CD40-activated human B cells: an alternative source of highly efficient antigen presenting cells to generate autologous antigen-specific T cells for adoptive immunotherapy

• Published in: The Journal of clinical investigation 1997-12, Vol.100 (11), p.2757-2765
• Main Authors: Schultze, J L, Michalak, S, Seamon, M J, Dranoff, G, Jung, K, Daley, J, Delgado, J C, Gribben, J G, Nadler, L M
• Format: Article
• Language: English
• Subjects: 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 - secretion; 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
• ISSN: 0021-9738
• DOI: 10.1172/JCI119822

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.