Artificial antigen-presenting cells transduced with telomerase efficiently expand epitope-specific, human leukocyte antigen-restricted cytotoxic T cells Academic Article uri icon

Overview

MeSH Major

  • Antigen-Presenting Cells
  • Epitopes, T-Lymphocyte
  • Immunotherapy, Adoptive
  • T-Lymphocytes, Cytotoxic
  • Telomerase

abstract

  • Human telomerase reverse transcriptase (hTERT) is overexpressed in most human tumors, making it a potential target for cancer immunotherapy. hTERT-derived CTL epitopes have been identified previously, including p865 (RLVDDFLLV) and p540 (ILAKFLHWL), which are restricted by the human leukocyte antigen (HLA) class I A*0201 allele. However, it remains a major challenge to efficiently and consistently expand hTERT-specific CTLs from donor peripheral blood T lymphocytes. To bypass the need for generating conventional antigen-presenting cells (APC) on an autologous basis, we investigated the potential ability of fibroblast-derived artificial APCs (AAPC) to activate and expand HLA-A*0201-restricted CTLs. We show here that AAPCs stably expressing HLA-A*0201, human beta(2)-microglobulin, B7.1, intercellular adhesion molecule-1, and LFA-3, together with either p540 and p865 minigenes or the full-length hTERT, effectively stimulate tumoricidal, hTERT-specific CTLs. hTERT-expressing AAPCs stimulated both p540 and p865 CTLs as shown by peptide-specific cytolysis and tetramer staining, indicating that hTERT is processed by the AAPCs and that the two peptides are presented as codominant epitopes. The level of cytotoxic activity against a panel of tumors comprising hematologic and epithelial malignancies varied, correlating overall with the level of HLA-A2 and hTERT expression by the target cell. Starting from 100 mL blood, approximately 100 million hTERT-specific CTLs could be generated over the course of five sequential stimulations, representing an expansion of approximately 1 x 10(5). Our data show that AAPCs process hTERT antigen and efficiently stimulate hTERT-specific CTLs from human peripheral blood T lymphocytes and suggest that sufficient expansion could be achieved to be clinically useful for adoptive cell therapy.

publication date

  • June 15, 2005

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-04-2991

PubMed ID

  • 15958591

Additional Document Info

start page

  • 5417

end page

  • 27

volume

  • 65

number

  • 12