Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells
Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells
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DOI：
10.1182/blood-2004-11-4558
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发表时间：
2005-10-01
期刊：
影响因子：
20.3
通讯作者：
Dummer, R
中科院分区：
文献类型：
--
作者：
Heinzerling, L;Künzi, V;Dummer, R
一些皮肤T细胞淋巴瘤（CTCL）克隆T细胞缺乏干扰素信号传导，使其成为有希望的病毒溶瘤靶点。我们评估了麻疹病毒（MV）在CTCL中的细胞病变效应。CTCL细胞系和CTCL中的浸润淋巴细胞表达MV受体CD 150和CD 46。在一项I期剂量递增试验中，5例CTCL患者接受了总计16次活MV（Edmonston-Zagreb疫苗株）瘤内注射。患者具有抗麻疹血清抗体，并接受干扰素a预治疗，以防止病毒不受控制地传播。MV的良好耐受性治疗导致临床反应。在注射前和注射后11天，通过免疫组织化学和逆转录酶-聚合酶链反应（RT-PCR）对活检进行评价，结果显示局部病毒活性，MV核蛋白（NP）染色阳性，干扰素γ（IFN-γ）/CD 4和IFN-γ/CD 8 mRNA比值增加，CD 4/CD 8比值降低。所有患者治疗后抗麻疹抗体滴度均升高。数据表明，CTCL是基于MV的溶瘤疗法的有希望的靶标。
Some cutaneous T-cell lymphomas, (CTCLs) clonal T cells are deficient in interferon signaling, making them promising targets for viral oncolysis. We evaluated cytopathic effects of measles virus (MV) in CTCL. CTCL cell lines and infiltrating lymphocytes in CTCL expressed MV receptors CD150 and CD46. In a phase 1 dose escalation trial a total of 16 injections of live MV, Edmonston-Zagreb vaccine strain, were given intratumorally to 5 patients with CTCL. Patients had anti-measles-serum antibodies and were pretreated with interferon-a to prevent uncontrolled virus spread. The well-tolerated treatment with MV resulted in clinical responses. Evaluation of biopsies, before and at 11 days after injection, by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated local viral activity with positive staining for MV nucleoprotein (NP), an increase of the interferon gamma (IFN-gamma)/CD4 and IFN-gamma/CD8 mRNA ratios and a reduced CD4/CD8 ratio. All patients demonstrated an increased antimeasles antibody titer after therapy. The data demonstrate that CTCLs are promising targets for an MV-based oncolytic therapy.