Academic Journal
Preclinical imaging evaluation of a bispecific antibody targeting hPD1/CTLA4 using humanized mice
| العنوان: | Preclinical imaging evaluation of a bispecific antibody targeting hPD1/CTLA4 using humanized mice |
|---|---|
| المؤلفون: | Xingguo Hou, Song Liu, Ziqing Zeng, Zilei Wang, Jin Ding, Yan Chen, Xiangyu Gao, Jianghua Wang, Guanxi Xiao, Baiyong Li, Hua Zhu, Zhi Yang |
| المصدر: | Biomedicine & Pharmacotherapy, Vol 175, Iss , Pp 116669- (2024) |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2024 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Bispecific antibody, Cadonilimab, Programmed death molecule 1, Cytotoxic T-lymphocyte-associated protein 4, Immuno-PET imaging, Therapeutics. Pharmacology, RM1-950 |
| الوصف: | Background: The lack of an efficient way to screen patients who are responsive to immunotherapy challenges PD1/CTLA4-targeting cancer treatment. Immunotherapeutic efficacy cannot be clearly determined by peripheral blood analyses, tissue gene markers or CT/MR value. Here, we used a radionuclide and imaging techniques to investigate the novel dual targeted antibody cadonilimab (AK104) in PD1/CTLA4-positive cells in vivo. Methods: First, humanized PD1/CTLA4 mice were purchased from Biocytogen Pharmaceuticals (Beijing) Co., Ltd. to express hPD1/CTLA4 in T-cells. Then, mouse colon cancer MC38-hPD-L1 cell xenografts were established in humanized mice. A bispecific antibody targeting PD1/CTLA4 (AK104) was labeled with radio-nuclide iodine isotopes. Immuno-PET/CT imaging was performed using a bispecific monoclonal antibody (mAb) probe 124I-AK104, developed in-house, to locate PD1+/CTLA4+ tumor-infiltrating T cells and monitor their distribution in mice to evaluate the therapeutic effect. Results: The 124I-AK104 dual-antibody was successfully constructed with ideal radiochemical characteristics, in vitro stability and specificity. The results of immuno-PET showed that 124I-AK104 revealed strong hPD1/CTLA4-positive responses with high specificity in humanized mice. High uptake of 124I-AK104 was observed not only at the tumor site but also in the spleen. Compared with PD1- or CTLA4-targeting mAb imaging, 124I-AK104 imaging had excellent standard uptake values at the tumor site and higher tumor to nontumor (T/NT) ratios. Conclusions: The results demonstrated the potential of translating 124I-AK104 into a method for screening patients who benefit from immunotherapy and the efficacy, as well as the feasibility, of this method was verified by immuno-PET imaging of humanized mice. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0753-3322 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S0753332224005535; https://doaj.org/toc/0753-3322; https://doaj.org/article/13404cc6508345a7bca0ac26b12a45c3 |
| DOI: | 10.1016/j.biopha.2024.116669 |
| الاتاحة: | https://doi.org/10.1016/j.biopha.2024.116669 https://doaj.org/article/13404cc6508345a7bca0ac26b12a45c3 |
| رقم الانضمام: | edsbas.A9AA4667 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 07533322 |
|---|---|
| DOI: | 10.1016/j.biopha.2024.116669 |