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重组肿瘤源性独特型疫苗用于惰性B细胞非霍奇金淋巴瘤:聚焦于FavId

Recombinant, tumour-derived idiotype vaccination for indolent B cell non-Hodgkin's lymphomas: a focus on FavId.

作者信息

Hurvitz Sara A, Timmerman John M

机构信息

Division of Hematology-Oncology, UCLA Center for Health Sciences, Room 42-121, Los Angeles, California 90095-1678, USA.

出版信息

Expert Opin Biol Ther. 2005 Jun;5(6):841-52. doi: 10.1517/14712598.5.6.841.

Abstract

FavId (Favrille, Inc., San Diego, CA, USA) is a personalized therapeutic vaccine product for B cell non-Hodgkin's lymphoma, custom-manufactured from individual patient's tumour cells. This investigational agent consists of recombinant tumour-specific immunoglobulin (idiotype [Id]) chemically conjugated to the highly immunogenic carrier protein keyhole limpet haemocyanin (Id-KLH). The vaccine product is administered by subcutaneous co-injection with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF) with the goal of stimulating tumour-specific T cell and humoral immunity. Therapeutic Id vaccines have shown promising results in early phase clinical trials in follicular lymphoma, and several Phase III trials are ongoing. FavId's advantages over other Id vaccine formulations include its rapid and efficient manufacturing technology utilising recombinant baculovirus, with a production time of only 8-12 weeks. In Phase II studies, FavId Id-KLH plus GM-CSF vaccines have been found to be safe, immunogenic and clinically active in follicular lymphoma. At present, FavId is being tested in a randomised, placebo-controlled Phase III trial in follicular lymphoma, aimed at improving the time to disease progression when administered following cytoreduction with rituximab. If found to be efficacious in this pivotal trial, FavId would represent a tumour-selective immunotherapy for lymphoma with little toxicity and a novel mechanism of action.

摘要

FavId(美国加利福尼亚州圣地亚哥市的法夫里尔公司)是一种用于B细胞非霍奇金淋巴瘤的个性化治疗性疫苗产品,由个体患者的肿瘤细胞定制生产。这种研究性药物由与高度免疫原性载体蛋白钥孔戚血蓝蛋白化学偶联的重组肿瘤特异性免疫球蛋白(独特型[Id])组成(Id-KLH)。该疫苗产品通过与细胞因子佐剂粒细胞巨噬细胞集落刺激因子(GM-CSF)皮下联合注射给药,目的是刺激肿瘤特异性T细胞和体液免疫。治疗性Id疫苗在滤泡性淋巴瘤的早期临床试验中已显示出有前景的结果,并且多项III期试验正在进行。FavId相对于其他Id疫苗制剂的优势包括其利用重组杆状病毒的快速高效生产技术,生产时间仅为8-12周。在II期研究中,已发现FavId Id-KLH加GM-CSF疫苗在滤泡性淋巴瘤中是安全的、具有免疫原性且具有临床活性。目前,FavId正在滤泡性淋巴瘤的一项随机、安慰剂对照III期试验中进行测试,旨在改善在用利妥昔单抗进行细胞减灭后给药时的疾病进展时间。如果在这项关键试验中被证明有效,FavId将代表一种毒性小且作用机制新颖的淋巴瘤肿瘤选择性免疫疗法。

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