A phase I clinical trial demonstrates that nfP2X7-targeted antibodies provide a novel, safe and tolerable topical therapy for basal cell carcinoma
A phase I clinical trial demonstrates that nfP2X7-targeted antibodies provide a novel, safe and tolerable topical therapy for basal cell carcinoma
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DOI：
10.1111/bjd.15364
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发表时间：
2017-07-01
影响因子：
10.3
通讯作者：
King, J.
中科院分区：
文献类型：
--
作者：
Gilbert, S. M.;Baird, A. Gidley;King, J.
P2X(7)是一种atp门控的钙通道，其表达可增加癌细胞的增殖和侵袭性。P2X(7)的一种变体（称为nfP2X(7)），其中一个通常隐藏的表位（E200）暴露于抗体结合，在多种不同的癌症中被观察到。目的研究一种新型抗体软膏治疗基底细胞癌（BCC）的安全性、耐受性和药代动力学，并评价其指示性疗效。方法在三家皮肤科诊所进行了一项开放标签的I期临床试验，以评估含有10%羊多克隆抗nfp2x(7)抗体（BIL010t）的软膏对原发性BCC病变的安全性和耐受性，每日两次，持续28天。21例原发性BCC病变面积至少0.5 cm(2)，直径小于2.0 cm的患者被纳入研究。主要终点是安全性、耐受性和药代动力学。测定治疗后病变大小的变化，并对治疗前和治疗结束（EOT）活检进行组织学检查。结果依从性高，治疗耐受性好。最常见的不良事件是治疗部位红斑、瘙痒、干燥和疼痛。没有证据表明绵羊抗体全身渗透。在治疗前和治疗后28天测量病变，65%的患者显示病变面积减少，20%没有变化，15%增加。治疗后切除病灶部位的组织病理学显示病情稳定8例，部分缓解9例，完全缓解3例。结论抗nfP2X(7) （BIL010t）抗体为BCC提供了一种新型、安全且耐受性良好的治疗方法。
Background Expression of P2X(7), an ATP-gated calcium channel, increases cancer cell proliferation and invasiveness. A variant of P2X(7) (termed nfP2X(7)), in which a normally hidden epitope (E200) is exposed for antibody binding, is observed in a variety of different cancers.Objectives To investigate the safety, tolerability and pharmacokinetics and assess indicative efficacy of a novel antibody ointment as a therapeutic for basal cell carcinoma (BCC).Methods An open-label, phase I clinical trial was undertaken at three dermatology clinics to evaluate the safety and tolerability of topical administration of an ointment containing 10% sheep polyclonal anti-nfP2X(7) antibodies (BIL010t) to primary BCC lesions twice daily for 28 days. Twenty-one patients with primary BCC lesions at least 0.5 cm(2) in area and less than 2.0 cm in diameter were enrolled. The primary end points were safety, tolerability and pharmacokinetics. Change in lesion size after treatment was determined and histology was performed on pretreatment and end-of-treatment (EOT) biopsies.Results Compliance was very high, with treatment being well tolerated. The most common adverse events were treatment site erythema, pruritus, dryness and pain. There was no evidence of systemic penetration of the sheep antibody. Lesions were measured prior to and after 28 days of treatment, with 65% of patients showing a reduction in lesion area, 20% showing no change and 15% showing an increase. Histopathology of post-treatment excision of lesion sites showed eight patients with stable disease, nine with partial response and three with complete response.Conclusions Antibodies against nfP2X(7) (BIL010t) provide a novel, safe and well-tolerated treatment for BCC.