Ahmed Marya, Pan Dorothy W, Davis Mark E
Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
Bioconjug Chem. 2015 May 20;26(5):812-6. doi: 10.1021/acs.bioconjchem.5b00139. Epub 2015 Apr 16.
Antibody-dependent cellular cytotoxicity (ADCC) is a cytolytic mechanism that can elicit in vivo antitumor effects and can play a significant role in the efficacy of antibody treatments for cancer. Here, we prepared cetuximab, panitumumab, and rituximab containing gold nanoparticles and investigated their ability to produce an ADCC effect in vivo. Cetuximab treatment of EGFR-expressing H1975 tumor xenografts showed significant tumor regression due to the ADCC activity of the antibody in vivo, while the control antibody, panitumumab, did not. However, all three antibody containing nanoparticles are not able to suppress tumor growth in the same in vivo mouse model. The antibody containing nanoparticles localized in the tumors and did not suppress the immune function of the animals, so the lack of tumor growth suppression of the cetuximab containing nanoparticle suggests that immobilizing antibodies onto a nanoparticle significantly decreases the ability of the antibody to promote an ADCC response.
抗体依赖性细胞毒性(ADCC)是一种细胞溶解机制,可在体内引发抗肿瘤作用,并在癌症抗体治疗的疗效中发挥重要作用。在此,我们制备了含有金纳米颗粒的西妥昔单抗、帕尼单抗和利妥昔单抗,并研究了它们在体内产生ADCC效应的能力。用西妥昔单抗治疗表达表皮生长因子受体(EGFR)的H1975肿瘤异种移植瘤时,由于抗体在体内的ADCC活性,肿瘤出现了显著消退,而对照抗体帕尼单抗则没有。然而,在同一小鼠体内模型中,所有三种含纳米颗粒的抗体均无法抑制肿瘤生长。含纳米颗粒的抗体定位于肿瘤中,并未抑制动物的免疫功能,因此含纳米颗粒的西妥昔单抗缺乏肿瘤生长抑制作用表明,将抗体固定在纳米颗粒上会显著降低抗体促进ADCC反应的能力。