Establishment of animal models to analyze the kinetics and distribution of human tumor antigen-specific CD8+ T cells Journal Article


Authors: Muraoka, D.; Nishikawa, H.; Noguchi, T.; Wang, L.; Harada, N.; Sato, E.; Luescher, I.; Nakayama, E.; Kato, T.; Shiku, H.
Article Title: Establishment of animal models to analyze the kinetics and distribution of human tumor antigen-specific CD8+ T cells
Abstract: Many patients develop tumor antigen-specific T cell responses detectable in peripheral blood mononuclear cells (PBMCs) following cancer vaccine. However, measurable tumor regression is observed in a limited number of patients receiving cancer vaccines. There is a need to re-evaluate systemically the immune responses induced by cancer vaccines. Here, we established animal models targeting two human cancer/testis antigens, NY-ESO-1 and MAGE-A4. Cytotoxic T lymphocyte (CTL) epitopes of these antigens were investigated by immunizing BALB/c mice with plasmids encoding the entire sequences of NY-ESO-1 or MAGE-A4. CD8+ T cells specific for NY-ESO-1 or MAGE-A4 were able to be detected by ELISPOT assays using antigen presenting cells pulsed with overlapping peptides covering the whole protein, indicating the high immunogenicity of these antigens in mice. Truncation of these peptides revealed that NY-ESO-1-specific CD8+ T cells recognized Dd-restricted 8mer peptides, NY-ESO-181-88. MAGE-A4-specific CD8+ T cells recognized Dd-restricted 9mer peptides, MAGE-A4265-273. MHC/peptide tetramers allowed us to analyze the kinetics and distribution of the antigen-specific immune responses, and we found that stronger antigen-specific CD8+ T cell responses were required for more effective anti-tumor activity. Taken together, these animal models are valuable for evaluation of immune responses and optimization of the efficacy of cancer vaccines. Ā© 2013 Elsevier Ltd.
Keywords: animal model; cancer vaccine; translational research; cacer/testis antigens; cd8+ t cells; immune responses
Journal Title: Vaccine
Volume: 31
Issue: 17
ISSN: 0264-410X
Publisher: Elsevier Inc.  
Date Published: 2013-04-19
Start Page: 2110
End Page: 2118
Language: English
PROVIDER: scopus
PUBMED: 23499606
DOI: 10.1016/j.vaccine.2013.02.056
DOI/URL:
Notes: --- - "Export Date: 1 May 2013" - "CODEN: VACCD" - ":doi 10.1016/j.vaccine.2013.02.056" - "Source: Scopus"
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