Parkinson D R
Department of Clinical Immunology and Biological Therapy, University of Texas, M.D. Anderson Cancer Center, Houston.
Nat Immun Cell Growth Regul. 1990;9(4):242-52.
The initial results of interleukin-2 (IL-2) therapy in man are reviewed from the perspective of how they conform to predictions from preclinical studies. These preclinical models predict that tumors will vary in their susceptibility to IL-2 therapy and will be most successfully treated at lower tumor burdens. In addition, the dose and schedule of IL-2 are important for successful therapy. Host-related factors, including the presence of suppressor activities, may also be important. In these models, the addition of other cytokines, including interferon-alpha or tumor necrosis factor, to IL-2 can enhance antitumor activity. The concomitant administration of ex vivo IL-2-activated lymphokine-activated killer cells or tumor-infiltrating lymphocytes also enhances the IL-2 antitumor effect. Clinical trials addressing all of these issues have been completed or are underway; the results suggest overall that the preclinical models are predictive, with both host- and tumor-related factors as well as such IL-2-therapy-related factors as dose, schedule, route and the use of additional agents all playing a role in the success of therapy. A more complete understanding of the mechanisms of response and resistance involved in this therapy will facilitate the rational development of more effective and less toxic IL-2-based therapy of human malignancy.
从白细胞介素-2（IL-2）疗法在人体中的初步结果如何符合临床前研究预测的角度进行了综述。这些临床前模型预测，肿瘤对IL-2疗法的敏感性会有所不同，且在较低肿瘤负荷时治疗最为成功。此外，IL-2的剂量和给药方案对成功治疗也很重要。包括抑制活性存在与否在内的宿主相关因素可能也很重要。在这些模型中，将其他细胞因子，包括α干扰素或肿瘤坏死因子，添加到IL-2中可增强抗肿瘤活性。体外IL-2激活的淋巴因子激活的杀伤细胞或肿瘤浸润淋巴细胞的联合给药也可增强IL-2的抗肿瘤作用。针对所有这些问题的临床试验已经完成或正在进行；结果总体表明，临床前模型具有预测性，宿主和肿瘤相关因素以及诸如剂量、给药方案、途径和使用其他药物等与IL-2疗法相关的因素均在治疗成功中发挥作用。对该疗法中反应和耐药机制的更全面理解将有助于合理开发更有效且毒性更低的基于IL-2的人类恶性肿瘤治疗方法。
