免疫接种含有突变 K-Ras 肽的纳米疫苗和咪喹莫特会加重在小鼠中诱导的异位胰腺癌。

PURPOSE: The growing incidence and lethality of pancreatic cancer urges the development of new therapeutic approaches. Anti-tumoral vaccines can potentiate the immune response against the tumor, targeting specific antigens expressed only on tumor cells. In this work, we designed new vaccines for pancreatic cancer, composed by chitosan nanocapsules (CS NCs) containing imiquimod (IMQ) as adjuvant, and targeting the K-Ras mutation G12V. EXPERIMENTAL DESIGN: We tested the immunogenicity of our vaccines in mice, carrying different combinations of K-Ras mutated peptides. Then, we analyzed their prophylactic and therapeutic efficacy in mice bearing heterotopic pancreatic cancer. RESULTS: Unexpectedly, although good results were observed at short time points, the different combinations of our CS NCs vaccines seemed to potentiate tumor growth and reduce survival rate. We propose that this effect could be due to an inadequate immune response, partially because of the induction of a regulatory tolerogenic response. CONCLUSION: Our results call for caution in the use of some NCs containing IMQ in the immunotherapy against pancreatic cancer.

目的：胰腺癌的发病率和致死率不断上升，促使人们开发新的治疗方法。抗肿瘤疫苗可以增强针对肿瘤的免疫反应，针对仅在肿瘤细胞上表达的特定抗原。在这项工作中，我们设计了新的胰腺癌疫苗，由载有异维 A 酸（IMQ）作为佐剂的壳聚糖纳米胶囊（CS NCs）组成，针对 K-Ras 突变 G12V。

实验设计：我们在携带不同组合的 K-Ras 突变肽的小鼠中测试了我们疫苗的免疫原性，然后分析了它们在携带异位胰腺癌的小鼠中的预防和治疗效果。

结果：出乎意料的是，尽管在短时间内观察到了良好的结果，但我们的 CS NCs 疫苗的不同组合似乎增强了肿瘤的生长并降低了存活率。我们提出，这种效应可能是由于免疫反应不足引起的，部分原因是诱导了调节性耐受反应。

结论：我们的结果呼吁在使用含有 IMQ 的一些 NCs 进行胰腺癌的免疫治疗时要谨慎。