Efficient in vivo priming by vaccination with recombinant NY-ESO-1 protein and CpG in antigen naïve prostate cancer patients Journal Article
| Authors: | Karbach, J.; Neumann, A.; Atmaca, A.; Wahle, C.; Brand, K.; Von Boehmer, L.; Knuth, A.; Bender, A.; Ritter, G.; Old, L. J.; Jager, E. |
| Article Title: | Efficient in vivo priming by vaccination with recombinant NY-ESO-1 protein and CpG in antigen naïve prostate cancer patients |
| Abstract: | Purpose: NY-ESO-1, one of the most immunogenic tumor antigens, is expressed in 15% to 25% of metastatic prostate cancers. The immunological and clinical effects of vaccination with recombinant NY-ESO-1 protein combined with CpG as adjuvant were evaluated. Experimental Design: In a phase I clinical study, patients with advanced prostate cancer were vaccinated with recombinant NY-ESO-1 protein (100 mg) mixed with CpG 7909 (2.5 mg) every 3 weeks intradermally for 4 doses. Objectives of the study were the safety of the vaccine and changes of specific humoral and cellular immunological responses to NY-ESO-1 in relation to detectable NY-ESO-1 expression in the individual tumor. Results: All 12 baseline sero-negative patients developed high-titer NY-ESO-1 antibody responses. B-cell epitope mapping identified NY-ESO-1 p91-110 to be recognized most frequently by vaccine-induced antibodies. Two patients developed significant antibody titers against the adjuvant CpG. NY-ESO-1-specific CD4+ and/or CD8+ T-cell responses were induced in 9 patients (69%). Five of these 9 patients did not express NY-ESO-1 in the autologous tumor. Postvaccine CD8+ T-cell clones recognized and lyzed HLA-matched tumor cell lines in an antigen-specific manner. Conclusion: Our data provide clear evidence for the capacity of NY-ESO-1 protein/CpG vaccine to induce integrated antigen-specific immune responses in vivo and to efficiently prime CD8+T-cell responses in NY-ESO-1 antigen-negative patients. Our results may also support further clinical vaccination protocols with NY-ESO-1 protein not only focused on the treatment of existing cancer, but also to prevent further development of NY-ESO-1 positive cancers in vivo. ©2010 AACR. |
| Keywords: | clinical article; protein expression; unclassified drug; drug safety; adjuvant therapy; antigen expression; cd8+ t lymphocyte; in vivo study; drug effect; b lymphocyte; prostate cancer; rash; hypotension; hla matching; cellular immunity; antigen specificity; recombinant antigen; cancer immunization; cd4+ t lymphocyte; epitope mapping; agatolimod; tumor cell line; phase 1 clinical trial; humoral immunity; injection site erythema; antibody; hypersensitivity reaction; antibody titer; clone; blister; swelling; injection site pruritus; recombinant ny eso 1 protein; injection site necrosis |
| Journal Title: | Clinical Cancer Research |
| Volume: | 17 |
| Issue: | 4 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2011-02-15 |
| Start Page: | 861 |
| End Page: | 870 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-10-1811 |
| PROVIDER: | scopus |
| PUBMED: | 21163871 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 23 June 2011" - "CODEN: CCREF" - "Source: Scopus" |
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