Salmaggi A, Dufour A, Silvani A, Ciusani E, Nespolo A, Boiardi A
Istituto Nazionale Neurologico C. Besta, Milano, Italy.
Int J Neurosci. 1994 Jul;77(1-2):117-25. doi: 10.3109/00207459408986024.
The immunological therapy of cancer has been proposed in a number of neoplasms (Borden, Sondel, 1989; Foon, 1989; Rosenberg, 1992) and has recently been adopted in the treatment of Central Nervous System (CNS) tumors in combination with conventional surgical and radiotherapeutical approach. In this context, loco-regional administration of immunomodulating agents (for instance in post-surgical cavity) allows to achieve much higher in situ concentrations than by systemic route. Since these treatments have potential adverse effects, careful assessment of clinical and immunological parameters in phase I trials is needed. CNS tumors disseminating via Cerebrospinal Fluid (CSF) pathways offer a stimulating opportunity for intrathecal immunotherapy. In this context, alpha-IFN and IL2 (alone or in combination with LAK cells) have been employed either loco-regionally or intrathecally (Merchant, Mc Vicar, Merchant & Young, 1992; Schiller, Hank, Storer, Borchert, Moore, Albertini, Bechhofer, Wesley, Brown, Bastin & Sondel, 1993). The rationale for the use of both these substances includes the known anti-tumor action of alpha-IFN (Mahaley, Urso, Whaley, Blue, Williams, Guaspari & Selker, 1985; Nagai, 1988) and the ability of r-IL2 to generate activated cells effective in lysing tumor cell targets (Hayes, Moore, Pierz, Chen, Da Rosso, Nirenberg & Allen, 1993). We treated 3 patients (2 affected by disseminating cerebellar medulloblastoma, 1 by disseminating thalamic glioblastoma) by intrathecal r-IL2 via recervoir. In the first 2 patients, this treatment was preceded by alpha-IFN (also intrathecally). Monitoring of immunological effects of the treatment schedule involved kinetics of CSF and serum TNF-alpha, IL2s and IL2R during the first day of r-IL2 treatment, as well as on day +2 and +4 of both r-IL2 cycles, and assessment of CSF cells, protein and CSF and PB NK cell activity and CD3-CD56+ cells during the course of all treatment cycles. We also assessed clinical and neuroradiological effects of immunotherapy.
癌症的免疫疗法已在多种肿瘤中被提出（博登、桑德尔，1989年；富恩，1989年；罗森伯格，1992年），并且最近已被用于中枢神经系统（CNS）肿瘤的治疗，与传统的手术和放射治疗方法相结合。在这种情况下，局部区域给予免疫调节剂（例如在手术后的腔隙中）能够实现比全身给药途径更高的原位浓度。由于这些治疗具有潜在的不良反应，因此在I期试验中需要仔细评估临床和免疫参数。通过脑脊液（CSF）途径扩散的CNS肿瘤为鞘内免疫治疗提供了一个有启发性的机会。在这种情况下，α-干扰素和白细胞介素-2（单独或与淋巴因子激活的杀伤细胞[LAK细胞]联合使用）已被用于局部区域或鞘内给药（默钱特、麦克维卡、默钱特和扬，1992年；席勒、汉克、斯托勒、博彻特、摩尔、阿尔贝蒂尼、贝霍弗、韦斯利、布朗、巴斯廷和桑德尔，1993年）。使用这两种物质的理论依据包括已知的α-干扰素的抗肿瘤作用（马哈利、乌尔索、惠利、布卢、威廉姆斯、瓜斯帕里和塞尔克，1985年；永井，1988年）以及重组白细胞介素-2产生有效裂解肿瘤细胞靶标的活化细胞的能力（海斯、摩尔、皮尔兹、陈、达罗索、尼伦伯格和艾伦，1993年）。我们通过储液器对3例患者进行了鞘内重组白细胞介素-2治疗（2例患有播散性小脑髓母细胞瘤，1例患有播散性丘脑胶质母细胞瘤）。在前2例患者中，该治疗之前先给予了α-干扰素（也是鞘内给药）。对治疗方案的免疫效果监测包括在重组白细胞介素-2治疗的第一天以及两个重组白细胞介素-2周期的第2天和第4天，脑脊液和血清肿瘤坏死因子-α、白细胞介素-2和白细胞介素-2受体的动力学，以及在所有治疗周期过程中对脑脊液细胞、蛋白质以及脑脊液和外周血自然杀伤细胞活性和CD3-CD56+细胞的评估。我们还评估了免疫治疗的临床和神经放射学效果。
