A monoclonal antibody to O-acetyl-GD2 ganglioside and not to GD2 shows potent anti-tumor activity without peripheral nervous system cross-reactivity.
A monoclonal antibody to O-acetyl-GD2 ganglioside and not to GD2 shows potent anti-tumor activity without peripheral nervous system cross-reactivity.
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DOI：
10.1371/journal.pone.0025220
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Birklé S
中科院分区：
文献类型：
--
作者：
Alvarez-Rueda N;Desselle A;Cochonneau D;Chaumette T;Clemenceau B;Leprieur S;Bougras G;Supiot S;Mussini JM;Barbet J;Saba J;Paris F;Aubry J;Birklé S
抗GD 2神经节苷脂单克隆抗体（mAb）已被证明可有效治疗神经母细胞瘤。然而，由于抗GD 2 mAb与外周神经纤维结合，随后补体激活，有益作用与全身疼痛相关。表达GD 2的神经母细胞瘤细胞也表达其O-乙酰基衍生物O-乙酰基-GD 2神经节苷脂（OAcGD 2）。因此，我们使用mAb 8B 6研究了OAcGD 2在人体组织中的分布，以研究mAb 8B 6与人体组织的交叉反应性。使用免疫过氧化物酶技术在正常和恶性组织中进行OAcGD 2的分布。在体外和小鼠移植肿瘤模型中研究了mAb 8B 6的抗肿瘤特性。我们发现OAcGD 2不被周围神经纤维表达。此外，我们证明mAb 8B 6在体外和体内抑制肿瘤细胞生长方面非常有效。重要的是，mAb 8B 6抗肿瘤功效与特异于GD 2的mAb 14 G2 a的功效相当。开发特异于OAcGD 2的治疗性抗体可以提供具有减少的不良副作用的治疗选择，从而允许抗体的剂量递增。
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. 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. Development of therapeutic antibodies specific to OAcGD2 may offer treatment options with reduced adverse side effects, thereby allowing dose escalation of antibodies.
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影响因子：
20.3
作者：
Martinez, Caridad;Hofmann, Ted J.;Horwitz, Edwin M.
通讯作者：
Horwitz, Edwin M.
DOI：
10.1073/pnas.79.24.7629
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CAHAN, LD;IRIE, RF;PAULSON, JC
通讯作者：
PAULSON, JC
影响因子：
4.4
作者：
Kohla, G;Stockfleth, E;Schauer, R
通讯作者：
Schauer, R
DOI：
10.1084/jem.20021915
发表时间：
2002-12-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen HY;Varki A
通讯作者：
Varki A
影响因子：
158.5
作者：
Matthay, KK;Villablanca, JG;Reynolds, CP
通讯作者：
Reynolds, CP