Ex Vivo Comparative Immunogenicity Assessment (EVCIA) to Determine Relative Immunogenicity in Chronic Plaque Psoriasis in Participants Receiving Humira® or Undergoing Repeated Switches Between Humira® and AVT02

IF 4.1 Q2 IMMUNOLOGY Immunotherapy advances Pub Date : 2023-12-21 DOI:10.1093/immadv/ltad029
Kathleen Richter, H. Haliduola, Jana Schockaert, Aurélie Mazy, N. Reznichenko, Eric Guenzi, Fausto Berti
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Abstract

Immunogenicity against biologic medicines is ubiquitous, and it is traditionally measured by the final humoral response. However, the onset of a sustained immunogenic response begins at the cellular level with activation of T cells and maturation of naïve B cells into plasma cells. Ex vivo comparative immunogenicity assessment (EVCIA) of cellular immunogenicity in participants with moderate-to-severe chronic plaque psoriasis in the AVT02-GL-302 study, who received either reference product (RP) alone (non-switching arm) or switched between RP and AVT02 (switching arm) after 1: 1 randomization at week 12. Peripheral blood mononuclear cells (PBMCs) were collected and cryopreserved from 28 participants at: baseline (before treatment) (week 1); pre-randomization (week 12); and week 16 and week 28 in both switching and non-switching arms. PBMCs were thawed and re-exposed to either medium alone (negative control), RP, AVT02, keyhole limpet hemocyanin (KLH) (positive control), RP+KLH, or AVT02+KLH. Samples from 10 participants (predetermined average cell viability of 75% across all timepoints) from each arm were analyzed for cytokine release after 24 hours and for Th-cell proliferation, 6 days post-seeding. Until week 28, cytokine release and Th-cell proliferation was similar at all time points in both switching and non-switching arms. Overall cellular immune response was elevated post-KLH re-exposure at all timepoints. The comparable ex vivo cellular immunogenicity between switching and non-switching arms complements the confirmation of interchangeability in the main study. Given the sensitivity of novel EVCIA, detecting cellular immunogenicity could be a potential outcome in predicting the immunogenicity of biologic medicines.
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体内外比较免疫原性评估 (EVCIA),以确定接受 Humira® 治疗或在 Humira® 和 AVT02 之间反复转换的慢性斑块型银屑病患者的相对免疫原性
生物制药的免疫原性无处不在,传统上以最终的体液反应来衡量。然而,持续的免疫原性反应始于细胞水平,即 T 细胞的活化和幼稚 B 细胞成熟为浆细胞。AVT02-GL-302研究的参与者患有中度至重度慢性斑块状银屑病,他们在第12周时经过1:1随机分配后单独接受参比产品(RP)(非转换组)或在RP和AVT02之间进行转换(转换组),对细胞免疫原性进行了体内外比较免疫原性评估(EVCIA)。在基线(治疗前)(第 1 周)、随机化前(第 12 周)、第 16 周和第 28 周(切换组和非切换组)收集并冷冻保存了 28 名参与者的外周血单核细胞(PBMC)。将白细胞介质解冻并重新暴露于单独的培养基(阴性对照)、RP、AVT02、匙孔帽形血蓝蛋白(KLH)(阳性对照)、RP+KLH 或 AVT02+KLH。对每组 10 名参与者(预先确定所有时间点的平均细胞存活率为 75%)的样本进行分析,以检测细胞因子在 24 小时后的释放情况以及播种后 6 天 Th 细胞的增殖情况。在第 28 周之前,切换组和非切换组在所有时间点的细胞因子释放和 Th 细胞增殖情况相似。KLH再次暴露后,所有时间点的整体细胞免疫反应都有所升高。换药组和非换药组的体内外细胞免疫原性相当,这是对主要研究中互换性确认的补充。鉴于新型 EVCIA 的灵敏度,检测细胞免疫原性可能成为预测生物药免疫原性的一个潜在结果。
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