Rabbit Anti-Human FCGR2A monoclonal antibody, clone KN21-81

Several studies already explored associations between Fc gamma receptor (FCGR) polymorphisms and immune thrombocytopenia (ITP), but the results of these studies were not consistent. Consequently, we conducted a meta-analysis of relevant studies to better analyse the effects of FCGR polymorphisms on individual susceptibility to ITP. PubMed, Web of Science, Embase and CNKI were searched for eligible studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Totally 17 studies were eligible for analyses (1200 cases and 1723 controls). Significant associations with ITP were observed for FCGR3A F158V polymorphism in dominant (P < 0.0001, OR = 0.47, 95% CI 0.39-0.57), recessive (P < 0.0001, OR = 2.03, 95% CI 1.58-2.61), overdominant (P < 0.0001, OR = 1.42, 95% CI 1.19-1.69) and allele (P < 0.0001, OR = 0.58, 95% CI 0.51-0.65) models in overall analyses. But we did not observe any significant associations with ITP for FCGR2A H131R and FCGR2B I232T polymorphisms in overall analyses. Subgroup analyses by ethnicity yielded similar positive results for FCGR3A F158V polymorphism in both Asians and Caucasians. Furthermore, subgroup analyses by type of disease revealed that FCGR2A H131R polymorphism was significantly associated with childhood-onset ITP, and FCGR3A F158V polymorphism was significantly associated with both childhood-onset and adult-onset ITP. In summary, our findings suggested that FCGR2A H131R polymorphism may serve as a potential genetic biomarker of childhood-onset ITP, while FCGR3A F158V polymorphism may serve as a potential genetic biomarker of both childhood-onset and adult-onset ITP.

Purpose: Fc-gamma receptors (FCGRs) are expressed on immune cells, bind to antibodies, and trigger antibody-induced cell-mediated antitumor responses when tumor-reactive antibodies are present. The affinity of the FCGR/antibody interaction is variable and dependent upon FCGR polymorphisms. Prior studies of patients with cancer treated with immunotherapy indicate that FCGR polymorphisms can influence antitumor response for certain immunotherapies that act via therapeutically administered mAbs or via endogenous tumor-reactive antibodies induced from tumor antigen vaccines. The previously published "SELECT" trial of high-dose aldesleukin (HD-IL2) for metastatic renal cell carcinoma resulted in an objective response rate of 25%. We evaluated the patients in this SELECT trial to determine whether higher-affinity FCGR polymorphisms are associated with outcome. Experimental Design: SNPs in FCGR2A, FCGR3A, and FCGR2C were analyzed, individually and in combination, for associations between genotype and clinical outcome. Results: When higher-affinity genotypes for FCGR2A, FCGR3A, and FCGR2C were considered together, they were associated with significantly increased tumor shrinkage and prolonged survival in response to HD-IL2. Conclusions: Although associations of higher-affinity FCGR genotype with clinical outcome have been demonstrated with mAb therapy and with idiotype vaccines, to our knowledge, this is the first study to show associations of FCGR genotypes with outcome following HD-IL2 treatment. We hypothesize that endogenous antitumor antibodies may engage immune cells through their FCGRs, and HD-IL2 may enhance antibody-induced tumor destruction, or antibody-enhanced tumor antigen presentation, via augmented activation of innate or adaptive immune responses; this FCGR-mediated immune activity would be augmented through immunologically favorable FCGRs. (C) 2016 AACR.