Unit of Immuno-Biotherapy of Melanoma and Solid Tumors, San Raffaele Foundation Scientific Institute, Milan, Italy.
Cancer J. 2011 Sep-Oct;17(5):331-6. doi: 10.1097/PPO.0b013e3182337a76.
Devitalized tumor cells either autologous or allogeneic have been used as anti-cancer vaccines with the purpose of facilitating the induction of an immune response able to destroy growing tumor cells since the identification of tumor antigens was deemed not to be necessary, particularly in the autologous system. Such vaccines were tested first in animal models and then in the clinics as unmodified tumor cells or after insertion of genes coding for factors known to increase the immune response against tumors. These vaccines were usually given by subcutaneous injections along with different immunological adjuvants. Such immunization approaches were found to be effective in mice when carried out in a tumor preventive setting but significantly less in the therapeutic context, that is, in the presence of an established tumor. By analyzing several clinical trials of vaccination using either autologous or allogeneic unmodified and gene-modified tumor cells published in the last 10 to 15 years, we conclude for a lack of sufficient evidence for efficacy of this strategy in inducing both a strong immune response and a therapeutic response. A potential variant of this strategy is the direct intratumoral injection of immunostimulatory genes delivered by vectors in vivo. But even this approach failed to provide a statistically significant clinical benefit for the cancer patients.We also point out the inherent drawbacks of the tumor cell-based vaccine strategy that include (a) a limited frequency by which human tumor lines can be obtained from clinical samples, (b) the low number of available cells for vaccination, (c) the release of immune-suppressive factors by tumor cells, and (d) the cost and time necessary for standardization and collecting/expanding a number of cells according to the approved regulatory requirements. Thus, taking into consideration the new developments in cancer vaccines, we believe that tumor cell-based vaccines should be dismissed as anti-cancer vaccines unless a clear benefit could be demonstrated by the few ongoing trials of combination with new immunomodulating reagents (eg, anti-CTLA4, PD-1, chemotherapy).
失活的肿瘤细胞，无论是自体的还是同种异体的，已被用作抗癌疫苗，其目的是促进诱导能够破坏生长中的肿瘤细胞的免疫反应，因为鉴定肿瘤抗原被认为是不必要的，特别是在自体系统中。这些疫苗首先在动物模型中进行了测试，然后在临床上作为未经修饰的肿瘤细胞或在插入编码已知能增加对肿瘤免疫反应的因子的基因后进行了测试。这些疫苗通常通过皮下注射与不同的免疫佐剂一起使用。在预防性肿瘤环境中进行这种免疫接种在小鼠中被发现是有效的，但在治疗环境中，即存在已建立的肿瘤时，效果明显降低。通过分析过去 10 到 15 年发表的关于使用自体或同种异体未经修饰和基因修饰的肿瘤细胞进行疫苗接种的几项临床试验，我们得出结论，缺乏足够的证据表明这种策略在诱导强烈的免疫反应和治疗反应方面有效。这种策略的一个潜在变体是直接向肿瘤内注射免疫刺激基因，这些基因通过载体在体内传递。但即使这种方法也未能为癌症患者提供统计学上显著的临床益处。我们还指出了基于肿瘤细胞的疫苗策略的固有缺陷，包括 (a) 从临床样本中获得人类肿瘤系的频率有限，(b) 用于接种的可用细胞数量少，(c) 肿瘤细胞释放免疫抑制因子，以及 (d) 标准化和根据批准的监管要求收集/扩大一定数量细胞所需的成本和时间。因此，考虑到癌症疫苗的新发展，我们认为，除非正在进行的与新免疫调节试剂（例如抗 CTLA4、PD-1、化疗）联合使用的少数试验能够证明明确的益处，否则基于肿瘤细胞的疫苗应被视为抗癌疫苗。
