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瘤向的阿尔法颗粒疗法是用标记为actinium-225的碳酸无水酶IX抗体进行的

Katherine A Morgan¹, Christian W Wichmann^2,3,4, Laura D Osellame^2,3

¹School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne Melbourne Australia.

Chemical science

|March 1, 2024

概括

一种新的化剂,H2MacropaSqOEt,可以使用抗体进行癌症治疗,从而使动态-225 (225Ac) 的向输送成为可能. 这种方法在临床前模型中显示出显著的瘤减少.

科学领域:

放射性药物化学放射性药物化学
在瘤学瘤学.
生物结合化学的化学

背景情况:

使用actinium-225 (225Ac) 的向阿尔法疗法 (TAT) 在癌症治疗中显示出有前途.
有效地将225Ac传递给瘤需要强大的合剂,这些合剂可以与向抗体结合.
现有的化剂可能在稳定性或结合效率方面存在局限性.

研究的目的:

设计和合成一种新的双功能宏环合剂,H2MacropaSqOEt,用于抗体结合和225Ac复合.
评估H2MacropaSqOEt合剂与单克隆抗体吉伦图西马布 (hG250) 结合的特性.
在一个相关的癌症模型中评估得到的225Ac标记抗体结合物的治疗疗效.

主要方法:

合成H2MacropaSqOEt化剂,其中包括一个聚乙烯甘醇-方胺结合剂.
结合H2MacropaSqOEt与girentuximab (hG250) 的结合,以碳酸无水酶IX为向.
用225Ac对合物进行放射性标记,并评估人类血清中的复合稳定性.
在一只小鼠异种移植模型中评估治疗疗效的碳酸酶IX表达癌症.

主要成果:

化剂H2MacropaSqOEt成功合成并与hG250结合,化剂与抗体的比率为4:1,保持了抗体亲和力.
在室温下实现了对225Ac的结合物的定量和快速 (1分钟) 放射标记.
被标记为225Ac的抗体结合体在人血清中表现出极好的稳定性 (>7天).
在活体中观察到显著的瘤生长抑制在碳酸酶IX阳性异种移植模型中.

结论:

H2MacropaSqOEt是开发基于225Ac的向阿尔法疗法的通用化剂.
开发的抗体-化剂结合体显示出强大而稳定的瘤向和治疗效果.
这个平台为推进225Ac放射性药物用于癌症治疗提供了一个有前途的战略.

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