Vaccine-induced CD4+ T cell responses to MAGE-3 protein in lung cancer patients Journal Article


Authors: Atanackovic, D.; Altorki, N. K.; Stockert, E.; Williamson, B.; Jungbluth, A. A.; Ritter, E.; Santiago, D.; Ferrara, C. A.; Matsuo, M.; Selvakumar, A.; Dupont, B.; Chen, Y. T.; Hoffman, E. W.; Ritter, G.; Old, L. J.; Gnjatic, S.
Article Title: Vaccine-induced CD4+ T cell responses to MAGE-3 protein in lung cancer patients
Abstract: MAGE-3 is the most commonly expressed cancer testis Ag and thus represents a prime target for cancer vaccines, despite infrequent natural occurrence of MAGE-3-specific immune responses in vivo. We report in this study the successful induction of Ab, CD8+, and CD4+ T cells in nonsmall cell lung cancer patients vaccinated with MAGE-3 recombinant protein. Two cohorts were analyzed: one receiving MAGE-3 protein alone, and one receiving MAGE-3 protein with adjuvant AS02B. Of nine patients in the first cohort, three developed marginal Ab titers and another one had a CD8 + T cell response to HLA-A2-restricted peptide MAGE-3 271-279. In contrast, of eight patients from the second cohort vaccinated with MAGE-3 protein and adjuvant, seven developed high-titered Abs to MAGE-3, and four had a strong concomitant CD4+ T cell response to HLA-DP4-restricted peptide 243-258. One patient simultaneously developed CD8+ T cells to HLA-A1-restricted peptide 168-176. The novel monitoring methodology used in this MAGE-3 study establishes that protein vaccination induces clear CD4 + T cell responses that correlate with Ab production. This development provides the framework for further evaluating integrated immune responses in vaccine settings and for optimizing these responses for clinical benefit.
Keywords: clinical article; controlled study; protein expression; treatment outcome; unclassified drug; human cell; drug targeting; methodology; cd8 antigen; t lymphocyte; cd8-positive t-lymphocytes; melanoma; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; neoplasm proteins; cohort analysis; lung cancer; in vivo study; drug effect; lymphocyte activation; cytokines; correlation analysis; immune response; amino acid sequence; molecular sequence data; antigens, neoplasm; cancer vaccine; cancer vaccines; melanoma antigen 3; antibody response; cd4-positive t-lymphocytes; vaccination; recombinant protein; melanoma antigen; cd4 antigen; adjuvants, immunologic; epitopes, t-lymphocyte; vaccines, dna; antibodies, neoplasm; antibody titer; saponins; peptide derivative; th2 cells; adjuvant; th1 cells; hla dp antigen; hla dp4 antigen; lipid a; humans; human; priority journal; article; adjuvant system 2b; alanylarginylglycylprolylglutamylserylarginylleucylleucylglutamylphenylalan yltyrosylleucylalanylmethionylprolylphenylalanylalanylthreonylprolylmethionylglu tamylleucylalanylarginylarginylserylleucine; glutamylvalylaspartylprolylisoleucylglycylhistidylleucyltyrosine; leucylmethionyltryptophylisoleucylthreonylglutaminylcystinylphenylalanylleu cine; lysyllysylleucylleucylthreonylglutaminylhistidylphenylalanylvalylglutaminyl glutamylasparaginyltyrosylleucylglutamyltyrosine; phenylalanylleucyltryptophylglycylprolylarginylalanylleucylvaline; phenylalanyltryptophylarginylglycylglutamylasparaginylglycylarginyllysylthr eonylarginylisoleucylalanyltyrosylglutamylarginylmethionylcysteinylasparaginylis oleucyllysylglycyllysine; vaccines, combined
Journal Title: Journal of Immunology
Volume: 172
Issue: 5
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2004-03-01
Start Page: 3289
End Page: 3296
Language: English
PROVIDER: scopus
PUBMED: 14978137
DOI: 10.4049/​jimmunol.172.5.3289
DOI/URL:
Notes: J. Immunol. -- Cited By (since 1996):112 -- Export Date: 16 June 2014 -- CODEN: JOIMA C2 - 14978137 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Mitsutoshi Matsuo
    9 Matsuo
  2. Sacha Gnjatic
    111 Gnjatic
  3. Achim Jungbluth
    340 Jungbluth
  4. Gerd Ritter
    158 Ritter
  5. Erika Ritter
    34 Ritter
  6. Bo Dupont
    156 Dupont
  7. Lloyd J Old
    385 Old