IMMUNOMOD EFFECTS OF RECOMBINANT GAMMA IFN IN PATIENTS WITH MALIGNANT MELANOMA

多种生物反应调节剂的临床前研究 已经表明更高的药物剂量不一定与 具有更大程度的免疫调节或抗肿瘤 方面的影响. 肿瘤反应与BRM剂量的关系曲线呈钟形 形状使得最佳调节在通常良好的剂量下发生 低于最大耐受剂量。 在这项研究中，我们试图 确定γ的最佳生物反应调节剂量 干扰素治疗微小肿瘤恶性黑色素瘤患者 负担 选择这组患者进行本研究，以便 将癌症对免疫参数的影响降到最低 来监测这项研究。 免疫学参数 这项研究包括自然杀伤细胞活性，过氧化氢， 单核细胞的产生，以及Fc表达的变化 受体和外周血单核细胞上的HLA-DR。 以下 肌内注射γ干扰素后， 在剂量高于0.01 mg/m2时观察到这些参数， 似乎在0.1 mg/m2剂量下达到最大值。 剂量接近 最大耐受剂量为0.25 mg/m2，尽管过氧化氢 产量有所提高，但在过去一年中大幅下降， 干扰素给药周。 我们得出的结论是，在人类中， 在动物中，存在一个最佳的生物学反应调整剂量， 低于MTD的重组干扰素γ。 抗肿瘤 该最佳生物反应调节剂量的活性应 在这个患者群体中进行评估。

Preclinical studies of many biological response modifying agents have indicated that higher drug doses do not necessarily correlate with greater degrees of either immune modulation or antitumor effects. The curve relating tumor responses to BRM dose is bell shaped such that optimal modulation occurs at doses usually well below the maximally tolerated dose. In this study we attempted to determine the optimal biologic response modifying dose of gamma interferon in patients with malignant melanoma with minimal tumor burden. This group of patients was chosen for this study so as to minimize the effects of cancer on the immune parameters we wished to monitor for this study. Immunological parameters followed in this study included natural killer cell activity, hydrogen peroxide production by monocytes, and changes in the expression of Fc receptors and HLA-DR on peripheral blood monocytes. Following intramuscular administration of gamma interferon, changes in all of these parameters were seen at doses above 0.01 mg/m2 and appeared to be maximized at the 0.1 mg/m2 dose. At a dose near the maximally tolerated dose, 0.25 mg/m2, although hydrogen peroxide production was enhanced, it declined significantly during the last week of interferon administration. We conclude that in humans, as in animals, there is an optimal biologic response modifying dose of recombinant interferon gamma below the MTD. The antitumor activity of this optimal biologic response modifying dose should be evaluated in this patient population.