Rare naturally occurring immune responses to three epitopes from the widely expressed tumour antigens hTERT and CYP1B1 in multiple myeloma patients

B. Maecker, M. S. Von Bergwelt-Baildon, K. S. Anderson, R. H. Vonderheide, K. C. Anderson, L. M. Nadler, Joachim L. Schultze

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The widely expressed tumour antigens hTERT and CYP1B1 are commonly expressed in multiple myeloma (MM) cells. Several trials targeting these antigens by immunotherapy have been initiated. The aim of this study was to explore whether patients with MM have an endogenous pre-existing immune response against recently identified epitopes from hTERT and CYP1B1. Peripheral blood T cells from 27 HLA-A*0201+ multiple myeloma patients at different stages of disease and 20 healthy HLA-A*0201+ donors were enriched and studied for the presence of hTERT- and CYP1B1-specific cytotoxic T cells using MHC tetramer detection and short-term ex vivo expansion. No significant expansion of tetramer-positive cells was detected in the peripheral blood of either MM patients or healthy controls when cells were stained with tetramers containing the dominant hTERT-derived epitope or two peptides derived from CYP1B1. A single ex vivo peptide stimulation led to the detection of a small population (0.3-0.5%) of hTERT-specific cells in two of 27 patients with MM. None of the patients or controls showed significant expansion of CYP1B1-specific cells after a single peptide stimulation. Thus, endogenous in vivo priming of T cells against hTERT and CYP1B1 is a rare event in MM patients. These results suggest that strategies targeting hTERT and CYP1B1 may have to utilize techniques to induce T cell responses from a naive precursor frequency.

Original languageEnglish (US)
Pages (from-to)558-562
Number of pages5
JournalClinical and Experimental Immunology
Volume141
Issue number3
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

Keywords

  • CYP1B1
  • Immunotherapy
  • T cell immunity
  • Tumour antigen
  • hTERT

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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