开发针对 OAcGD2 的治疗性抗体可能提供副作用减少的治疗选择，从而允许抗体剂量增加。
