Mucosal vaccination with phage-displayed tumour antigens identified through proteomics-based strategy inhibits the growth and metastasis of 4T1 breast adenocarcinoma.
Cancer immunotherapy relies on the identification and characterization of tumour antigens that can be recognized by effector T cells. Here, we used a proteomics-based approach to identify tumour antigens recognized by serum antibodies from patients with breast cancer. Specific reactivity against a set of spots was identified and their identity was revealed by MALDI-TOF peptide mass fingerprinting. They include disintegrin and metalloprotease 10, aldolase A, beta-ATPase F1, heat shock protein 27, deaminase, pyruvate dehydrogenase protein X component, and Vimentin. Western blot analysis using recombinant proteins expressed in E. coli confirmed the specific reactivity with patient sera. Several tumour antigens were expressed on the surface of the T7 phage and shown to trigger specific immune responses in BALB/c mice following oral immunisation. Furthermore, these immune responses inhibited tumour growth and metastasis of the 4T1 mammary adenocarcinoma cell line. Collectively, the present data indicate that proteomics-based strategy can identify tumour antigens whose surface display on phages or bacteria can provide an effective strategy for mucosal cancer vaccines. In addition, arrayed phage-displayed tumour antigens could be useful as a serum-based screening test for the detection of several tumour antigens.
Shadidi
Mohsen
M
Department of Immunology, Molecular Medicine Group, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Montebello, N-0310 Oslo, Norway.
Sørensen
Dag
D
Dybwad
Anne
A
Furset
Gro
G
Sioud
Mouldy
M
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000284:Administration, Oral; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D019151:Peptide Library; D040901:Proteomics; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D019151:Peptide Library; D014614:Vaccines, Synthetic