Antibodies against growth factor receptors can inhibit the proliferation of transformed cells via a cis-interaction with inhibitory FcR

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• 作者：Odile Malbec^a ; ^b ; Marc Daë ; ron^a ; ^b ; ^{daeron@pasteur.fr}
• 关键词：Antibodies ; Fc receptors ; Immunoregulation ; Cell proliferation ; Cancer
• 刊名：Immunology Letters
• 出版年：2012
• 期刊代码：115_01652478
• 类别：med
• 出版时间：30 March, 2012
• 卷：143
• 期：1
• 页码：28-33
• 文件大小：833 K

摘要

When dimerized by Stem Cell Factor (SCF), the Receptor Tyrosine Kinase Kit triggers the proliferation of hematopoietic progenitors, including pro-B cells, and of some differentiated cells, including mast cells. We found previously that anti-Kit antibodies can mimic SCF and that anti-Kit-induced mast cell proliferation can be inhibited by the low-affinity IgG receptors Fc纬RIIB, when the two receptors are co-aggregated by IgG immune complexes. We show here that the same immune complexes inhibited anti-Kit-induced proliferation of Ba/F3 pro-B cells expressing wt Kit and Fc纬RIIB and that inhibition required the intracytoplasmic domain of Fc纬RIIB. Constitutively active Kit mutants are oncogenic. We show that Kit-dependent, ligand-independent proliferation of Ba/F3 cells expressing a constitutively dimerized Kit mutant was also inhibited by IgG immune complexes via Fc纬RIIB. Fc纬RIIB-dependent negative regulation therefore also affects Kit-dependent proliferation of transformed cells. Interestingly, the co-aggregation of Kit with Fc纬RIIB by immune complexes containing SCF also inhibited both growth factor-dependent and growth factor-independent proliferation of Ba/F3 cells expressing wt or mutated Kit, respectively. These results provide the basis for novel immunotherapeutical approaches of Fc纬RIIB-expressing tumors.