Otten Marielle A, Rudolph Esther, Dechant Michael, Tuk Cornelis W, Reijmers Rogier M, Beelen Robert H J, van de Winkel Jan G J, van Egmond Marjolein
Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, The Netherlands.
J Immunol. 2005 May 1;174(9):5472-80. doi: 10.4049/jimmunol.174.9.5472.
Antitumor Abs are promising therapeutics for cancer. Currently, most Ab-based therapies focus on IgG Ab, which interact with IgG FcR (FcgammaR) on effector cells. In this study, we examined human and mouse neutrophil-mediated tumor cell lysis via targeting the IgA FcR, FcalphaRI (CD89), in more detail. FcalphaRI was the most effective FcR in triggering tumor cell killing, and initiated enhanced migration of neutrophils into tumor colonies. Importantly, immature neutrophils that are mobilized from the bone marrow upon G-CSF treatment efficiently triggered tumor cell lysis via FcalphaRI, but proved incapable of initiating tumor cell killing via FcgammaR. This may provide a rationale for the disappointing results observed in some earlier clinical trials in which patients were treated with G-CSF and antitumor Ab-targeting FcgammaR.
抗肿瘤抗体是很有前景的癌症治疗药物。目前，大多数基于抗体的疗法聚焦于IgG抗体，其与效应细胞上的IgG FcR（FcγR）相互作用。在本研究中，我们更详细地研究了通过靶向IgA FcR即FcalphaRI（CD89）介导的人和小鼠中性粒细胞介导的肿瘤细胞裂解。FcalphaRI是触发肿瘤细胞杀伤最有效的FcR，并引发中性粒细胞向肿瘤集落的迁移增强。重要的是，经G-CSF治疗后从骨髓动员的未成熟中性粒细胞通过FcalphaRI有效触发肿瘤细胞裂解，但经FcγR却无法引发肿瘤细胞杀伤。这可能为一些早期临床试验中观察到的令人失望的结果提供一个解释，在这些试验中，患者接受了G-CSF和靶向FcγR的抗肿瘤抗体治疗。
