National Institute of Oncology and Radiobiology, Havana.
Cancer Manag Res. 2012;4:341-5. doi: 10.2147/CMAR.S22617. Epub 2012 Oct 5.
NeuGc-containing gangliosides have been described in melanoma cells and are an attractive target for cancer immunotherapy because they are minimally or not expressed in normal human tissues. Melanoma patients treated with a vaccine based on N-glycolyl gangliosides have shown benefit in progression free survival and overall survival. We conducted a multicenter Phase I/II clinical trial in patients with metastatic cutaneous melanoma treated with the N-gycolyl GM3/very-small-size proteoliposomes vaccine by the subcutaneous route. Selecting the optimal biological dose of the vaccine was the principal objective based on immunogenicity, efficacy, and safety results. Six dose levels were studied and the treatment schedule consisted of five doses administered every 2 weeks and then monthly until 15 doses had been given. Dose levels evaluated were 150, 300, 600, 900, 1200, and 1500 μg with five patients included in each dose level except the 900 μg dose (n = 10). Immunogenicity was determined by antibody titers generated in patients after vaccination. Antitumor effect was measured by response criteria of evaluation in solid tumors and safety was evaluated by common toxicity criteria of adverse events. The vaccine was safe and immunogenic at all doses levels. The most frequent adverse events related to vaccination were mild to moderate injection site reactions and flu-like symptoms. Vaccination induced specific anti-NeuGcGM3 immunoglobulin M and immunoglobulin G antibody responses in all patients. Disease control (objective response or stable disease) was obtained in 38.46% of patients. Global median overall survival was 20.20 months. Two patients achieved overall survival duration of about 4 and 5 years, respectively. The 900 μg dose resulted in overall survival duration of 19.40 months and was selected as the biological optimal dose.
神经节苷脂含有 NeuGc 已在黑色素瘤细胞中描述，并且是癌症免疫治疗的有吸引力的靶标，因为它们在正常人体组织中最小表达或不表达。用基于 N-糖基神经节苷脂的疫苗治疗的黑色素瘤患者在无进展生存期和总生存期方面显示出获益。我们在转移性皮肤黑色素瘤患者中进行了一项多中心 I/II 期临床试验，这些患者接受了 N-糖基 GM3/非常小尺寸脂蛋白体疫苗的皮下给药治疗。选择疫苗的最佳生物学剂量是基于免疫原性、疗效和安全性结果的主要目标。研究了六个剂量水平，治疗方案包括每 2 周给予五剂，然后每月给予一剂，直到给予 15 剂。评估的剂量水平为 150、300、600、900、1200 和 1500μg，每个剂量水平包括 5 名患者，除了 900μg 剂量（n=10）外。免疫原性通过接种后患者产生的抗体滴度来确定。抗肿瘤作用通过实体瘤评估反应标准来衡量，安全性通过不良事件的常见毒性标准来评估。该疫苗在所有剂量水平下均安全且具有免疫原性。与接种相关的最常见不良事件是轻度至中度注射部位反应和流感样症状。接种诱导了所有患者的特异性抗 NeuGcGM3 免疫球蛋白 M 和免疫球蛋白 G 抗体反应。38.46%的患者获得疾病控制（客观反应或稳定疾病）。全球中位总生存期为 20.20 个月。两名患者的总生存时间分别约为 4 年和 5 年。900μg 剂量导致总生存时间为 19.40 个月，并被选为生物学最佳剂量。
