Study of the Antiproliferative Activity of a Humanized Antibody to the Cancer-Testis Antigen PRAME

IF 1.7 4区化学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Russian Journal of Bioorganic Chemistry Pub Date : 2025-09-28 DOI:10.1134/S1068162025603799

M. V. Larina, Yu. P. Finashutina, N. A. Kravchuk, V. A. Misyurin, V. N. Novoseletsky, D. S. Balabashin, O. N. Solopova, D. V. Sokolova, V. S. Pokrovsky, D. A. Dolgikh, T. K. Aliev, A. V. Misyurin, M. P. Kirpichnikov

{"title":"Study of the Antiproliferative Activity of a Humanized Antibody to the Cancer-Testis Antigen PRAME","authors":"M. V. Larina, Yu. P. Finashutina, N. A. Kravchuk, V. A. Misyurin, V. N. Novoseletsky, D. S. Balabashin, O. N. Solopova, D. V. Sokolova, V. S. Pokrovsky, D. A. Dolgikh, T. K. Aliev, A. V. Misyurin, M. P. Kirpichnikov","doi":"10.1134/S1068162025603799","DOIUrl":null,"url":null,"abstract":"Objective: The PRAME antigen (Preferentially Expressed Antigen in Melanoma), a cancer-testis antigen expressed in various tumor types, represents an attractive target for targeted cancer therapy. Methods: A humanized antibody (6H8Hu) was developed based on the monoclonal antibody 6H8 specific to the PRAME protein. The antibody was produced in CHO cells. Results and Discussion: The humanized antibody retains the high affinity of the parental mAb to the antigen (1.2 nM), binds to both recombinant and native PRAME protein, inhibits the proliferation of the PRAME-positive human melanoma cell line Mel Ibr, and suppresses tumor nodule growth in vivo to a degree comparable to that of the murine antibody 6H8 and the cytostatic agent melphalan. Conclusions: The humanized antibody 6H8Hu is a promising candidate for targeted therapy against PRAME-positive melanoma, showing potential comparable to murine antibodies and conventional cytotoxic treatments.","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2089 - 2099"},"PeriodicalIF":1.7000,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Russian Journal of Bioorganic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1134/S1068162025603799","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: The PRAME antigen (Preferentially Expressed Antigen in Melanoma), a cancer-testis antigen expressed in various tumor types, represents an attractive target for targeted cancer therapy. Methods: A humanized antibody (6H8Hu) was developed based on the monoclonal antibody 6H8 specific to the PRAME protein. The antibody was produced in CHO cells. Results and Discussion: The humanized antibody retains the high affinity of the parental mAb to the antigen (1.2 nM), binds to both recombinant and native PRAME protein, inhibits the proliferation of the PRAME-positive human melanoma cell line Mel Ibr, and suppresses tumor nodule growth in vivo to a degree comparable to that of the murine antibody 6H8 and the cytostatic agent melphalan. Conclusions: The humanized antibody 6H8Hu is a promising candidate for targeted therapy against PRAME-positive melanoma, showing potential comparable to murine antibodies and conventional cytotoxic treatments.

Abstract Image

查看原文本刊更多论文

癌睾丸抗原PRAME人源化抗体抗增殖活性的研究

目的：PRAME抗原（黑色素瘤优先表达抗原）是一种在多种肿瘤类型中表达的癌睾丸抗原，是肿瘤靶向治疗的一个有吸引力的靶点。方法：以PRAME蛋白特异性单克隆抗体6H8为基础，制备人源化抗体6H8Hu。抗体在CHO细胞中产生。结果和讨论：人源化抗体保留了亲本单抗对抗原（1.2 nM）的高亲和力，与重组PRAME蛋白和天然PRAME蛋白结合，抑制PRAME阳性的人黑色素瘤细胞系Mel Ibr的增殖，抑制肿瘤瘤瘤生长的程度与小鼠抗体6H8和细胞抑制剂melphalan相当。结论：人源化抗体6H8Hu是一种有希望的靶向治疗prame阳性黑色素瘤的候选抗体，显示出与小鼠抗体和传统细胞毒治疗相当的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Russian Journal of Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

1.80

自引率

10.00%

发文量

118

审稿时长

3 months

期刊介绍： Russian Journal of Bioorganic Chemistry publishes reviews and original experimental and theoretical studies on the structure, function, structure–activity relationships, and synthesis of biopolymers, such as proteins, nucleic acids, polysaccharides, mixed biopolymers, and their complexes, and low-molecular-weight biologically active compounds (peptides, sugars, lipids, antibiotics, etc.). The journal also covers selected aspects of neuro- and immunochemistry, biotechnology, and ecology.