Foa R
Dipartimento di Scienze, Biomediche e Oncologia Umana, University of Torino, Italy.
Baillieres Clin Haematol. 1994 Jun;7(2):421-34. doi: 10.1016/s0950-3536(05)80211-2.
The overall unfavourable prognosis of adult acute leukaemia patients has prompted the search for alternative therapeutic strategies. Probably the most sought challenge, which over the years has been met by consistent disillusion, has been immunotherapy. With little doubt the goal of stimulating the immune system of the host in the hope of controlling or eradicating residual disease following more conventional ablative regimens, remains conceptually a highly desirable approach. During the last few years an innovative strategy, based on the in vitro demonstration that IL2 is capable of inducing a previously unrecognized cytotoxic function directed against primary tumours and named LAK, has been applied with some success in solid tumour patients. Here, we shall review the pre-clinical data which indicate that IL2-based immunotherapy may be employed also in the management of patients with acute leukaemia. Clinical data which support a possible in vivo antileukaemic effect of IL2 are presented. The clinicohaematological modifications, as well as the biological modulations induced in the patients following the administration of IL2 are also discussed. In view of the recent demonstration that the IL2 gene can be successfully transduced into human neoplastic cells, we finally discuss the rationale of gene transfer approaches in an attempt to overcome some of the limitations associated with the administration of high doses of exogenous IL2.
成人急性白血病患者总体预后不佳，促使人们寻找替代治疗策略。多年来，免疫疗法可能是最受关注的挑战，但一直令人失望。毫无疑问，刺激宿主免疫系统以控制或根除更传统的清除性治疗方案后残留疾病的目标，在概念上仍然是一种非常理想的方法。在过去几年中，一种创新策略已在实体瘤患者中取得了一定成功，该策略基于体外实验证明白细胞介素2（IL2）能够诱导一种针对原发性肿瘤的前所未有的细胞毒性功能，即淋巴因子激活的杀伤细胞（LAK）。在此，我们将回顾临床前数据，这些数据表明基于IL2的免疫疗法也可用于急性白血病患者的治疗。文中还展示了支持IL2可能具有体内抗白血病作用的临床数据。同时讨论了给予IL2后患者的临床血液学改变以及生物学调节情况。鉴于最近已证明IL2基因可成功转导至人类肿瘤细胞，我们最后讨论了基因转移方法的基本原理，试图克服与高剂量外源性IL2给药相关的一些局限性。
