Medical Sciences (Clinical Immunology and Biostatistics), Amgen, Thousand Oaks, CA, USA.
Clin Immunol. 2010 Oct;137(1):5-14. doi: 10.1016/j.clim.2010.06.018. Epub 2010 Aug 13.
An immune response to a biotherapeutic can be induced when the therapeutic is processed and presented by antigen presenting cell to T helper cells. This study evaluates the performance of an in vitro assay that can elicit antigen specific effector T cell responses. Two biotherapeutics with known clinical immunogenicity [FPX1 and FPX2] were assessed for their ability to induce antigen-specific IFN-γ secreting T cells in peripheral blood mononuclear cells (PBMC). The 24 amino acid peptide component of FPX1 elicited an antigen-specific response in 16/34 (47%) individual naïve healthy donors. This in vitro effect was consistent with high rate of immunogenicity which was observed when this drug was administered in clinical trials. FPX2 did not induce antigen-specific T cells in vitro, which correlates with the low rate of development of anti-drug antibody responses to this molecule in the clinic. The assay has the potential to predict immunogenicity and help in the selection of biotherapeutics at the early development stage of a clinical candidate.
当治疗性药物被抗原呈递细胞加工并呈递给辅助性 T 细胞时，可能会引发针对生物治疗药物的免疫反应。本研究评估了一种能够引发抗原特异性效应 T 细胞反应的体外检测方法的性能。两种具有已知临床免疫原性的生物治疗药物[FPX1 和 FPX2]被评估其在体外诱导外周血单个核细胞（PBMC）中抗原特异性 IFN-γ分泌 T 细胞的能力。FPX1 的 24 个氨基酸肽成分在 34 名个体健康供体中的 16 名（47%）中引发了抗原特异性反应。这种体外效应与该药物在临床试验中观察到的高免疫原性一致。FPX2 并未在体外诱导抗原特异性 T 细胞，这与该分子在临床中产生抗药物抗体反应的低发生率相关。该检测方法具有预测免疫原性的潜力，并有助于在临床候选药物的早期开发阶段选择生物治疗药物。
