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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)-gamma Elispot assay detecting T cells at the single cell level that secrete IFN-gamma. 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.
AuthorsJ J Lewis, S Janetzki, S Schaed, K S Panageas, S Wang, L Williams, M Meyers, L Butterworth, P O Livingston, P B Chapman, A N Houghton
JournalInternational journal of cancer (Int J Cancer) Vol. 87 Issue 3 Pg. 391-8 (Aug 01 2000) ISSN: 0020-7136 [Print] United States
PMID10897045 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
CopyrightCopyright 2000 Wiley-Liss, Inc.
Chemical References
  • Autoantigens
  • Cancer Vaccines
  • HLA-A2 Antigen
  • Neoplasm Proteins
  • Peptide Fragments
  • Monophenol Monooxygenase
Topics
  • Adult
  • Autoantigens (immunology)
  • CD8-Positive T-Lymphocytes
  • Cancer Vaccines (therapeutic use)
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HLA-A2 Antigen (immunology)
  • Humans
  • Immunotherapy, Active
  • Lymphocyte Count
  • Male
  • Melanoma (immunology, pathology, therapy)
  • Middle Aged
  • Monophenol Monooxygenase (immunology)
  • Neoplasm Metastasis
  • Neoplasm Proteins (immunology)
  • Peptide Fragments (chemical synthesis, immunology)
  • Pilot Projects
  • Reference Values

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