Department of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, Schillingallee 69, 18057, Rostock, Germany.
Shenzhen University General Hospital & Shenzhen University Clinical Medical Academy, Xueyuan Road 1098, 518055, Shenzhen, China.
Br J Cancer. 2021 Apr;124(8):1411-1420. doi: 10.1038/s41416-021-01272-6. Epub 2021 Feb 9.
Recent evidence proves that intravenous human immunoglobulin G (IgG) can impair cancer cell viability. However, no study evaluated whether IgG application benefits cancer patients receiving chemotherapeutics.
Influence of pharmaceutical-grade human IgG on the viability of a series of patient-derived colon cancer cell lines with and without chemotherapeutic intervention was determined. Cell death was analysed flow cytometrically. In addition, the influence of oxaliplatin and IgG on the ERK1/2-signalling pathway was evaluated by western blots.
We evaluated the effects of pharmaceutical IgG, such as PRIVIGEN IgG and Tonglu IgG, in combination with chemotherapeutics. We did not observe any significant effects of IgG on tumour cell viability directly; however, human IgG significantly impaired the anti-tumoral effects of oxaliplatin. Primary cancer cell lines express IgG receptors and accumulate human IgG intracellularly. Moreover, while oxaliplatin induced the activation of ERK1/2, the pharmaceutical IgG inhibited ERK1/2 activity.
The present study demonstrates that pharmaceutical IgG, such as PRIVIGEN IgG and Tonglu IgG, can impair the anti-carcinoma activity of oxaliplatin. These data strongly suggest that therapeutic IgG as co-medication might have harmful side effects in cancer patients. The clinical significance of these preclinical observations absolutely advises further preclinical, as well as epidemiological and clinical research.
最近的证据证明静脉注射人免疫球蛋白 G（IgG）可以降低癌细胞活力。然而，尚无研究评估 IgG 应用是否有益于接受化疗的癌症患者。
测定了一系列具有和不具有化疗干预的患者来源的结肠癌细胞系中药物级人 IgG 对细胞活力的影响。通过流式细胞术分析细胞死亡。此外，通过 Western blot 评估了奥沙利铂和 IgG 对 ERK1/2 信号通路的影响。
我们评估了药物 IgG（如 PRIVIGEN IgG 和 Tonglu IgG）与化疗联合使用的效果。我们没有观察到 IgG 对肿瘤细胞活力有直接显著影响；然而，人 IgG 显著削弱了奥沙利铂的抗肿瘤作用。原发性癌细胞系表达 IgG 受体并在细胞内积累人 IgG。此外，虽然奥沙利铂诱导了 ERK1/2 的激活，但药物 IgG 抑制了 ERK1/2 的活性。
本研究表明，药物 IgG（如 PRIVIGEN IgG 和 Tonglu IgG）可削弱奥沙利铂的抗癌活性。这些数据强烈表明，治疗性 IgG 作为辅助药物可能会对癌症患者产生有害的副作用。这些临床前观察的临床意义绝对需要进一步的临床前、流行病学和临床研究。
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