Delivery of tumor associated antigens to antigen presenting cells using penetratin induces potent immune responses.
Cytoplasmic delivery of proteins or CTL epitopes is crucial for the presentation of antigen for the generation of CTL. We previously described the use of the 16-amino acid peptide penetratin from the Drosophila Antennapedia domain (Int) to transport CTL epitopes into cells. Here we show that, Int, incorporating MUC1 CTL epitopes in tandem is able to facilitate their rapid uptake by macrophages and dendritic cells (DC) in an energy-dependent endocytic pathway. We also demonstrate for the first time that Int conjugated proteins are also able to be efficiently taken up by DC. Furthermore, C57BL/6 and HLA-A2 transgenic mice immunized with the Int-peptides or Int-proteins induce strong IFN-gamma secreting T cells and weak IgG1 antibodies. Immunized C57BL/6 mice were protected against the growth of a MUC1(+) tumor cell line.
Apostolopoulos
Vasso
V
The Austin Research Institute, Kronheimer Building, Studley Road, Heidelberg, Vic. 3084, Australia. v.apostolopoulos@ari.unimelb.edu.au
Pouniotis
Dodie S
DS
van Maanen
Peter J
PJ
Andriessen
Rene W
RW
Lodding
Jodie
J
Xing
Pei-Xiang
PX
McKenzie
Ian F C
IF
Loveland
Bruce E
BE
Pietersz
Geoffrey A
GA
D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D017951:Antigen Presentation; D019496:Cancer Vaccines / Q000276:immunology*; D002352:Carrier Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D018396:Mucin-1 / Q000276:immunology* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D007074:Immunoglobulin G; D018396:Mucin-1; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma; C414409:penetratin