Adding cytokines to monoclonal antibody therapy: does the concurrent administration of interleukin-12 add to the efficacy of rituximab in B-cell non-hodgkin lymphoma?
Adding cytokines to monoclonal antibody therapy: does the concurrent administration of interleukin-12 add to the efficacy of rituximab in B-cell non-hodgkin lymphoma?
复制标题
在单克隆抗体治疗中添加细胞因子：同时给予白细胞介素 12 是否会增加利妥昔单抗治疗 B 细胞非霍奇金淋巴瘤的疗效？
DOI：
10.1080/1042819031000083325
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发表时间：
2003
影响因子：
2.6
通讯作者：
Ansell,StephenM
中科院分区：
文献类型：
--
作者：
Ansell,StephenM
白细胞介素-12（IL-12）是促进细胞溶解性T细胞应答、增强NK细胞的溶解活性并诱导T细胞和NK细胞分泌干扰素-γ的细胞因子。利妥昔单抗（一种嵌合鼠/人单克隆抗体）与B淋巴细胞上的CD 20结合可诱导细胞凋亡，抗体的Fc结构域可募集免疫效应子功能以介导细胞裂解。因此，在患有B细胞非霍奇金淋巴瘤（NHL）的患者中将IL-12与利妥昔单抗组合可增强由利妥昔单抗诱导的免疫介导的细胞溶解。为了确定当IL-12与利妥昔单抗联合给药时是否存在协同效应，正在进行临床试验以评估该组合的临床功效。这两种药物联合使用时，可显著上调患者的免疫机制。该组合上调γ干扰素和IP-10表达并增加NK细胞裂解活性。该组合似乎具有显著的临床活性，在早期临床试验中具有高临床应答率。然而，需要一项随机对照试验来确定IL-12的加入是否增加了利妥昔单抗在B细胞NHL中的疗效。
Interleukin-12 (IL-12) is a cytokine that facilitates cytolytic T-cell responses, enhances the lytic activity of NK cells and induces the secretion of interferon-gamma by both T and NK cells. Binding of rituximab, a chimeric murine/human monoclonal antibody, to CD20 on B-lymphocytes induces apoptosis and the Fc domain of the antibody recruits immune effector functions to mediate cell lysis. Therefore, combining IL-12 with rituximab in patients with B-cell non-Hodgkin lymphoma (NHL) may augment the immune mediated cell lysis induced by rituximab. To determine whether a synergistic effect exists when IL-12 is given in combination with rituximab, clinical trials are being done to evaluate the clinical efficacy of the combination. The two agents, when given in combination, significantly upregulate the patient's immune mechanisms. The combination upregulates gamma interferon and IP-10 expression and increases NK cell lytic activity. The combination appears to have significant clinical activity with a high clinical response rate in early phase clinical trials. However, a randomized controlled trial will be required to determine whether the addition of IL-12 adds to the efficacy of rituximab in B-cell NHL.