Haupt Katharina, Roggendorf Michael, Mann Klauss
Division of Clinical Chemistry, Department of Internal Medicine, University of Essen, 45122 Essen, Germany.
Exp Biol Med (Maywood). 2002 Apr;227(4):227-37. doi: 10.1177/153537020222700403.
Conventional treatment approaches for malignant tumors are highly invasive and sometimes have only a palliative effect. Therefore, there is an increasing demand to develop novel, more efficient treatment options. Increased efforts have been made to apply immunomodulatory strategies in antitumor treatment. In recent years, immunizations with naked plasmid DNA encoding tumor-associated antigens have revealed a number of advantages. By DNA vaccination, antigen-specific cellular as well as humoral immune responses can be generated. The induction of specific immune responses directed against antigens expressed in tumor cells and displayed e.g., by MHC class I complexes can inhibit tumor growth and lead to tumor rejection. The improvement of vaccine efficacy has become a critical goal in the development of DNA vaccination as antitumor therapy. The use of different DNA delivery techniques and coadministration of adjuvants including cytokine genes may influence the pattern of specific immune responses induced. This brief review describes recent developments to optimize DNA vaccination against tumor-associated antigens. The prerequisite for a successful antitumor vaccination is breaking tolerance to tumor-associated antigens, which represent "self-antigens." Currently, immunization with xenogeneic DNA to induce immune responses against self-molecules is under intensive investigation. Tumor cells can develop immune escape mechanisms by generation of antigen loss variants, therefore, it may be necessary that DNA vaccines contain more than one tumor antigen. Polyimmunization with a mixture of tumor-associated antigen genes may have a synergistic effect in tumor treatment. The identification of tumor antigens that may serve as targets for DNA immunization has proceeded rapidly. Preclinical studies in animal models are promising that DNA immunization is a potent strategy for mediating antitumor effects in vivo. Thus, DNA vaccines may offer a novel treatment for tumor patients. DNA vaccines may also be useful in the prevention of tumors with genetic predisposition. By DNA vaccination preventing infections, the development of viral-induced tumors may be avoided.
恶性肿瘤的传统治疗方法具有高度侵袭性，有时仅具有姑息作用。因此，开发新颖、更有效的治疗方案的需求日益增加。人们已加大努力将免疫调节策略应用于抗肿瘤治疗。近年来，用编码肿瘤相关抗原的裸质粒DNA进行免疫已显示出许多优势。通过DNA疫苗接种，可以产生抗原特异性的细胞免疫和体液免疫反应。针对肿瘤细胞中表达并例如由MHC I类复合物呈递的抗原诱导的特异性免疫反应可以抑制肿瘤生长并导致肿瘤排斥。提高疫苗效力已成为DNA疫苗接种作为抗肿瘤疗法开发中的关键目标。使用不同的DNA递送技术以及包括细胞因子基因在内的佐剂的共同给药可能会影响诱导的特异性免疫反应模式。这篇简短的综述描述了优化针对肿瘤相关抗原的DNA疫苗接种的最新进展。成功进行抗肿瘤疫苗接种的前提是打破对代表“自身抗原”的肿瘤相关抗原的耐受性。目前，用异种DNA进行免疫以诱导针对自身分子的免疫反应正在深入研究中。肿瘤细胞可以通过产生抗原缺失变体来形成免疫逃逸机制，因此，DNA疫苗可能有必要包含不止一种肿瘤抗原。用肿瘤相关抗原基因混合物进行多免疫接种在肿瘤治疗中可能具有协同作用。可作为DNA免疫靶点的肿瘤抗原的鉴定进展迅速。在动物模型中的临床前研究表明，DNA免疫是在体内介导抗肿瘤作用的有效策略。因此，DNA疫苗可能为肿瘤患者提供一种新疗法。DNA疫苗在预防具有遗传易感性的肿瘤方面也可能有用。通过DNA疫苗接种预防感染，可以避免病毒诱导的肿瘤的发生。
