Th2-dominated antitumor immunity induced by DNA immunization with the genes coding for a basal core peptide PDTRP and GM-CSF.
Our previous study showed that DNA vaccination with a plasmid vector encoding a core peptide of mucin1 (PDTRP) provided modest protection against challenge with tumor cells that expressed mucin1 protein. We report here that a DNA vaccine comprising a modified PDTRP plasmid and GM-CSF coding sequence at the C-terminus induced better protection against tumor challenge. The increased protection was directly correlated with a stronger PDTRP-specific immune response induced by the GM-CSF fusion plasmid. The plasmid encoding GM-CSF and the target PDTRP antigen induced a greater PDTRP-specific Th proliferation, antibodies, and cytotoxicity. Interestingly, the modified plasmid vaccine predominantly enhanced the type 2 immune responses manifested by an increased IgG1 to IgG2a antibody ratio and a greater induction of GATA-3 and IL-4 mRNA than that of T-bet and IFN-gamma mRNA in spleen cells from vaccinated mice. In addition, protection against tumor challenge in vaccinated mice showed that there was no significant change in mice survival after in vivo CD8+CTL depletion, indicating that antitumor immunity augmented by plasmid encoding GM-CSF and target PDTRP gene vaccine was dominated by Th2 immune response.
Chu
Y
Y
Department of Immunology, Key Laboratory of Molecular Medicine of Ministry of Education, Shanghai Medical College of Fudan University, Shanghai, China.
Xia
M
M
Lin
Y
Y
Li
A
A
Wang
Y
Y
Liu
R
R
Xiong
S
S
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D018396:Mucin-1; D009077:Mucins / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D013154:Spleen / Q000737:chemistry / Q000276:immunology; D020825:T-Box Domain Proteins; D018418:Th2 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use; D000098815:T-bet Transcription Factor
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D007074:Immunoglobulin G; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D019444:Vaccines, DNA; C511532:gamma1neo-PDTRP-GM-CSF; D015847:Interleukin-4; D007371:Interferon-gamma