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针对β-人绒毛膜促性腺激素两个表位的单克隆抗体用于癌症治疗。

Monoclonal antibodies to two epitopes of beta-human chorionic gonadotropin for the treatment of cancer.

作者信息

Iversen Patrick L, Mourich Dan V, Moulton Hong M

机构信息

AVI BioPharma Inc., 4575 SW Research Way, Corvallis, OR 97333, USA.

出版信息

Curr Opin Mol Ther. 2003 Apr;5(2):156-60.

Abstract

Human chorionic gonadotropin (hCG) is expressed by many histological types of cancer and may play an important role in tumor maintenance and progression. Vaccination of patients with the therapeutic peptide Avicine (CTP37; AVI BioPharma Inc/SuperGen Inc), that contains 37 amino acids from the carboxyl terminus (CTP37; AVI BioPharma Inc/SuperGen Inc) of hCG, can result in two distinct antibody responses to separate epitopes within the peptide. Colorectal cancer patients who develop both anti-hCG responses show a significant improvement in median survival time. These observations provide a compelling rationale for the development of two human monoclonal antibodies (mAbs), one for each of the epitopes within the 37 amino acid peptide region of hCG. Two such human mAbs, both exhibiting a high degree of specificity and affinity have been prepared using XenoMouse technology. These mAbs may prove useful in multiple clinical settings for the treatment of various cancers. Treatment options may include passive immunotherapy with both mAbs, mixed passive supplement to active specific immunotherapy with Avicine and conjugation of the mAbs with radioisotopes or cytotoxic drugs. The requirement for dual mAb therapy is consistent with current trends in the development of complex, non-toxic therapies for cancer.

摘要

人绒毛膜促性腺激素(hCG)在多种组织学类型的癌症中均有表达,可能在肿瘤维持和进展中发挥重要作用。用治疗性肽Avicine(CTP37;AVI生物制药公司/超级基因公司)对患者进行疫苗接种,该肽包含来自hCG羧基末端的37个氨基酸(CTP37;AVI生物制药公司/超级基因公司),可导致对该肽内不同表位产生两种不同的抗体反应。产生两种抗hCG反应的结直肠癌患者的中位生存时间有显著改善。这些观察结果为开发两种人单克隆抗体(mAb)提供了令人信服的理论依据,一种针对hCG的37个氨基酸肽区域内的每个表位。利用XenoMouse技术制备了两种这样的人mAb,它们均表现出高度的特异性和亲和力。这些mAb可能在多种临床环境中对治疗各种癌症有用。治疗选择可能包括两种mAb的被动免疫疗法、与Avicine的主动特异性免疫疗法的混合被动补充,以及mAb与放射性同位素或细胞毒性药物的偶联。双重mAb治疗的需求与目前开发复杂、无毒癌症治疗方法的趋势一致。

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