Clinical tolerance and immunologic effects after single or repeated administrations of the synthetic immunomodulator murabutide in HIV-1-infected patients
Clinical tolerance and immunologic effects after single or repeated administrations of the synthetic immunomodulator murabutide in HIV-1-infected patients
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DOI：
10.1097/00126334-200207010-00005
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发表时间：
2002-07-01
期刊：
影响因子：
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通讯作者：
Bahr, GM
中科院分区：
文献类型：
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作者：
Amiel, C;De La Tribonnière, X;Bahr, GM
纠正病毒引起的艾滋病毒感染者先天免疫缺陷很可能有助于增强免疫恢复和有效控制病毒复制。安全的合成免疫调节剂Murabutide（ISTAC Biotechnology.里尔。法国）已被发现调节抗原呈递细胞的功能，并选择性地激活CD 4淋巴细胞，从而在体外显著抑制HIV复制。因此，第一步是评估Murabutide在HIV疾病中的免疫潜力。我们已经进行了两项1/2期临床试验，以研究Murabutide给药到接受抗逆转录病毒治疗的HIV感染受试者中的安全性和免疫学效果。第一项研究显示，每剂量向6名患者单次给予5、7或9 mg Murabutide，耐受性良好。这伴随着血清中可检测到的细胞因子和趋化因子的选择性诱导，并且水平在7 mg剂量下似乎达到平台。然后，第二项研究评价了连续5天重复给予7 mg Murabutide的安全性和生物学效应。12例HIV-1感染者。整个研究期间观察到良好的临床耐受性。而且。几个免疫参数的变化。包括淋巴细胞上共受体表达的下调和淋巴增殖反应的改善。这些令人鼓舞的结果保证了在HIV感染者中使用Murabutide进行更长时间或更长周期的免疫治疗的进一步评价。
Correction of the virus-induced deficits in innate immunity of HIV-infected subjects could well contribute to enhanced immune recovery and efficacious control of viral replication. The safe synthetic immunomodulator Murabutide (ISTAC Biotechnology. Lille. France) has been found to regulate the function of antigen-presenting cells and to selectively activate CD4 lymphocytes leading to dramatic suppression of HIV replication, in vitro. Therefore, a, a first step toward the evaluation of the immunotherapeutic potential of Murabutide in HIV disease. we have conducted two phase 1/2 clinical trials to address the safety and the immunologic effects of Murabutide administration into HIV-infected subject,, receiving antiretroviral therapy, The first study revealed that single administration of 5, 7, or 9 mg of Murabutide, to 6 patients per dose, was well tolerated. This was accompanied by a selective induction of cytokines and chemokines detectable in the serum, and the levels appeared to plateau at the 7-mg dose. The second study then evaluated the safety and biological effects of repeated administrations of 7 mg Murabutide, on 5 consecutive days. in 12 HIV-1-infected patients. A good clinical tolerance as noted throughout the study. Moreover. changes in several immune parameters. including downregulation of co-receptor expression on lymphocytes and improved lymphoproliferative responses, were detected during or/and up to 3 weeks after Murabutide administration. Theseencouraging results warrant further evaluation of longer periods or cycles of immunotherapy with Murabutide in HIV-infected subjects.