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    • 9. 发明申请
    • AGENT OF HUMAN ORIGIN FOR VACCINATION AGAINST GD2 POSITIVE TUMOURS
    • 资源人力来源反对接种GD2阳性肿瘤
    • WO02087611B1
    • 2004-03-04
    • PCT/DE0104359
    • 2001-11-22
    • FISCHER PETERUTTENREUTHER-FISCHER MARTINA MKRUEGER JOERG
    • FISCHER PETERUTTENREUTHER-FISCHER MARTINA MKRUEGER JOERG
    • C07K16/42A61K39/395
    • C07K16/4241A61K2039/505C07K2317/24C07K2317/55
    • Studies using monoclonal antibodies against the disialoganglioside GD2 in tumours of neuroectodermal origin, such as neuroblastoma, melanoma and small-cell lung carcinoma have shown that immunisation against tumour-associated antigens is probably necessary to obtain therapeutic long-term effects. Direct vaccination with GD2 is therapeutically unsuitable owing to difficulties of purification, poor water solubility and low immunogenity. Antiidiotypic antibodies (anti-Ids) could be used as a replacement against anti-GD2 antibodies, said antiidiotypic antibodies imitating GD2 in such a way that they act immunogenically against GD2. The anti-Ids against GD2 antibodies used in previous studies are only sub-optimally suitable for the therapy as a result of their murine origin. Human anti-Ids, currently produced using the EBV-hybridoma technique have not been used in commercial, therapeutic applications notably because of their instability. The aim of the invention is therefore to clone stable anti-Ids of human origin against GD2 antibodies, using recombinant techniques (phage display). Said anti-Ids can be used as medicaments for the treatment of (GD2) positive tumours and in the associated diagnostics. The presence of recombinant Fab with a known sequence allows the optimal preparation of the vaccines as a fusion protein or DNA vaccines.
    • 在神经外胚层来源的肿瘤,例如成神经细胞瘤,黑色素瘤和小细胞肺癌靠在disialoganglioside GD2的单克隆抗体的研究表明,对于长期的治疗效果可能是针对肿瘤相关抗原的免疫是必要的。 与GD2直接接种是水溶性差和低免疫原性的治疗,因为难以纯化的不适合的。 作为替代抗独特型抗体(anti-ID)可以对任何模仿GD2,让他们采取行动反对GD2免疫抗GD2抗体使用。 先前在临床试验中的抗IDS对GD2阿克使用的是小于最佳适合用于治疗的鼠来源。 先前由EBV /杂交瘤产生具有人抗IDS,除其他外, 因为不稳定的不是商业,治疗使用中发现。 因此,本发明是基于在对象上,以通过重组技术(噬菌体展示)稳定的防IDS对GD2阿克人源中克隆。 这些被发现作为(GD2)阳性肿瘤的治疗药物和在随附的诊断应用程序。 已知序列的重组的Fab的存在允许疫苗的最佳制备为融合蛋白或DNA疫苗。