Evaluation of CD8(+) T-cell frequencies by the Elispot assay in healthy individuals and in patients with metastatic melanoma immunized with tyrosinase peptide Journal Article
| Authors: | Lewis, J. J.; Janetzki, S.; Schaed, S.; Panageas, K. S.; Wang, S.; Williams, L.; Meyers, M.; Butterworth, L.; Livingston, P. O.; Chapman, P. B.; Houghton, A. N. |
| Article Title: | Evaluation of CD8(+) T-cell frequencies by the Elispot assay in healthy individuals and in patients with metastatic melanoma immunized with tyrosinase peptide |
| Abstract: | The lack of reproducible, quantitative assays for T-cell responses has been a limitation in the development of cancer vaccines to elicit T-cell immunity. We utilized the Elispot assay, which allows a quantitative and functional assessment of T cells directed against specific peptides after only brief in vitro incubations. CD8+ T-cell reactivity was determined with an interferon (IFN)-γElispot assay detecting T cells at the single cell level that secrete IFN-γ. We studied both healthy individuals and patients with melanoma. Healthy HLA-A*0201-positive individuals showed a similar mean frequency of CD8+ cells recognizing a tyrosinase peptide, YMDGTMSQV, when compared with melanoma patients prior to immunization. The frequencies of CD8+ cells recognizing the tyrosinase peptide remained relatively constant over time in healthy individuals. Nine HLA-A*0201-positive patients with stage IV metastatic melanoma were immunized intradermally with the tyrosinase peptide together with the immune adjuvant QS-21 in a peptide dose escalation study with 3 patients per dose group. Two patients demonstrated a significant increase in the frequency of CD8+ cells recognizing the tyrosinase peptide during the course of immunization, from approx. 1/16,000 CD8+ T cells to approx. 1/4,000 in the first patient and from approx. 1/14,000 to approx. 1/2,000 in the second patient. These results demonstrate that modest expansion of peptide-specific CD8+ T cells can be generated in vivo by immunization with peptide plus QS-21 in at least a subset of patients with melanoma. (C) 2000 Wiley-Liss, Inc. |
| Keywords: | adult; clinical article; controlled study; middle aged; clinical trial; cd8 antigen; cd8-positive t-lymphocytes; quantitative assay; melanoma; metastasis; controlled clinical trial; neoplasm proteins; tumor antigen; enzyme linked immunosorbent assay; cellular immunity; gamma interferon; cancer vaccines; pilot projects; antigen recognition; cancer immunization; peptide fragments; reference values; neoplasm metastasis; autoantigens; tumor immunity; phase 1 clinical trial; monophenol monooxygenase; enzyme-linked immunosorbent assay; hla a antigen; t lymphocyte subpopulation; lymphocyte count; hla-a2 antigen; qs 21; melanoma vaccine; immunotherapy, active; humans; human; male; female; priority journal; article; nonapeptide |
| Journal Title: | International Journal of Cancer |
| Volume: | 87 |
| Issue: | 3 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2000-08-01 |
| Start Page: | 391 |
| End Page: | 398 |
| Language: | English |
| DOI: | 10.1002/1097-0215(20000801)87:3<391::aid-ijc13>3.0.co;2-k |
| PUBMED: | 10897045 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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