Analysis of peripheral and local anti-tumor immune response in esophageal cancer patients after NY-ESO-1 protein vaccination Journal Article
| Authors: | Wada, H.; Sato, E.; Uenaka, A.; Isobe, M.; Kawabata, R.; Nakamura, Y.; Iwae, S.; Yonezawa, K.; Yamasaki, M.; Miyata, H.; Doki, Y.; Shiku, H.; Jungbluth, A. A.; Ritter, G.; Murphy, R.; Hoffman, E. W.; Old, L. J.; Monden, M.; Nakayama, E. |
| Article Title: | Analysis of peripheral and local anti-tumor immune response in esophageal cancer patients after NY-ESO-1 protein vaccination |
| Abstract: | NY-ESO-1 antigen is a prototype of a class of cancer/testis antigens. We carried out a clinical trial using NY-ESO-1 whole protein as a cancer vaccine for 13 advanced cancer patients. We have recently reported that vaccine elicited humoral and cellular immune responses in 9 cancer patients including 4 esophageal cancer patients, and clinical responses were also observed in 4 of 5 evaluable patients. In this study, we analyzed the responses in 8 esophageal cancer patients including 4 newly enrolled patients. Patients were injected subcutaneously at biweekly intervals with NY-ESO-1 recombinant protein formulated with cholesterol-bearing hydrophobized pullulan. Induction of antibody, and CD4 and CD8 T-cell responses were observed in 7, 7 and 6 patients, respectively, out of 8 patients. 1 PR, 2 SD and 2 mixed clinical responses were observed in 6 evaluable patients. No significant adverse events were observed. Furthermore, we analyzed NY-ESO-1 and MHC class I expression and the infiltration of immune cells into tumor samples obtained before and after vaccination from 4 patients by immunohistochemistry. The results showed 2 patients with disappearance of CD4 and CD8 T-cell infiltration, 1 patient with increase in the number of CD68+ macrophages and 1 patient with tumor antigen loss in the progressive tumors following vaccinations. The induction of NY-ESO-1 immunity and some preferable clinical outcomes were observed in esophageal cancer patients by vaccination with NY-ESO-1. However, the tumors grew eventually by various mechanisms after vaccination. © 2008 Wiley-Liss, Inc. |
| Keywords: | immunohistochemistry; clinical article; human tissue; protein expression; treatment response; unclassified drug; clinical feature; clinical trial; cancer patient; outcome assessment; cd8 antigen; cd8+ t lymphocyte; protein analysis; cell infiltration; membrane proteins; tumor antigen; pruritus; immunology; cellular immunity; immune response; antigens, neoplasm; cancer vaccine; cancer vaccines; antibody response; cancer immunization; cd4+ t lymphocyte; ctag1b protein, human; membrane protein; recombinant protein; pullulan; skin induration; phase 1 clinical trial; cd4 antigen; tumor growth; macrophage; esophagus cancer; injection site erythema; immunocompetent cell; esophagus tumor; esophageal neoplasms; esophageal cancer; drug formulation; major histocompatibility antigen class 1; cd68 antigen; immunity, cellular; ny-eso-1; antigen loss; cholesterol bearing hydrophobized pullulan ny eso 1 vaccine; ny eso 1 protein |
| Journal Title: | International Journal of Cancer |
| Volume: | 123 |
| Issue: | 10 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2008-11-15 |
| Start Page: | 2362 |
| End Page: | 2369 |
| Language: | English |
| DOI: | 10.1002/ijc.23810 |
| PUBMED: | 18729190 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 12" - "Export Date: 17 November 2011" - "CODEN: IJCNA" - "Source: Scopus" |
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