Maitake Beta-Glucan Enhances the Therapeutic Effect of Trastuzumab via Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity.

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Yuki Masuda, Shizuka Yamashita, Y. Nakayama, Ryohei Shimizu, M. Konishi
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Abstract

Trastuzumab, an anti-HER2 monoclonal antibody, is the mainstay treatment for of HER2-positive breast cancer. However, trastuzumab resistance is often observed during treatment. Therefore, new therapeutic strategies are needed to enhance the clinical benefits of trastuzumab. Maitake β-glucan MD-Fraction, isolated from Grifola frondosa, inhibits tumor growth by enhancing immune responses. In this study, we examined the effect of MD-Fraction on trastuzumab treatment of HER2-positive breast cancer. MD-Fraction did not directly inhibit the survival of HER2-positive breast cancer cells, alone or in the presence of trastuzumab in vitro. In HER2-positive xenograft models, the combination of MD-Fraction and trastuzumab was more effective than trastuzumab alone. Peripheral blood lymphocytes and splenic natural killer cells isolated from BALB/c nu/nu mice treated with MD-Fraction showed enhanced trastuzumab-induced antibody-dependent cellular cytotoxicity (ADCC) ex vivo. MD-Fraction-treated macrophages and neutrophils did not show enhanced trastuzumab cytotoxicity in the presence of heat-inactivated serum, but they showed enhanced cytotoxicity in the presence of native serum. These results suggest that MD-Fraction-treated macrophages and neutrophils enhance trastuzumab-induced complement-dependent cellular cytotoxicity (CDCC). Treatment of HER2-positive breast cancer cells with MD-Fraction in the presence of trastuzumab and native serum increased C3a release and tumor cell lysis in a dose-dependent manner, indicating that MD-Fraction enhanced trastuzumab-induced complement-dependent cytotoxicity (CDC) by activating the complement system. This study demonstrates that the combination of trastuzumab and MD-Fraction exerts a greater antitumor effect than trastuzumab alone by enhancing ADCC, CDCC, and CDC in HER2-positive breast cancer.
麦门冬β-葡聚糖通过抗体依赖性细胞毒性和补体依赖性细胞毒性增强曲妥珠单抗的治疗效果
曲妥珠单抗是一种抗 HER2 单克隆抗体,是治疗 HER2 阳性乳腺癌的主要药物。然而,在治疗过程中经常会观察到曲妥珠单抗的耐药性。因此,需要新的治疗策略来提高曲妥珠单抗的临床疗效。从灰树花中分离出的麦冬β-葡聚糖MD-馏分可通过增强免疫反应抑制肿瘤生长。在这项研究中,我们考察了 MD-Fraction 对曲妥珠单抗治疗 HER2 阳性乳腺癌的效果。在体外,单独或在曲妥珠单抗存在的情况下,MD-Fraction 都不能直接抑制 HER2 阳性乳腺癌细胞的存活。在HER2阳性异种移植模型中,MD-Fraction和曲妥珠单抗的组合比单独使用曲妥珠单抗更有效。经 MD-Fraction 处理的 BALB/c nu/nu 小鼠的外周血淋巴细胞和脾脏自然杀伤细胞显示出更强的曲妥珠单抗诱导的抗体依赖性细胞毒性(ADCC)。经 MD-Fraction 处理的巨噬细胞和中性粒细胞在有热灭活血清存在的情况下未显示出增强的曲妥珠单抗细胞毒性,但在有原生血清存在的情况下显示出增强的细胞毒性。这些结果表明,经 MD-Fraction 处理的巨噬细胞和中性粒细胞可增强曲妥珠单抗诱导的补体依赖性细胞毒性(CDCC)。在曲妥珠单抗和原生血清存在的情况下,用MD-Fraction处理HER2阳性乳腺癌细胞,可增加C3a的释放,并以剂量依赖性的方式溶解肿瘤细胞,这表明MD-Fraction通过激活补体系统增强了曲妥珠单抗诱导的补体依赖性细胞毒性(CDC)。这项研究表明,与单用曲妥珠单抗相比,曲妥珠单抗和MD-Fraction联合使用可增强HER2阳性乳腺癌患者的ADCC、CDCC和CDC,从而发挥更大的抗肿瘤作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
期刊介绍: Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.
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