Menez-Jamet Jeanne, Kosmatopoulos Kostas
Vaxon Biotech, 3-5 impasse Reille, 75014, Paris, France.
IDrugs. 2009 Feb;12(2):98-102.
Specific immunotherapy is based on the use of tumor-specific antigens to induce an efficient antitumor immune response. Although tumors are known to be weakly immunogenic and therefore capable of escaping immune surveillance, the objective of tumor vaccination is to induce a frequent, strong and long-lasting antitumor immune response based mainly on the activation of cytotoxic T-lymphocytes. However, as widely expressed tumor antigens (universal tumor antigens) often correspond to normal proteins expressed not only by tumor cells but also by normal cells and tissues, these antigens are generally tolerated by the immune system. Thus, circumventing self tolerance to universal tumor antigens is a major goal of cancer vaccine research. Disappointing results obtained to date with most tumor vaccines has led to a shift in research toward determining ways of stimulating the immune response through the use of new adjuvants, immunostimulants and delivery vectors. However, although these aspects are clearly crucial to vaccine development, breakthroughs in the field may lie in the use of strong antigens as optimized cryptic peptides derived from universal tumor antigens, combined with a potent adjuvant. Targeting cryptic tumor peptides/antigens is an efficient way of overcoming tolerance. Indeed, the first vaccine based on an optimized cryptic peptide induced strong antitumor immunity and demonstrated promising clinical activity.
特异性免疫疗法基于使用肿瘤特异性抗原来诱导有效的抗肿瘤免疫反应。尽管已知肿瘤具有弱免疫原性，因此能够逃避免疫监视，但肿瘤疫苗接种的目标是主要基于细胞毒性T淋巴细胞的激活来诱导频繁、强烈且持久的抗肿瘤免疫反应。然而，由于广泛表达的肿瘤抗原（通用肿瘤抗原）通常对应于不仅由肿瘤细胞而且由正常细胞和组织表达的正常蛋白质，这些抗原通常会被免疫系统耐受。因此，规避对通用肿瘤抗原的自身耐受性是癌症疫苗研究的主要目标。迄今为止，大多数肿瘤疫苗取得的令人失望的结果导致研究转向确定通过使用新的佐剂、免疫刺激剂和递送载体来刺激免疫反应的方法。然而，尽管这些方面对疫苗开发显然至关重要，但该领域的突破可能在于使用强抗原，即源自通用肿瘤抗原的优化隐蔽肽，并结合强效佐剂。靶向隐蔽肿瘤肽/抗原是克服耐受性的有效方法。事实上，第一种基于优化隐蔽肽的疫苗诱导了强烈的抗肿瘤免疫力，并显示出有前景的临床活性。
