Lambda phage nanoparticles displaying HER2-derived E75 peptide induce effective E75-CD8+ T response
Lambda phage nanoparticles displaying HER2-derived E75 peptide induce effective E75-CD8+ T response
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DOI：
10.1007/s12026-017-8969-0
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发表时间：
2018-02-01
影响因子：
4.4
通讯作者：
Behravan, Javad
中科院分区：
文献类型：
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作者：
Arab, Atefeh;Nicastro, Jessica;Behravan, Javad
我们已经研究了在BALB/c小鼠的可植入TUBO乳腺肿瘤模型中展示E75肽（源自HER 2蛋白）的λ（lambda）噬菌体颗粒的体外免疫原性和体内预防和治疗潜力。在6周的时间内，每隔2周用展示E75的噬菌体（λ F7-gpD：：E75）免疫小鼠，并研究产生的免疫应答。结果显示，与对照λ F7和缓冲液组相比，λ F7（gpD：：E75）构建体体外诱导免疫应答。在体内预防研究中，所有对照组和接种疫苗的小鼠组均出现肿瘤。然而，在治疗性实验中，我们观察到与对照组相比，用λ F7（gpD：：E75）免疫的小鼠在第14-36天的肿瘤大小的显著差异（P < 0.05）。此外，用λ F7（gpD：：E75）免疫的小鼠的存活时间延长。从体外和体内研究获得的结果之间的差异可能是Foxp 3 CD 4（+）CD 25（+）诱导的结果，先前已报道Foxp 3 CD 4（+）CD 25（+）会阻碍有效的T细胞功能。总之，我们在体外研究中观察到显著的免疫刺激应答，而在体内，疫苗不能发挥显著的肿瘤抑制作用。我们认为Foxp 3（+）CD 4（+）CD 25（+）细胞的存在可能损害了体内用TUBO异种移植肿瘤攻击的小鼠的抗肿瘤应答。
We have investigated the in vitro immunogenicity and in vivo prophylactic and therapeutic potential of lambda (lambda) phage particles displaying the E75 peptide (derived from HER2 protein) in an implantable TUBO breast tumor model of BALB/c mice. The mice were immunized with the E75-displaying phage (lambda F7-gpD::E75) every 2-week intervals over a 6-week period, and the generated immune responses were studied. Results showed in vitro induction of immune responses by the lambda F7 (gpD::E75) construct compared to the control lambda F7 and buffer groups. In the in vivo prophylactic study, all the control and vaccinated mice groups developed tumors. However, in the therapeutic experiments, we observed a significant difference in tumor size at days 14-36 for mice immunized with lambda F7 (gpD::E75) compared to control groups (P < 0.05). Moreover, the survival time prolonged in mice immunized with lambda F7 (gpD::E75). The discrepancy between the results obtained from the in vitro and in vivo studies may have been a result of the induction of Foxp3 CD4(+)CD25(+) which has been previously reported to hamper effective T cell functionality. In conclusion, we observed a significant immune stimulatory response in the in vitro study, while in vivo, the vaccine was not able to exert significant tumor inhibitory effects. We suggest that the presence of Foxp3(+) CD4(+)CD25(+) cells may have impaired the anti-tumor response in mice challenged in vivo with the TUBO xenograft tumor.