非小细胞肺癌疫苗治疗的临床研究进展

Advance in clinical research of non-small cell lung cancer vaccines

非小细胞肺癌(non-small cell lung cancer,NSCLC)的疫苗治疗具有不良反应小、耐受性好的特点,但众多的临床研究并未取得突破性的进展。影响疫苗治疗肺癌的主要困难包括由于肿瘤免疫原性弱而缺乏肿瘤特异性抗原以及宿主免疫监视下的肿瘤免疫逃逸和免疫耐受。近几年来,随着人们对肿瘤和免疫系统关系的进一步认识,特异性肿瘤抗原的发现及免疫佐剂和载体的发展,疫苗治疗NSCLC已经取得了显著的进展,如melanoma-associated antigen-A3疫苗、针对mucin 1抗原的疫苗、EGF疫苗等抗原特异性疫苗以及将TGF-β2转染NSCLC细胞株制成的全细胞疫苗Belagenpumatucel-L等。多个Ⅱ期临床研究已经证实了它们在NSCLC中的疗效,相应多中心的Ⅲ期临床研究正在进行中。

The therapeutic cancer vaccines have low toxicity and well tolerance. However, many clinical studies of vaccines for NSCLC have not made significant progress. The major difficulties in the development of therapeutic cancer vaccines include the lack of tumor specific antigen, the tumor escape mechanisms from host immune surveillance and immune tolerance. In recent years, new insights in the interaction between tumors and the immune system, the better identification of antigenic targets, the addition of immunoadjuvants and the production of more efficient delivery systems have resulted in more sophisticated vaccines, such as antigen-specific vaccines targeting mela- noma-associated antigen-A3, mucin 1 and EGF, and whole-cell vaccines such as belagenpumatucel-L. These vaccines have shown promising results in phase 11 clinical trials, and need to be evaluated in Phase m clinical trials.