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创胜集团, 生物药, 抗体, 药物研发

创胜集团 - 全整合型国际化生物制药公司

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学术论文及会议壁报

[177Lu] Lu标记的抗Claudin18.2抗体在胃癌小鼠异种移植模型中展现出放射免疫治疗潜力

14 Dec, 2023

Authors: 

Ziqing Zeng1 · Liqiang Li1 · Jinping Tao1 · Jiayue Liu1 · Hongjun Li2 · Xueming Qian2 · Zhi Yang1 · Hua Zhu1

Purpose:

Gastric cancer (GC), one of the most prevalent and deadliest tumors worldwide, is often diagnosed at an advanced stage with limited treatment options and poor prognosis. The development of a CLDN18.2-targeted radioimmunotherapy probe is a potential treatment option for GC.
Methods: 

The CLDN18.2 antibody TST001 (provided by Transcenta) was conjugated with DOTA and radiolabeled with the radioactive nuclide 177Lu. The specificity and targeting ability were evaluated by cell uptake, imaging and biodistribution experiments. In BGC823CLDN18.2/AGSCLDN18.2 mouse models, the efficacy of [177Lu]Lu-TST001 against CLDN18.2- expressing tumors was demonstrated, and toxicity was evaluated by H&E staining and blood sample testing.

Results: 

[177Lu]Lu-TST001 was labeled with an 99.17%±0.32 radiochemical purity, an 18.50±1.27 MBq/nmol specific activity and a stability of ≥94% after 7 days. It exhibited specific and high tumor uptake in CLDN18.2-positive xenografts of GC mouse models. Survival studies in BGC823CLDN18.2 and AGSCLDN18.2 tumor-bearing mouse models indicated that a low dose of 5.55 MBq and a high dose of 11.10 MBq [177Lu]Lu-TST001 significantly inhibited tumor growth compared to the saline control group, with the 11.1 MBq group showing better therapeutic efficacy. Histological staining with hematoxylin and eosin (H&E) and Ki67 immunohistochemistry of residual tissues confirmed tumor tissue destruction and reduced tumor cell proliferation following treatment. H&E showed that there was no significant short-term toxicity observed in the heart, spleen, stomach or other important organs when treated with a high dose of [177Lu]Lu-TST001, and no apparent hematotoxicity or liver toxicity was observed.