Lisboa, Portugal.
Oeiras, Portugal.
Aliment Pharmacol Ther. 2018 Sep;48(5):507-522. doi: 10.1111/apt.14808. Epub 2018 Jun 5.
To test the cross-immunogenicity of anti-CT-P13 IBD patients' sera to CT-P13/infliximab originator and the comparative antigenicity evoked by CT-P13/infliximab originator sera.
Sera of patients with IBD with measurable anti-CT-P13 antibodies were tested for their cross-reactivity to 5 batches of infliximab originator and CT-P13. Anti-drug antibody positive sera from treated patients were used to compare antigenic epitopes.
All 42 anti-CT-P13 and 37 anti-infliximab originator IBD sera were cross-reactive with infliximab originator and CT-P13 respectively. Concentration of anti-drug antibodies against infliximab originator or CT-P13 were strongly correlated both for IgG1 and IgG4 (P < 0.001). Anti-CT-P13 sera of patients with IBD (n = 32) exerted similar functional inhibition on CT-P13 or infliximab originator TNF binding capacity and showed reduced binding to CT-P13 in the presence of five different batches of CT-P13 and infliximab originator. Anti-CT-P13 and anti-infliximab originator IBD sera selectively enriched phage-peptides from the VH (CDR1 and CDR3) and VL domains (CDR2 and CDR3) of infliximab. Sera reactivity detected major infliximab epitopes in these regions of infliximab in 60%-79% of patients, and no significant differences were identified between CT-P13 and infliximab originator immunogenic sera. Minor epitopes were localised in framework regions of infliximab with reduced antibody reactivity shown, in 30%-50% of patients. Monoclonal antibodies derived from naïve individuals and ADA-positive IBD patients treated with CT-P13 provided comparable epitope specificity to five different batches of CT-P13 and infliximab originator.
These results strongly support a similar antigenic profile for infliximab originator and CT-P13, and point toward a safe switching between the two drugs in anti-drug antibody negative patients.
检测抗 CT-P13 的 IBD 患者血清对 CT-P13/英夫利昔单抗原研药物的交叉免疫原性，以及 CT-P13/英夫利昔单抗原研药物血清引起的比较抗原性。
检测抗 CT-P13 抗体可测的 IBD 患者血清对 5 批英夫利昔单抗原研药物和 CT-P13 的交叉反应性。用治疗患者的抗药物抗体阳性血清比较抗原表位。
所有 42 份抗 CT-P13 和 37 份抗英夫利昔单抗原研药物的 IBD 血清分别与英夫利昔单抗原研药物和 CT-P13 发生交叉反应。抗英夫利昔单抗原研药物或 CT-P13 抗体的浓度与 IgG1 和 IgG4 均呈强相关（P<0.001）。32 例 IBD 患者的抗 CT-P13 血清对 CT-P13 或英夫利昔单抗原研药物 TNF 结合能力具有相似的功能抑制作用，并在存在 5 种不同批次的 CT-P13 和英夫利昔单抗原研药物时，降低与 CT-P13 的结合。抗 CT-P13 和抗英夫利昔单抗原研药物的 IBD 血清选择性地从英夫利昔单抗的 VH（CDR1 和 CDR3）和 VL 结构域（CDR2 和 CDR3）中富集噬菌体肽。血清反应性在 60%-79%的患者中检测到英夫利昔单抗这些区域的主要表位，并且在 CT-P13 和英夫利昔单抗原研药物免疫原性血清之间没有发现显著差异。次要表位定位于英夫利昔单抗的框架区域，抗体反应性降低，在 30%-50%的患者中。从无经验个体和接受 CT-P13 治疗的 ADA 阳性 IBD 患者中获得的单克隆抗体提供了与 5 种不同批次的 CT-P13 和英夫利昔单抗原研药物相似的表位特异性。
这些结果强烈支持英夫利昔单抗原研药物和 CT-P13 具有相似的抗原谱，并指向在抗药物抗体阴性患者中两种药物之间的安全转换。
