Live-attenuated bacterial vectors for antigens delivery have aroused growing interest in the field of cancer immunotherapy. Their potency to stimulate innate immunity and to promote intracellular antigen delivery into antigen-presenting cells could be exploited to elicit a strong and specific cellular immune response against tumor cells. We previously described genetically-modified and attenuated Pseudomonas aeruginosa vectors able to deliver in vivo protein antigens into antigen-presenting cells, through Type 3 secretion system of the bacteria. Using this approach, we managed to protect immunized mice against aggressive B16 melanoma development in both a prophylactic and therapeutic setting. In this study, we further investigated the antigen-specific CD8+ T cell response, in terms of phenotypic and functional aspects, obtained after immunizations with a killed but metabolically active P. aeruginosa attenuated vector. We demonstrated that P. aeruginosa vaccine induces a highly functional pool of antigen-specific CD8+ T cell able to infiltrate the tumor. Furthermore, multiple immunizations allowed the development of a long-lasting immune response, represented by a pool of predominantly effector memory cells which protected mice against late tumor challenge. Overall, killed but metabolically active P. aeruginosa vector is a safe and promising approach for active and specific antitumor immunotherapy.

中文翻译：

---

通过安全的减毒铜绿假单胞菌载体引发的多功能和持久抗癌免疫应答。

用于抗原递送的减毒活细菌载体引起了癌症免疫治疗领域的日益增长的兴趣。可以利用它们刺激先天免疫并促进细胞内抗原传递到抗原呈递细胞中的能力来引发针对肿瘤细胞的强而特异性的细胞免疫应答。我们先前描述了经过基因修饰和减毒的铜绿假单胞菌载体，能够通过细菌的3型分泌系统将体内蛋白抗原传递到抗原呈递细胞中。使用这种方法，我们设法在预防和治疗环境中保护免疫小鼠免受侵袭性B16黑色素瘤的发展。在这项研究中，我们从表型和功能方面进一步研究了抗原特异性CD8 + T细胞反应，用灭活但具有代谢活性的铜绿假单胞菌减毒载体免疫后获得。我们证明了铜绿假单胞菌疫苗诱导了能够浸润肿瘤的抗原特异性CD8 + T细胞的高功能库。此外，多次免疫可以产生持久的免疫反应，以主要的效应记忆细胞池为代表，这些记忆细胞可以保护小鼠免受晚期肿瘤的攻击。总体而言，已杀死但具有代谢活性的铜绿假单胞菌载体是用于主动和特异性抗肿瘤免疫疗法的安全且有前途的方法。多次免疫可以产生持久的免疫应答，以主要的效应记忆细胞为代表，这些记忆细胞可以保护小鼠免受晚期肿瘤的攻击。总体而言，已杀死但具有代谢活性的铜绿假单胞菌载体是用于主动和特异性抗肿瘤免疫疗法的安全且有希望的方法。多次免疫可以产生持久的免疫应答，以主要的效应记忆细胞为代表，这些记忆细胞可以保护小鼠免受晚期肿瘤的攻击。总体而言，已杀死但具有代谢活性的铜绿假单胞菌载体是用于主动和特异性抗肿瘤免疫疗法的安全且有前途的方法。