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Vaccine-Induced CD4+ T Cell Responses to MAGE-3 Protein in Lung Cancer Patients

2004; American Association of Immunologists; Volume: 172; Issue: 5 Linguagem: Inglês

10.4049/jimmunol.172.5.3289

1550-6606

Djordje Atanackovic, Nasser K. Altorki, Elisabeth Stockert, Barbara Williamson, Achim A. Jungbluth, Erika Ritter, Darren Santiago, Cathy A. Ferrara, Mitsutoshi Matsuo, Annamalai Selvakumar, Bo Dupont, Yao-Tseng Chen, Eric W. Hoffman, Gerd Ritter, Lloyd J. Old, Sacha Gnjatic,

Immune Cell Function and Interaction

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.