Gribben John G, Riches John C
1Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
Hematology Am Soc Hematol Educ Program. 2013;2013:151-7. doi: 10.1182/asheducation-2013.1.151.
Although there have been recent advances with targeted therapies in chronic lymphocytic leukemia (CLL), chemoimmunotherapy remains the treatment of choice; however, this approach is not curative. A key feature of CLL is that it induces a state of immunosuppression, causing increased susceptibility to infections and failure of an antitumor immune response, often worsened by the immunosuppressive effect of treatment. Because of its improved specificity, immunotherapy potentially offers a way out of this dilemma. Allogeneic stem cell transplantation remains the only curative option, but is hampered by the toxicity of GVHD. After many years of promise but little reward, many other immunotherapeutic approaches are now in transition to the clinical setting. Clinical trials including CLL vaccines, CXCR4 antagonists, and adoptive cellular immunotherapies such as chimeric antigen receptor-modified T cells, CD40 ligand gene therapy, and the immunomodulatory drug lenalidomide are ongoing. Results to date suggest that immunotherapeutic approaches for the treatment of CLL might finally be fulfilling their promise.
尽管近年来慢性淋巴细胞白血病（CLL）的靶向治疗取得了进展，但化学免疫疗法仍是首选治疗方法；然而，这种方法无法治愈疾病。CLL的一个关键特征是它会引发免疫抑制状态，导致对感染的易感性增加以及抗肿瘤免疫反应失败，而治疗的免疫抑制作用往往会使这种情况恶化。由于免疫疗法具有更高的特异性，它有可能为摆脱这一困境提供一条出路。异基因干细胞移植仍然是唯一的治愈选择，但受到移植物抗宿主病（GVHD）毒性的阻碍。在经历了多年的期望但收获寥寥之后，许多其他免疫治疗方法目前正处于向临床应用过渡的阶段。包括CLL疫苗、CXCR4拮抗剂以及嵌合抗原受体修饰的T细胞、CD40配体基因疗法和免疫调节药物来那度胺等过继性细胞免疫疗法在内的临床试验正在进行。迄今为止的结果表明，用于治疗CLL的免疫治疗方法最终可能会实现其承诺。
