Synthesis of oligosaccharides and glycoconjugates to develop anti-cancer vaccines

我们研究小组的基本专业知识在于合成碳水化合物化学。研究计划的主要目标是通过化学合成设计基于肿瘤相关碳水化合物抗原(TACA)的安全抗癌疫苗。我们的研究项目针对的是抗原：二聚体Lex、Lealex、Ley、LebLea和LeyLex(KH-1)。我们的目标是发现能够分别针对结直肠癌细胞和肺鳞癌细胞触发安全免疫反应的二聚体Lex和Lealex片段。我们还旨在通过研究一类由Ley抗原连接到两性离子多糖(PS A1)组成的新分子来提高TACA触发有效(T细胞依赖)免疫反应的能力。PS A1是从脆弱类杆菌中提取的，已被证明在不需要佐剂或载体蛋白的情况下能诱导所需的免疫反应。鉴于我们的专业知识，我们还在设计有效的合成策略来制备更具挑战性的七糖：LebLea和LeyLex(KH-1)，这两种糖都与腺癌有关。由于已证实癌细胞在细胞发育过程中表达不同水平的几种不同的TACA，我们将使用这两种抗原通过酰胺键形成和无铜点击化学来研究二价破伤风类毒素结合物的制备。

The basic expertise of our research group resides in synthetic carbohydrate chemistry. The main goal of research program is to design through chemical synthesis safe anti-cancer vaccines based on Tumor Associated Carbohydrates Antigens (TACAs). Our research program targets the antigens: dimericLex, LeaLex, Ley, LebLea and LeyLex (KH-1). We aim at discovering fragments of dimericLex and LeaLex that are able to trigger safe immune responses targeted against colorectal cancer cells and squamous lung carcinoma cells, respectively. We also aim at increasing the ability of the TACAs to trigger an efficient (T-cell dependent) immune response by investigating a new class of molecules made of the Ley antigen linked to a zwitterionic polysaccharide (PS A1). PS A1 is extracted from Bacteroides fragilis and has been shown to elicit the desired immune response without the need for an adjuvant or carrier protein. Given our expertise, we are also designing efficient synthetic strategies to prepare the more challenging heptasaccharides: LebLea and LeyLex (KH-1) which are both associated with adenocarcinomas. Because it has been well-established that cancer cells express several different TACAs at levels that vary over the course of cellular development, we will use these two antigens to investigate the preparation of divalent tetanus toxoid conjugates via amide bond formation and copper-free click chemistry.