Oyamada T, Okano S
Animal Medical Center, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, 183-0054, Japan.
Laboratory of Small Animal Surgery 2, School of Veterinary Medicine, Kitasato University, Aomori, 034-8628, Japan.
Iran J Vet Res. 2020 Fall;21(4):263-268.
Trastuzumab is an antibody drug used to treat human epidermal growth factor receptor 2 (HER2) overexpressing human metastatic breast cancer. Antibody-dependent cellular cytotoxicity (ADCC) is considered to be the major mechanism of cytotoxicity of the drug. However, its ability to induce an ADCC response in canine peripheral blood mononuclear cells (PBMCs) is not well established.
We aimed to evaluate the ability of trastuzumab in enhancing the cytotoxicity of PBMCs against canine tumor cells.
We used canine tumor cell lines isolated from metastatic mammary gland tumors (CHMm and CIPm) and thyroid adenocarcinoma (CTAC). The binding of trastuzumab to the cells was confirmed using flow cytometry analysis. Peripheral blood mononuclear cells obtained from healthy beagles and lymphokine-activated killer (LAK) cells, generated by interleukin-2 (IL-2) stimulation of PBMCs, were used as effector cells. Standard lactate dehydrogenase (LDH) release assay was used to measure the cytotoxicity of the LAK cells against tumor cell lines in the presence of trastuzumab.
Trastuzumab enhanced the cytotoxicity of PBMCs against CHMm. Moreover, LAK cells killed CHMm synergistically in the presence of trastuzumab. However, the presence of trastuzumab did not produce such a synergistic effect when LAK cells acted against CIPm and CTAC.
We confirmed the ability of trastuzumab to induce an ADCC response in canine PBMCs and determined its synergistic effect with LAK cells. Although the system in the present study did not show the induction of trastuzumab-mediated ADCC response against all canine tumor cell lines, the results of this study indicate the potential antitumor activity of trastuzumab in canines.
曲妥珠单抗是一种用于治疗人表皮生长因子受体2（HER2）过表达的人转移性乳腺癌的抗体药物。抗体依赖性细胞毒性（ADCC）被认为是该药物细胞毒性的主要机制。然而，其在犬外周血单个核细胞（PBMC）中诱导ADCC反应的能力尚未明确。
我们旨在评估曲妥珠单抗增强PBMC对犬肿瘤细胞细胞毒性的能力。
我们使用了从转移性乳腺肿瘤（CHMm和CIPm）和甲状腺腺癌（CTAC）中分离出的犬肿瘤细胞系。通过流式细胞术分析确认曲妥珠单抗与细胞的结合。从健康比格犬获得的外周血单个核细胞以及通过白细胞介素-2（IL-2）刺激PBMC产生的淋巴因子激活的杀伤细胞（LAK细胞）用作效应细胞。使用标准乳酸脱氢酶（LDH）释放试验来测量在曲妥珠单抗存在下LAK细胞对肿瘤细胞系的细胞毒性。
曲妥珠单抗增强了PBMC对CHMm的细胞毒性。此外，在曲妥珠单抗存在下，LAK细胞协同杀伤CHMm。然而，当LAK细胞作用于CIPm和CTAC时，曲妥珠单抗的存在并未产生这种协同效应。
我们证实了曲妥珠单抗在犬PBMC中诱导ADCC反应的能力，并确定了其与LAK细胞的协同效应。尽管本研究中的系统未显示曲妥珠单抗介导的针对所有犬肿瘤细胞系的ADCC反应的诱导，但本研究结果表明曲妥珠单抗在犬中具有潜在的抗肿瘤活性。
