Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin lymphoma
Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin lymphoma
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DOI：
10.1182/blood-2003-09-3284
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发表时间：
2004-07-01
期刊：
影响因子：
20.3
通讯作者：
Meredith, RF
中科院分区：
文献类型：
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作者：
Forero, A;Weiden, PL;Meredith, RF
前靶向放射免疫治疗(PRIT)有可能增加向肿瘤输送的放射性核素的剂量，同时限制对正常组织的辐射。这项第一阶段试验的目的是评估使用新型四聚体单链抗CD20-链霉亲和素融合蛋白(B9E9FP)作为靶向部分治疗B细胞非霍奇金淋巴瘤(NHL)的这种多步骤方法的安全性，并表征其药代动力学和免疫原性。所有患者接受B9E9FP(160 mg/m(2)或320 mg/m(2))，48或72小时后，给予合成清洗剂(SCA)(45 mg/m(2))以清除循环中游离的B9E9FP。(90)24小时后注射Y(Y-90；15mCL/m(2))/In-111(5mCL)-DOTA-生物素。有15名患者参加了这项研究。B9E9FP的平均血浆半衰期(T-1/(2))为25+/-6小时，给药后6小时内血药浓度下降95%以上。Y-90/In-111-DOTA-生物素注射可使肿瘤快速定位和尿液排泄。肿瘤平均剂量与全身照射剂量之比为49：1。12例患者未见明显的血液学毒性反应。有2例患者出现与进展性疾病有关的血液毒性。2例完全缓解(90天和325天)，1例部分缓解(297天)。B9E9FP作为PRIT的靶向成分表现良好，具有令人鼓舞的剂量学、安全性和有效性。Y-90-DOTA-生物素这种形式的剂量递增试验是必要的。
Pretargeted radioimmunotherapy (PRIT) has the potential to increase the dose of radionuclide delivered to tumors while limiting radiation to normal tissues. The purpose of this phase 1 trial is to assess safety of this multistep approach using a novel tetrameric single-chain anti-CD20-streptavidin fusion protein (B9E9FP) as the targeting moiety in patients with B-cell non-Hodgkin lymphoma (NHL), and to characterize its pharmacokinetics and immunogenicity. All patients received B9E9FP (160 mg/m(2) or 320 mg/m(2)); either 48 or 72 hours later, a synthetic clearing agent (sCA) was administered (45 mg/m(2)) to remove circulating unbound B9E9FP. (90)Yttrium (Y-90; 15 mCl/m(2))/In-111 (5 mCl)-DOTA-biotin was injected 24 hours later. There were 15 patients enrolled in the study. B9E9FP had a mean plasma half-life (T-1/(2)) of 25 +/- 6 hours with a reduction in plasma level of more than 95% within 6 hours of sCA administration. Y-90/In-111-DOTA-biotin infusion resulted in rapid tumor localization and urinary excretion. The ratio of average tumor to whole-body radiation dose was 49:1. No significant hematologic toxicities were noted in 12 patients. There were 2 patients who had hematologic toxicity related to progressive disease. There were 2 complete remissions (90 and 325 days) and one partial response (297 days). B9E9FP performs well as the targeting component of PRIT with encouraging dosimetry, safety, and efficacy. A dose escalation trial of Y-90-DOTA-biotin in this format is warranted.