Mody Avani A, Mukthavaram Rajesh, Jiang Pengfei, Gangangari Kishore, Pillarsetty Nagavarakishore, Kesari Pranav R, Padul Vijay, Kesari Sneha L, Rahbarlayegh Elnaz, Glassy Mark C, Kesari Santosh
CureScience Institute, San Diego, CA, USA.
Translational Neuro-Oncology Laboratory, University of California, San Diego, Moores Cancer Center, La Jolla, CA, USA.
Sci Rep. 2025 Mar 25;15(1):10178. doi: 10.1038/s41598-025-95360-9.
Pritumumab is a human IgG1 kappa antibody that targets ecto-domain vimentin (EDV) which is overexpressed in several malignant tumors including glioblastomas. To understand preclinical biological activity and safety of pritumumab derived from Chinese hamster ovary (CHO) cells, we evaluated tumor targeting ability, brain-tumor barrier permeability, growth inhibition, and primate safety studies. In-vivo and ex-vivo imaging studies demonstrate pritumumab to cross the blood brain/blood tumor barrier and an Zr-labeled pritumumab immunoconjugate showed the antibody specifically targeted tumor cells. In mouse xenograft models, pritumumab inhibited the growth of U251 glioblastoma and PANC-1 pancreatic cancer cells. A 29-day intravenous toxicology study in cynomolgus monkeys was carried out to analyze the safety and toxicity of pritumumab, and no toxic effects were observed. Overall, these data together suggest pritumumab is biologically active and animal models can be used to further understand the various functions of the antibody. Clinical trials in brain cancer patients assessing safety and efficacy of pritumumab as a therapeutic for brain cancer are in process.
普立妥单抗是一种人IgG1κ抗体，靶向波形蛋白胞外结构域（EDV），该结构域在包括胶质母细胞瘤在内的多种恶性肿瘤中过表达。为了解源自中国仓鼠卵巢（CHO）细胞的普立妥单抗的临床前生物学活性和安全性，我们评估了其肿瘤靶向能力、血脑/血肿瘤屏障通透性、生长抑制以及灵长类动物安全性研究。体内和体外成像研究表明普立妥单抗可穿过血脑/血肿瘤屏障，并且一种锆标记的普立妥单抗免疫偶联物显示该抗体可特异性靶向肿瘤细胞。在小鼠异种移植模型中，普立妥单抗抑制了U251胶质母细胞瘤和PANC - 1胰腺癌细胞的生长。对食蟹猴进行了一项为期29天的静脉毒理学研究，以分析普立妥单抗的安全性和毒性，未观察到毒性作用。总体而言，这些数据共同表明普立妥单抗具有生物学活性，并且动物模型可用于进一步了解该抗体的各种功能。评估普立妥单抗作为脑癌治疗药物的安全性和有效性的脑癌患者临床试验正在进行中。
