Morecki S, Revel-Vilk S, Nabet C, Pick M, Ackerstein A, Nagler A, Naparstek E, Ben Shahar M, Slavin S
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Cancer Immunol Immunother. 1992;35(6):401-11. doi: 10.1007/BF01789019.
Immunological parameters were evaluated in patients treated with cytokine-mediated immunotherapy (CMI) consisting of low doses of recombinant human interferon alpha 2a (rIFN alpha) and recombinant human interleukin-2 (rIL-2) administered either concomitantly or sequentially by subcutaneous self-injections in an outpatient setting. Twenty-six patients with hematological malignancies and 2 metastatic melanoma patients in a progressive stage were enrolled in this clinical trial. Of the 26 patients, 24 were at a stage of minimal residual disease, including 14 patients who had received autologous bone marrow transplantation (ABMT) 2-5 months previously, 7 chronic myelogenous leukemia (CML) and 3 acute myeloid leukemia (AML) patients. Two patients (1 CML and 1 mult. myeloma) were treated at a stage of progressive disease. Non-MHC-restricted cytotoxicity directed against natural-killer(NK)-resistant (Daudi) and NK-sensitive (K562) target cells was assessed before, during and after CMI, either in fresh peripheral blood samples (spontaneous activity) or after in vitro rIL-2 activation (induced activity). Spontaneous killing activity was low prior to treatment, but increased upon termination of treatment in 10/15 evaluated cycels. rIL-2-activated cytotoxicity in vitro was markedly elevated in 8/12 and 6/8 patients after one and two cycles, respectively, of sequential treatment, as well as in 3/8 CML and 5/6 patients after one and two cycles, respectively, of concomitant treatment. Activation of the T cell mitogenic response was demonstrated in 6/9 patients after concomitant CMI, while no such effect was observed throughout a sequential treatment in lymphoma and leukemia patients after ABMT. Although a direct correlation between immune stimulation and the in vivo antitumor response cannot yet be determined, our clinical observations support a beneficial therapeutic effect in a substantial number of patients. These results indicated that the ambulatory CMI protocol of rIL-2 and rIFN alpha could stimulate the host defense immune system and may be helpful in mediating the in vivo antitumor response in patients with minimal residual disease.
在门诊环境中，对接受细胞因子介导免疫疗法（CMI）治疗的患者进行了免疫参数评估。该疗法由低剂量重组人干扰素α2a（rIFNα）和重组人白细胞介素-2（rIL-2）组成，通过皮下自我注射同时或序贯给药。26例血液系统恶性肿瘤患者和2例处于进展期的转移性黑色素瘤患者参加了这项临床试验。26例患者中，24例处于微小残留病阶段，其中14例在2至5个月前接受了自体骨髓移植（ABMT），7例慢性粒细胞白血病（CML）患者和3例急性髓细胞白血病（AML）患者。2例患者（1例CML和1例多发性骨髓瘤）在疾病进展阶段接受治疗。在CMI治疗前、治疗期间和治疗后，对针对自然杀伤（NK）抗性（Daudi）和NK敏感（K562）靶细胞的非MHC限制性细胞毒性进行了评估，评估对象为新鲜外周血样本（自发活性）或体外rIL-2激活后（诱导活性）。治疗前自发杀伤活性较低，但在10/15个评估周期中，治疗结束时活性增加。在序贯治疗的1个周期和2个周期后，分别有8/12例和6/8例患者的体外rIL-2激活细胞毒性显著升高，在联合治疗的1个周期和2个周期后，分别有3/8例CML患者和5/6例患者的体外rIL-2激活细胞毒性显著升高。在联合CMI治疗后，6/9例患者出现T细胞有丝分裂反应激活，而在ABMT后的淋巴瘤和白血病患者的序贯治疗中未观察到这种效应。虽然免疫刺激与体内抗肿瘤反应之间的直接相关性尚无法确定，但我们的临床观察支持在相当数量的患者中具有有益的治疗效果。这些结果表明，rIL-2和rIFNα的门诊CMI方案可以刺激宿主防御免疫系统，并可能有助于介导微小残留病患者的体内抗肿瘤反应。
