抗 CD44 单克隆抗体在食管癌小鼠异种移植模型中的抗肿瘤活性。

IF 3.8 3区 医学 Q2 ONCOLOGY Oncology reports Pub Date : 2024-11-01 Epub Date: 2024-09-02 DOI:10.3892/or.2024.8806
Kenichiro Ishikawa, Hiroyuki Suzuki, Tomokazu Ohishi, Takuro Nakamura, Miyuki Yanaka, Guanjie Li, Tomohiro Tanaka, Akira Ohkoshi, Manabu Kawada, Mika K Kaneko, Yukio Katori, Yukinari Kato
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引用次数: 0

摘要

CD44 是一种 I 型跨膜糖蛋白,与各种实体瘤的不良预后有关。由于 CD44 通过调节细胞粘附、存活、增殖和干性在肿瘤发生发展过程中起着关键作用,因此一直被认为是肿瘤治疗的靶点。抗 CD44 单克隆抗体(mAbs)已被开发并应用于抗体-药物共轭物和嵌合抗原受体-T 细胞疗法。抗泛 CD44 mAbs(C44Mab-5 和 C44Mab-46)既能识别 CD44 标准异构体(CD44s),也能识别变异异构体。本研究生成了抗泛CD44 mAbs的小鼠IgG2a版本(5-mG2a和C44Mab-46-mG2a),以评估其对CD44阳性细胞的抗肿瘤活性。在流式细胞术中,5-mG2a和C44Mab-46-mG2a都能识别CD44s过度表达的CHO-K1(CHO/CD44s)细胞和食管肿瘤细胞系(KYSE770)。此外,5-mG2a 和 C44Mab-46-mG2a 都能在 CHO/CD44s 细胞存在的情况下激活效应细胞,并对 CHO/CD44s 和 KYSE770 细胞表现出补体依赖性细胞毒性。此外,与对照小鼠 IgG2a 相比,5-mG2a 和 C44Mab-46-mG2a 能显著抑制 CHO/CD44s 和 KYSE770 异种移植肿瘤的发展。这些结果表明,5-mG2a和C44Mab-46-mG2a可对CD44阳性癌症发挥抗肿瘤活性,是一种很有前景的肿瘤治疗方案。
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Antitumor activities of anti‑CD44 monoclonal antibodies in mouse xenograft models of esophageal cancer.

CD44 is a type I transmembrane glycoprotein associated with poor prognosis in various solid tumors. Since CD44 plays a critical role in tumor development by regulating cell adhesion, survival, proliferation and stemness, it has been considered a target for tumor therapy. Anti‑CD44 monoclonal antibodies (mAbs) have been developed and applied to antibody‑drug conjugates and chimeric antigen receptor‑T cell therapy. Anti-pan‑CD44 mAbs, C44Mab‑5 and C44Mab‑46, which recognize both CD44 standard (CD44s) and variant isoforms were previously developed. The present study generated a mouse IgG2a version of the anti‑pan‑CD44 mAbs (5‑mG2a and C44Mab‑46‑mG2a) to evaluate the antitumor activities against CD44‑positive cells. Both 5‑mG2a and C44Mab‑46‑mG2a recognized CD44s‑overexpressed CHO‑K1 (CHO/CD44s) cells and esophageal tumor cell line (KYSE770) in flow cytometry. Furthermore, both 5‑mG2a and C44Mab‑46‑mG2a could activate effector cells in the presence of CHO/CD44s cells and exhibited complement-dependent cytotoxicity against both CHO/CD44s and KYSE770 cells. Furthermore, the administration of 5‑mG2a and C44Mab‑46‑mG2a significantly suppressed CHO/CD44s and KYSE770 xenograft tumor development compared with the control mouse IgG2a. These results indicate that 5‑mG2a and C44Mab‑46‑mG2a could exert antitumor activities against CD44‑positive cancers and be a promising therapeutic regimen for tumors.

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来源期刊
Oncology reports
Oncology reports 医学-肿瘤学
CiteScore
8.50
自引率
2.40%
发文量
187
审稿时长
3 months
期刊介绍: Oncology Reports is a monthly, peer-reviewed journal devoted to the publication of high quality original studies and reviews concerning a broad and comprehensive view of fundamental and applied research in oncology, focusing on carcinogenesis, metastasis and epidemiology.
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