Brooks Nicole, Esparon Sandra, Pouniotis Dodie, Pietersz Geoffrey A
School of Medical Sciences, RMIT University, Plenty Road, Bundoora 3083, Victoria, Australia.
Bio-Organic and Medicinal Chemistry Laboratory, Centre for Biomedical Research, Burnet Institute, 85 Commercial Rd, Melbourne 3004, Australia.
Molecules. 2015 Aug 3;20(8):14033-50. doi: 10.3390/molecules200814033.
Cell penetrating peptides (CPP), including the TAT peptide from the human immunodeficiency virus transactivator of transcription (HIV-TAT) protein and penetratin from Drosophila Antennapedia homeodomain protein, translocate various cargos including peptides and proteins across cellular barriers. This mode of delivery has been harnessed by our group and others to deliver antigenic proteins or peptides into the cytoplasm of antigen processing cells (APC) such as monocyte-derived dendritic cells (MoDC). Antigens or T cell epitopes delivered by CPP into APC in vivo generate antigen-specific cytotoxic T cell and helper T cell responses in mice. Furthermore, mice immunised with these peptides or proteins are protected from a tumour challenge. The functional properties of CPP are dependent on the various cargos being delivered and the target cell type. Despite several studies demonstrating superior immunogenicity of TAT and Antp-based immunogens, none has compared the immunogenicity of antigens delivered by TAT and Antp CPP. In the current study we demonstrate that a cytotoxic T cell epitope from the mucin 1 (MUC1) tumour associated antigen, when delivered by TAT or Antp, generates identical immune responses in mice resulting in specific MUC1 T cell responses as measured by in vivo CTL assays, IFNγ ELISpot assays and prophylactic tumour protection.
细胞穿透肽(CPP),包括来自人类免疫缺陷病毒转录激活因子(HIV-TAT)蛋白的TAT肽和来自果蝇触角足同源结构域蛋白的穿膜肽,可使包括肽和蛋白质在内的各种货物穿过细胞屏障。我们小组和其他研究团队利用这种递送方式将抗原性蛋白质或肽递送至抗原加工细胞(APC)如单核细胞衍生的树突状细胞(MoDC)的细胞质中。通过CPP在体内递送至APC的抗原或T细胞表位可在小鼠体内产生抗原特异性细胞毒性T细胞和辅助性T细胞反应。此外,用这些肽或蛋白质免疫的小鼠可免受肿瘤攻击。CPP的功能特性取决于所递送的各种货物和靶细胞类型。尽管有多项研究表明基于TAT和Antp的免疫原具有卓越的免疫原性,但尚无研究比较TAT和Antp CPP递送抗原的免疫原性。在本研究中,我们证明,粘蛋白1(MUC1)肿瘤相关抗原的细胞毒性T细胞表位,经TAT或Antp递送后,在小鼠体内产生相同的免疫反应,通过体内CTL测定、IFNγ ELISpot测定和预防性肿瘤保护检测,可产生特异性MUC1 T细胞反应。
In Silico Pharmacol. 2024-9-18
Proc Natl Acad Sci U S A. 2022-8-9
Int J Mol Sci. 2022-6-13
Cell Mol Life Sci. 2018-3-5
Mol Ther Nucleic Acids. 2017-9-15
Nat Rev Immunol. 2014-9-5
Front Immunol. 2014-5-30
J Control Release. 2013-12-1
J Drug Deliv. 2013
FEBS Lett. 2013-5-10
Trends Immunol. 2013-3-27
Annu Rev Immunol. 2013-1-3