Fredman Pam, Hedberg Kristina, Brezicka Thomas
Experimental Neuroscience Section, Institute of Clinical Neuroscience, The Sahlgrenska Institute at Göteborg University, Sahlgrenska University Hospital, SE 43180 Molndal, Sweden.
BioDrugs. 2003;17(3):155-67. doi: 10.2165/00063030-200317030-00002.
Gangliosides, sialic acid-containing glycosphingolipids, have engendered great interest for more than 20 years in the search for target molecules of relevance for tumour growth and formation of metastases and as potential targets for immunotherapy. These molecules show large quantitative and structural variability, which is related to cell type and developmental stage. Their potential role in the formation of tumour metastases was suggested from data supporting that they are involved in cell growth regulation and in cell-cell and cell-matrix adhesion. Moreover, gangliosides are expressed on the cell surface and thereby are accessible for antibodies or other ganglioside-binding molecules to induce cell death, inhibit cell growth and/or inhibit formation of tumour metastasis. All tumours exhibit aberrant ganglioside expression. This includes overexpression of normal ganglioside constituents, which appears to be common among various tumours, and expression of gangliosides not found in normal adult tissue but often found during fetal development. The ganglioside composition of melanoma cells has been found to correlate with their metastatic potential and also to be selectively expressed in cells of a tumour mass and invading tumour cells. Passive immunotherapy using murine or murine/human chimeric monoclonal antiganglioside antibodies in their native form or combined with various effector molecules has been investigated. However, the vaccination strategy using native or structurally modified tumour-associated gangliosides in combination with adjuvants is currently the dominant method in clinical trials. The outcomes reported so far vary between type of tumour and treatment strategies. However, we believe that targeting gangliosides is as promising as any other immune therapeutic strategy, and basic research as well as clinical trials utilising new aspects is encouraged.
神经节苷脂是含唾液酸的糖鞘脂，在寻找与肿瘤生长和转移形成相关的靶分子以及作为免疫治疗的潜在靶点方面，二十多年来一直备受关注。这些分子在数量和结构上表现出很大的变异性，这与细胞类型和发育阶段有关。它们在肿瘤转移形成中的潜在作用是基于支持它们参与细胞生长调节以及细胞间和细胞与基质粘附的数据而提出的。此外，神经节苷脂在细胞表面表达，因此抗体或其他神经节苷脂结合分子可以与之结合，从而诱导细胞死亡、抑制细胞生长和/或抑制肿瘤转移的形成。所有肿瘤都表现出异常的神经节苷脂表达。这包括正常神经节苷脂成分的过表达，这在各种肿瘤中似乎很常见，以及在正常成人组织中未发现但在胎儿发育期间经常发现的神经节苷脂的表达。已发现黑色素瘤细胞的神经节苷脂组成与其转移潜能相关，并且在肿瘤块细胞和侵袭性肿瘤细胞中选择性表达。已经研究了使用天然形式的鼠源或鼠/人嵌合单克隆抗神经节苷脂抗体或与各种效应分子结合的被动免疫疗法。然而，目前在临床试验中占主导地位的方法是使用天然或结构修饰的肿瘤相关神经节苷脂与佐剂联合的疫苗接种策略。迄今为止报道的结果因肿瘤类型和治疗策略而异。然而，我们认为靶向神经节苷脂与任何其他免疫治疗策略一样有前景，鼓励开展利用新方面的基础研究以及临床试验。
