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)-╬│Elispot assay detecting T cells at the single cell level that secrete IFN-╬│. 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
Notes: Export Date: 18 November 2015 -- Source: Scopus
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MSK Authors
  1. Jonathan J Lewis
    107 Lewis
  2. Siqun Wang
    9 Wang
  3. Susanne G Schaed
    5 Schaed
  4. Paul Chapman
    259 Chapman
  5. Katherine S Panageas
    332 Panageas
  6. Alan N Houghton
    274 Houghton
  7. Michael L Meyers
    16 Meyers