Lambda phage nanoparticles displaying HER2-derived E75 peptide induce effective E75-CD8+ T response

被引:30
作者
Arab, Atefeh [1 ]
Nicastro, Jessica [2 ,3 ]
Slavcev, Roderick [2 ,3 ,4 ]
Razazan, Atefeh [5 ]
Barati, Nastaran [1 ]
Nikpoor, Amin Reza [6 ]
Brojeni, Amir Abbas Momtazi [7 ]
Mosaffa, Fatemeh [1 ]
Badiee, Ali [8 ]
Jaafari, Mahmoud Reza [8 ]
Behravan, Javad [1 ,2 ]
机构
[1] Mashhad Univ Med Sci, Pharmaceut Technol Inst, Biotechnol Res Ctr, Mashhad, Iran
[2] Univ Waterloo, Sch Pharm, 200 Univ Ave, Waterloo, ON N2L 3G1, Canada
[3] Univ Waterloo, Waterloo Inst Nanotechnol, 200 Univ Ave, Waterloo, ON N2L 3G1, Canada
[4] Mediphage Bioceut Inc, MaRS Ctr, 661 Univ Ave,Suite 1300,West Tower, Toronto, ON M5G 0B7, Canada
[5] Univ Tehran Med Sci, Sch Adv Technol Med, Dept Mol Med, Tehran, Iran
[6] Mashhad Univ Med Sci, Sch Med, Dept Immunol, Mashhad, Iran
[7] Mashhad Univ Med Sci, Student Res Comm, Mashhad, Iran
[8] Mashhad Univ Med Sci, Pharmaceut Technol Inst, Nanotechnol Res Ctr, Mashhad, Iran
基金
加拿大自然科学与工程研究理事会;
关键词
Phage display; E75; peptide; Lambda (lambda); lambda F7; HER2/neu protein; VACCINE DESIGN; CELLS; EPITOPE; IMMUNITY; DELIVERY; ANTIGEN; VIRUS; FOXP3; MICE; MELANOMA;
D O I
10.1007/s12026-017-8969-0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
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.
引用
收藏
页码:200 / 206
页数:7
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