Transgene S,A,, Boulevard Gonthier d'Andernach, Parc d'Innovation, 67405 Cedex Illkirch Graffenstaden, France.
J Transl Med. 2013 Sep 25;11:226. doi: 10.1186/1479-5876-11-226.
Primary cutaneous lymphomas (CLs), characterized by an accumulation of clonal T or B lymphocytes preferentially localized in the skin, have been successfully treated with interferons (IFNs) which counterbalance the Th2-immunosuppressive state associated with this pathology. In a phase I/II clinical trial, we correlated the local immune infiltrate and the anti-tumor effects of repeated intralesional administrations of an adenovirus vector expressing human interferon-gamma (IFN-g) termed TG1042, in patients with advanced primary cutaneous T-cell lymphomas (CTCL) or multilesional cutaneous B-cell lymphomas (CBCL).
For each patient, variation in time of specific lymphocyte populations, defined by immunohistochemical stainings, was assessed in biopsies of injected lesions. For each patient, the change in local immune response was associated with the patient's objective response at the end of the study.
Immunohistochemical analyses of biopsies indicate that infiltration of CD8+ T lymphocytes and of TIA-1+ cytotoxic T-cells in lesions injected with TG1042 correlates with clinical benefit.
These data suggest for the first time that a CD8+ cytotoxic infiltrate, induced by local expression of IFN-g correlates with a clinical response.
The phase I step (TG1042.01) does not have a registration number. The phase II step (TG1042.06) registration number was NCT00394693.
原发性皮肤淋巴瘤（CL）的特征是克隆性 T 或 B 淋巴细胞在皮肤中优先聚集，已成功接受干扰素（IFNs）治疗，这些药物可平衡与该病理学相关的 Th2 免疫抑制状态。在一项 I/II 期临床试验中，我们在晚期原发性皮肤 T 细胞淋巴瘤（CTCL）或多发性皮肤 B 细胞淋巴瘤（CBCL）患者中，将表达人干扰素-γ（IFN-γ）的腺病毒载体 TG1042 局部重复给药，对局部免疫浸润和抗肿瘤作用进行了相关性分析。
对于每个患者，通过免疫组化染色定义的特定淋巴细胞群在注射病变活检中的时间变化进行了评估。对于每个患者，局部免疫反应的变化与研究结束时患者的客观反应相关联。
对 TG1042 注射病变活检的免疫组织化学分析表明，CD8+ T 淋巴细胞和 TIA-1+细胞毒性 T 细胞的浸润与临床获益相关。
这些数据首次表明，由局部表达 IFN-γ诱导的 CD8+细胞毒性浸润与临床反应相关。
I 期（TG1042.01）部分无注册编号。II 期（TG1042.06）部分的注册编号为 NCT00394693。
