Chada Sunil, Mhashilkar Abner, Roth Jack A, Gabrilovich Dmitry
Introgen Therapeutics Inc, 2250 Holcombe Boulevard, Houston, TX 77030, USA.
Curr Opin Drug Discov Devel. 2003 Mar;6(2):169-73.
Active immunotherapy using dendritic cells (DCs) to deliver tumor antigens has generated considerable excitement among oncologists worldwide. Although most tumor antigens used in immunotherapeutic approaches are tumor-associated, often, little is known about the underlying biology of the target. Here, we review the use of 'obligate' tumor antigens, where antigen expression is a prerequisite for tumor formation or maintenance. The prototype for this class of antigens is the p53 tumor antigen, which is mutated in > 50% of human malignancies. The direct involvement of p53 in the malignant transformation of tumors makes it an attractive target for immunotherapy. p53-Reactive antibodies have been found in patients with various types of cancer, demonstrating that the human immune system can recognize and respond to tumor-associated p53. Extensive preclinical experimentation has now validated the translation of p53-expressing DCs into a clinical setting. Clinical trials are ongoing to evaluate the safety and antitumor responses elicited by DCs transduced with adenoviral-p53 in cancer patients.
利用树突状细胞（DC）递送肿瘤抗原的主动免疫疗法在全球肿瘤学家中引起了相当大的关注。尽管免疫治疗方法中使用的大多数肿瘤抗原都是肿瘤相关的，但通常对靶点的潜在生物学特性知之甚少。在这里，我们回顾“必需”肿瘤抗原的应用，这类抗原的表达是肿瘤形成或维持的先决条件。这类抗原的原型是p53肿瘤抗原，它在超过50%的人类恶性肿瘤中发生突变。p53直接参与肿瘤的恶性转化，使其成为免疫治疗的一个有吸引力的靶点。在患有各种癌症的患者中发现了p53反应性抗体，这表明人类免疫系统可以识别并对肿瘤相关的p53作出反应。广泛的临床前实验现已证实将表达p53的DC应用于临床的可行性。目前正在进行临床试验，以评估癌症患者中经腺病毒-p53转导的DC引发的安全性和抗肿瘤反应。
