CD40-activated Human B Cells: An Alternative Source of Highly Efficient Antigen Presenting Cells to Generate Autologous Antigen-Specific T Cells for Adoptive Immunotherapy

J Clin Invest. 1997 Dec 1;100(11):2757-65. doi: 10.1172/JCI119822.

Abstract

Multiple clinical trials have shown the efficacy of adoptively transferred allogeneic antigen-specific T cells for the treatment of viral infections and relapsed hematologic malignancies. In contrast, the therapeutic potential of autologous antigen-specific T cells has yet to be established since it has been technically difficult to generate sufficient numbers of these T cells, ex vivo. A major obstacle to the success of this objective derives from our inability to simply and rapidly isolate and/or expand large numbers of highly efficient antigen presenting cells (APCs) for repetitive stimulations of antigen-specific T cells in vitro. We show that autologous CD40-activated B cells represent a readily available source of highly efficient APC that appear to have several important advantages over other APCs for ex vivo T cell expansion including: (a) methodological simplicity necessary to generate continuously large numbers of APCs from just 50 cm3 of peripheral blood without loss of APC function; (b) capacity to induce high peak T cell proliferation and interferon-gamma production without IL-10 production; (c) ease in cryopreservation; and (d) markedly reduced cost. We, therefore, contend that CD40-activated B cells are an alternative source of highly efficient APCs with which to generate antigen-specific T cells ex vivo for autologous adoptive immunotherapy.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigens, Neoplasm / immunology
  • Antigens, Viral / immunology
  • B-Lymphocytes / immunology*
  • CD40 Antigens / immunology*
  • Cell Division
  • Cells, Cultured
  • Cost-Benefit Analysis
  • Cytotoxicity Tests, Immunologic
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Humans
  • Immunotherapy, Adoptive
  • Influenza A virus / immunology
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / metabolism
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology
  • Mice
  • Monophenol Monooxygenase / immunology
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / immunology
  • T-Lymphocytes / immunology*
  • Time Factors
  • Tumor Cells, Cultured
  • Viral Matrix Proteins / chemical synthesis
  • Viral Matrix Proteins / immunology

Substances

  • Antigens, Neoplasm
  • Antigens, Viral
  • CD40 Antigens
  • Peptide Fragments
  • Viral Matrix Proteins
  • influenza virus membrane protein (58-66)
  • Interleukin-10
  • Interferon-gamma
  • Monophenol Monooxygenase