Combined vaccination with idiotype-pulsed allogeneic dendritic cells and soluble protein idiotype for multiple myeloma patients relapsing after reduced-intensity conditioning allogeneic stem cell transplantation
Combined vaccination with idiotype-pulsed allogeneic dendritic cells and soluble protein idiotype for multiple myeloma patients relapsing after reduced-intensity conditioning allogeneic stem cell transplantation
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DOI：
10.1080/10428190500272473
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发表时间：
2006-01-01
影响因子：
2.6
通讯作者：
Orfao, A
中科院分区：
文献类型：
--
作者：
Bendandi, M;Rodríguez-Calvillo, M;Orfao, A
背景和目的：将独特型脉冲的同种异体树突状细胞（alloDC）和与 KLH 缀合的可溶性蛋白 Id（Id-KLH）结合起来用于多发性骨髓瘤（MM）的疫苗策略。设计和方法：四名 MM 患者在降低强度调节（RIC）同种异体干细胞移植（alloSCT）后经历疾病复发/进展且无法通过供体淋巴细胞输注或化疗挽救治疗后接受联合疫苗(CHT)。结果：疫苗接种耐受性良好，并在所有 4 名患者中诱导了抗 KLH 抗体反应以及大量细胞增殖。相比之下，没有病例显示出针对肿瘤特异性 Id 或不相关同种型对照免疫球蛋白 (Ig) 的类似效果。反过来，疫苗接种与调节与炎症和 T 细胞激活相关的生物反应以及效应 Th1 细胞因子的分泌有关。特别是，在第四次疫苗接种之前经常观察到TNFα、IL-6和IFNγ以及IL-2和IL-10的自发离体分泌显着增加。此外，在第三次和第四次疫苗接种之前，用Id-KLH和Id-KLH加alloDC（而不是单独的alloDC）体外刺激与TNF-α（+）T细胞数量增加以及IFNγ和IL-2分泌增加相关。从临床角度来看，2名患者出现短暂反应，1名患者在停止接种后病情稳定，而其中3名患者最终出现进展。 解读和结论：结果首次表明，RIC alloSCT后使用Id脉冲alloDC是安全可行的。然而，为了可能实现临床效益，需要进行关键的策略改进。
Background and objective: To combine the use of idiotype-pulsed allogeneic dendritic cells (alloDC) and soluble protein Id conjugated with KLH (Id-KLH) in a vaccine strategy for multiple myeloma (MM).Design and methods: Four MM patients received the combined vaccine after having experienced disease relapse/progression following reduced intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) and failure to rescue therapy with donor lymphocyte infusion or chemotherapy (CHT).Results: Vaccination was well tolerated and induced an anti-KLH antibody response in all 4 patients as well as substantial cell proliferation. In contrast, no case showed similar effects against either tumor-specific Id or irrelevant isotype control immunoglobulins (Ig). In turn, vaccination was associated with modulation of biological responses linked to both inflammatory and T-cell activation, with secretion of effector Th1 cytokines. In particular, an important increase in the spontaneous ex vivo secretion of TNF alpha, IL-6 and IFN gamma as well as IL-2 and IL-10 was frequently observed prior to the fourth vaccination. Moreover, in vitro stimulation with Id-KLH and Id-KLH plus alloDC, but not with alloDC alone was associated with an enhanced number of TNF-alpha(+) T-cells and an increased secretion of IFN gamma and IL-2 before the third and fourth vaccination. From a clinical standpoint, 2 patients had a transient response and 1 has stable disease after stopping vaccination, while 3 of them ultimately progressed.Interpretation and conclusions: The results show for the first time that the use of Id-pulsed alloDC following RIC alloSCT is safe and feasible. However, crucial strategy improvements are warranted to possibly achieve clinical benefit.