Booster vaccination of cancer patients with MAGE-A3 protein reveals long-term immunological memory or tolerance depending on priming Journal Article
| Authors: | Atanackovic, D.; Altorki, N. K.; Cao, Y.; Ritter, E.; Ferrara, C. A.; Ritter, G.; Hoffman, E. W.; Bokemeyer, C.; Old, L. J.; Gnjatic, S. |
| Article Title: | Booster vaccination of cancer patients with MAGE-A3 protein reveals long-term immunological memory or tolerance depending on priming |
| Abstract: | We previously reported results of a phase II trial in which recombinant MAGE-A3 protein was administered with or without adjuvant AS02B to 18 non-small-cell lung cancer (NSCLC) patients after tumor resection. We found that the presence of adjuvant was essential for the development of humoral and cellular responses against selected MAGE-A3 epitopes. In our current study, 14 patients that still had no evidence of disease up to 3 years after vaccination with MAGE-A3 protein with or without adjuvant received an additional four doses of MAGE-A3 protein with adjuvant AS02B. After just one boost injection, six of seven patients originally vaccinated with MAGE-A3 protein plus adjuvant reached again their peak antibody titers against MAGE-A3 attained during the first vaccination. All seven patients subsequently developed even stronger antibody responses. Furthermore, booster vaccination widened the spectrum of CD4 + and CD8+ T cells against various new and known MAGE-A3 epitopes. In contrast, only two of seven patients originally vaccinated with MAGE-A3 protein alone developed high-titer antibodies to MAGE-A3, and all these patients showed very limited CD4+ and no CD8+ T cell reactivity, despite now receiving antigen in the presence of adjuvant. Our results underscore the importance of appropriate antigen priming using an adjuvant for generating persistent B and T cell memory and allowing typical booster responses with reimmunization. In contrast, absence of adjuvant at priming compromises further immunization attempts. These data provide an immunological rationale for vaccine design in light of recently reported favorable clinical responses in NSCLC patients after vaccination with MAGE-A3 protein plus adjuvant AS02B. © 2008 by The National Academy of Sciences of the USA. |
| Keywords: | clinical article; unclassified drug; human cell; clinical trial; cancer patient; cd8+ t lymphocyte; t lymphocyte; cd8-positive t-lymphocytes; t-lymphocytes; multiple cycle treatment; phase 2 clinical trial; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; neoplasm proteins; tumor antigen; lung tumor; blood; immunological tolerance; immunology; immune tolerance; antigens, neoplasm; cancer vaccine; cancer vaccines; melanoma antigen 3; antibody response; cancer immunization; cd4+ t lymphocyte; cd4-positive t-lymphocytes; epitope mapping; vaccination; epitope; tumor protein; memory cell; antibodies, neoplasm; antibody; non-small-cell lung cancer; antibody titer; immunization; magea3 protein, human; immunization, secondary; immunological memory; cancer antibody; adjuvant; cd4+ t cell; cd8+ t cell |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 105 |
| Issue: | 5 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2008-02-01 |
| Start Page: | 1650 |
| End Page: | 1655 |
| Language: | English |
| DOI: | 10.1073/pnas.0707140104 |
| PUBMED: | 18216244 |
| PROVIDER: | scopus |
| PMCID: | PMC2234199 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 52" - "Export Date: 17 November 2011" - "CODEN: PNASA" - "Source: Scopus" |
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