Zolbetuximab是一种特异性靶向claudin-18 isoform 2（CLDN18.2）的嵌合单克隆抗体。
Cas No.:1496553-00-4
Sample solution is provided at 25 µL, 10mM.
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Zolbetuximab is a chimeric monoclonal antibody that specifically targets claudin-18 isoform 2 (CLDN18.2) [1]. Zolbetuximab binds to CLDN18.2 on the tumor cell surface and stimulates cellular and soluble immune effectors that activate antibody-dependent cytotoxicity and complement-dependent cytotoxicity[2]. Zolbetuximab is widely used in preclinical models to inhibit the progression of gastric cancer, and has been employed in the development of new combination therapies[3].
In vitro, Zolbetuximab was incubated with peripheral blood mononuclear cells (PBMCs) from healthy donors for 24 hours, which could significantly lyse NUGC-4 cells with high expression of CLDN18.2, with an EC50 value of 250.4±128.8ng/ml[4].
In vivo, Zolbetuximab treatment via intraperitoneal injection three times a week for five weeks inhibited the tumor volume in SNU-620 cell-xenograft mouse model, without affecting body weight[5]. Intraperitoneal injection of 10mg/kg dose of Zolbetuximab (twice a week; for a total of 13 times) significantly inhibited the growth of SNU-601 tumors in mice[6]. Zolbetuximab treatment (200μg) was continued semi-weekly with alternating i.p. and i.v. injections for 35 days, which suppressed the tumor growth of BxPC-3-CLDN18.2 xenografts in mice[7].
References:
[1] Yamamoto K, Nakayama I, Sakamoto N, et al. Temporal dynamics of CLDN18. 2 expression following zolbetuximab treatment in advanced gastric cancer[J]. ESMO Gastrointestinal Oncology, 2025, 9: 100206.
[2] Kubota Y, Shitara K. Zolbetuximab for Claudin18. 2-positive gastric or gastroesophageal junction cancer[J]. Therapeutic Advances in Medical Oncology, 2024, 16: 17588359231217967.
[3] Zeng Y, Lockhart A C, Jin R U. The preclinical discovery and development of zolbetuximab for the treatment of gastric cancer[J]. Expert opinion on drug discovery, 2024, 19(8): 873-886.
[4] Nishibata T, Weng J, Omori K, et al. Effect of anti-claudin 18.2 monoclonal antibody zolbetuximab alone or combined with chemotherapy or programmed cell death-1 blockade in syngeneic and xenograft gastric cancer models[J]. Journal of Pharmacological Sciences, 2024, 155(3): 84-93.
[5] Zhong W, Lu Y, Ma Z, et al. Development of a humanized VHH based recombinant antibody targeting claudin 18.2 positive cancers[J]. Frontiers in Immunology, 2022, 13: 885424.
[6] Wang R, Wang X, Lian K, et al. Comparison of ADCC-mediated efficacy of zolbetuximab in hCD16A-CB17SCID humanized mice and CB17SCID WT mice bearing the SNU-601 tumor model[J]. Cancer Research, 2025, 85(8_Supplement_1): 7335-7335.
[7] Türeci Ӧ, Mitnacht-Kraus R, Wöll S, et al. Characterization of zolbetuximab in pancreatic cancer models[J]. Oncoimmunology, 2019, 8(1): e1523096.
Zolbetuximab是一种特异性靶向claudin-18 isoform 2（CLDN18.2）的嵌合单克隆抗体[1]。Zolbetuximab与肿瘤细胞表面的CLDN18.2结合，刺激可溶性和细胞性免疫效应因子，激活抗体依赖性细胞毒性和补体依赖性细胞毒性[2]。Zolbetuximab广泛用于临床前模型以抑制胃癌进展，并已被应用于新型联合疗法的开发[3]。
在体外，将Zolbetuximab与健康供体的外周血单核细胞（PBMCs）共孵育24小时，能显著裂解高表达CLDN18.2的NUGC-4细胞，EC50值为250.4±128.8ng/ml[4]。
在体内，每周三次腹腔注射Zolbetuximab，持续五周，抑制了SNU-620细胞异种移植小鼠模型中的肿瘤体积，且未影响体重[5]。腹腔注射10mg/kg剂量的Zolbetuximab（每周两次；共13次）显著抑制了小鼠体内SNU-601肿瘤的生长[6]。持续半周交替腹腔和静脉注射Zolbetuximab（200μg）35天，抑制了小鼠体内BxPC-3-CLDN18.2异种移植瘤的生长[7]。
| Cell experiment [1]: | |
Cell lines | NUGC-4 cells expressing high levels of CLDN18.2-luciferase |
Preparation Method | NUGC-4 cells were seeded in white 96-well plates containing DMEM medium supplemented with 20mM HEPES. Serially diluted Zolbetuximab (0.1, 1, 10, 100, 1000, and 10000ng/ml) or isotype control antibody and PBMCs were added and incubated at 37°C 5% CO2 for 24h. After the overnight incubation, 8% Triton X-100/PBS solution was added to the maximum lysis control wells and PBS to the other wells. Finally, freshly prepared luciferin stock solution (160mM HEPES and 3.84mg/ml D-Luciferin in PBS) was added to each well, and plates were incubated for 90min at room temperature in the dark and bioluminescence was measured. |
Reaction Conditions | 0.1, 1, 10, 100, 1000, and 10000ng/ml; 24h |
Applications | Zolbetuximab treatment induced cell death in NUGC-4 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Female CB17 SCID mice |
Preparation Method | Female CB17 SCID mice were housed in a temperature-controlled (23±2°C) room maintained on a 12/12h light/dark cycle. All mice were adaptively fed for one week. The six-week-old mice were subcutaneously injected with 1×107 SNU-620 cells. Mice were divided into 3 groups of 8 mice each. The control group (group I) received saline and group II received 5.7mg/kg Zolbetuximab. Group III was administered 0.3mg/kg hu7v3-Fc. Test antibodies were given by intraperitoneal injection three times per week (TIW) for five weeks. |
Dosage form | 5.7mg/kg; three times a week for 5 weeks; i.p. |
Applications | Zolbetuximab treatment inhibited the tumor growth in SNU-620 cell-xenograft mouse model. |
References: | |
| Cas No. | 1496553-00-4 | SDF | Download SDF |
| 别名 | 佐妥昔单抗,IMAB362 | ||
| 分子式 | 分子量 | ||
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