Osorio Marta, Gracia Elías, Rodríguez Edmundo, Saurez Giselle, Arango Maria Del Carmen, Noris Elena, Torriella Adriana, Joan Alejandro, Gómez Erasmo, Anasagasti Lorenzo, González Jorge Luis, Melgares María de Los Angeles, Torres Imilla, González Joel, Alonso Dayamí, Rengifo Enrique, Carr Adriana, Pérez Rolando, Fernández Luis Enrique
Clinical Trials Unit, National Institute of Oncology and Radiobiology, Havana City, Cuba.
Cancer Biol Ther. 2008 Apr;7(4):488-95. doi: 10.4161/cbt.7.4.5476. Epub 2007 Jan 2.
NeuGcGM3 ganglioside is especially attractive because it is expressed on melanoma cells but it is minimally or not expressed at all on most normal human tissues. A Phase Ib/IIa clinical trial was carried out in patients with advanced cutaneous and ocular malignant melanomas, to evaluate immunogenicity and toxicity of an intramuscularly administered cancer vaccine and composed by NeuGcGM3 in a proteoliposome of Neisseria meningitides with Montanide ISA 51 as adjuvant. Twenty two patients were included, twelve at dose level of 200 microg and 10 at 400 microg. The first five doses were administered every other week and then monthly until 9 doses. 12 patients received additional immunizations. Vaccination induced specific anti-NeuGcGM3 IgM, IgG and IgA antibodies responses. Titers of IgM were greater for the highest vaccine doses. Vaccination also elicited DTH response in 45.5% of patients in the lower doses and 77.8% in the higher doses. Toxicities were mostly grade 1 or 2, according CTC-NCI criteria. Interestingly, 3 patients developed vitiligo at the lower dose (none in the highest dose) although the nominal antigen NeuGcGM3 is not present in melanocytes. Survival analysis was not the goal of this Phase I trial; nevertheless, the fact that seven patients are alive for more than 2 years after inclusion is noteworthy. Safety and immunogenicity with NeuGcGM3 vaccine treatment in advanced melanoma patients were established. The prognostic value of autoimmunity and the possibilities of dissociating anti-tumor immunity from autoimmunity deserve further research.
NeuGcGM3神经节苷脂特别引人关注，因为它在黑色素瘤细胞上表达，但在大多数正常人体组织中表达极少或根本不表达。一项Ib/IIa期临床试验在晚期皮肤和眼部恶性黑色素瘤患者中开展，以评估一种肌肉注射的癌症疫苗的免疫原性和毒性，该疫苗由NeuGcGM3组成，包裹在含有蒙旦胺ISA 51作为佐剂的脑膜炎奈瑟菌蛋白脂质体中。纳入了22名患者，12名接受200微克剂量水平，10名接受400微克剂量水平。前5剂每隔一周给药一次，然后每月给药一次，直至9剂。12名患者接受了额外的免疫接种。疫苗接种诱导了特异性抗NeuGcGM3 IgM、IgG和IgA抗体反应。最高疫苗剂量组的IgM滴度更高。疫苗接种在低剂量组45.5%的患者和高剂量组77.8%的患者中也引发了迟发型超敏反应。根据美国国立癌症研究所（NCI）的常见毒性标准（CTC），毒性大多为1级或2级。有趣的是，低剂量组有3名患者出现了白癜风（高剂量组无），尽管黑素细胞中不存在名义抗原NeuGcGM3。生存分析并非该I期试验的目标；然而，7名患者在入组后存活超过2年这一事实值得关注。NeuGcGM3疫苗治疗晚期黑色素瘤患者的安全性和免疫原性得以确立。自身免疫的预后价值以及将抗肿瘤免疫与自身免疫分离的可能性值得进一步研究。
