Bellone Matteo, Mondino Anna, Corti Angelo
Cancer Immunotherapy and Gene Therapy Program, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy.
Trends Immunol. 2008 May;29(5):235-41. doi: 10.1016/j.it.2008.02.003. Epub 2008 Mar 28.
Chemotherapy has been combined with therapeutic tumor-specific vaccination in an attempt to simultaneously debulk tumors, increase the effector lymphocyte:tumor cell ratio, and favor immune-mediated tumor rejection. However, chemotherapy is often inadequate because of insufficient and uneven drug penetration into tumors, and because it might also cause, in some instances, undesirable side effects and immunosuppression. Here, we suggest a combined approach based on targeted alteration of the endothelial barrier function with vascular disrupting agents, such as tumor necrosis factor-alpha (TNF-alpha), before chemotherapy and tumor-specific vaccination. This approach has the potential to empower chemoimmunotherapeutic strategies by improving cytotoxic drug penetration into tumors while exploiting the proinflammatory and immunostimulating activities of TNF-alpha and active immunotherapy.
化疗已与治疗性肿瘤特异性疫苗接种相结合，试图同时使肿瘤体积缩小、提高效应淋巴细胞与肿瘤细胞的比例，并促进免疫介导的肿瘤排斥反应。然而，由于药物对肿瘤的渗透不足且不均匀，化疗往往效果不佳，而且在某些情况下，化疗还可能引起不良副作用和免疫抑制。在此，我们提出一种联合方法，即在化疗和肿瘤特异性疫苗接种之前，使用血管破坏剂（如肿瘤坏死因子-α （TNF-α））有针对性地改变内皮屏障功能。这种方法有可能通过改善细胞毒性药物对肿瘤的渗透，同时利用TNF-α的促炎和免疫刺激活性以及主动免疫疗法，增强化学免疫治疗策略。
