Hersey P, Hasic E, MacDonald M, Edwards A, Spurling A, Coates A S, Milton G W, McCarthy W H
Br J Cancer. 1985 Jun;51(6):815-26. doi: 10.1038/bjc.1985.127.
Studies were initiated to assess the response of patients with disseminated melanoma to recombinant alpha interferon (rIFN-alpha A) and to monitor effects of rIFN-alpha A on several tests of immune function. Twenty patients were treated with rIFN-alpha A given by i.m. injection in escalating doses from 15 to 50 X 10(6) um-2. The responses of two patients were considered unevaluable. Of the remainder there was complete remission of tumour in two and stable disease in two. Subsequent progression of tumour in one of the latter patients coincided with development of antibodies to IFN. Side effects (usually fatigue) were dose rate limiting in 11 patients. Laboratory tests on samples taken 6 hours after rIFN-alpha A indicated a marked lymphopenia and a reduction in natural killer (NK) cell activity particularly against K562 target cells. Longer term changes measured in samples taken 2 days after the previous rIFN-alpha A injections consisted of neutropenia and an increase in the T4/T8 ratio due mainly to a relative increase in OKT4 positive T cells compared to OKT8 positive T cells. NK activity against the K562 target cell increased in most patients during the first week of treatment and then returned to below or near pretreatment levels thereafter against the K562 target cell. This contrasted with NK activity against the melanoma target cell which showed a more gradual increase over the duration of the treatment in 6 patients. The latter correlated with an increase in mitogen stimulated IL 2 production from their blood lymphocytes and may indicate that the cytotoxic activity resulted from lymphokine-activated killer (LAK) cells. These results confirm the activity of rIFN-alpha A against melanoma in certain patients. They suggest that further studies are needed to select patients who may respond to rIFN-alpha A and to optimize treatment regimens. Tests of IL 2 production and LAK activity may assisted in achieving these objectives.
开展了多项研究，以评估播散性黑色素瘤患者对重组α干扰素（rIFN-αA）的反应，并监测rIFN-αA对多项免疫功能测试的影响。20例患者接受了rIFN-αA治疗，通过肌肉注射给予，剂量从15至50×10⁶单位/平方米逐步递增。有2例患者的反应被认为无法评估。其余患者中，2例肿瘤完全缓解，2例病情稳定。后一例患者肿瘤随后进展，同时出现了针对干扰素的抗体。11例患者的副作用（通常为疲劳）限制了剂量率。在给予rIFN-αA 6小时后采集的样本进行的实验室检测显示，明显的淋巴细胞减少，自然杀伤（NK）细胞活性降低，尤其是针对K562靶细胞。在前一次rIFN-αA注射2天后采集的样本中测量的长期变化包括中性粒细胞减少，以及T4/T8比值增加，这主要是由于与OKT8阳性T细胞相比，OKT4阳性T细胞相对增加。在治疗的第一周，大多数患者针对K562靶细胞的NK活性增加，此后针对K562靶细胞的活性恢复到低于或接近治疗前水平。这与针对黑色素瘤靶细胞的NK活性形成对比，在6例患者中，该活性在治疗期间呈更逐渐的增加。后者与丝裂原刺激的其血液淋巴细胞产生的IL-2增加相关，可能表明细胞毒性活性由淋巴因子激活的杀伤（LAK）细胞引起。这些结果证实了rIFN-αA在某些患者中对黑色素瘤的活性。它们表明需要进一步研究以选择可能对rIFN-αA有反应的患者并优化治疗方案。IL-2产生和LAK活性的测试可能有助于实现这些目标。
