Ex vivo induction and expansion of antigen-specific cytotoxic T cells by HLA-Ig-coated artificial antigen-presenting cells

Nat Med. 2003 May;9(5):619-24. doi: 10.1038/nm869. Epub 2003 Apr 21.


Adoptive immunotherapy holds promise as a treatment for cancer and infectious diseases, but its development has been impeded by the lack of reproducible methods for generating therapeutic numbers of antigen-specific CD8(+) cytotoxic T lymphocytes (CTLs). As a result, there are only limited reports of expansion of antigen-specific CTLs to the levels required for clinical therapy. To address this issue, artificial antigen-presenting cells (aAPCs) were made by coupling a soluble human leukocyte antigen-immunoglobulin fusion protein (HLA-Ig) and CD28-specific antibody to beads. HLA-Ig-based aAPCs were used to induce and expand CTLs specific for cytomegalovirus (CMV) or melanoma. aAPC-induced cultures showed robust antigen-specific CTL expansion over successive rounds of stimulation, resulting in the generation of clinically relevant antigen-specific CTLs that recognized endogenous antigen-major histocompatibility complex complexes presented on melanoma cells. These studies show the value of HLA-Ig-based aAPCs for reproducible expansion of disease-specific CTLs for clinical approaches to adoptive immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigen Presentation
  • Antigen-Presenting Cells / physiology*
  • Antigens, Neoplasm
  • Cytomegalovirus / immunology
  • HLA Antigens / immunology*
  • Humans
  • Immunoglobulins / immunology*
  • Immunotherapy, Adoptive
  • MART-1 Antigen
  • Neoplasm Proteins / immunology
  • T-Lymphocytes, Cytotoxic / physiology*
  • Tumor Cells, Cultured


  • Antigens, Neoplasm
  • HLA Antigens
  • Immunoglobulins
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins