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Efficient expansion of tumor-infiltrating lymphocytes from solid tumors by stimulation with combined CD3 and CD28 monoclonal antibodies

  • Original Articles
  • CD3 mAb, CD28 mAb, Expansion, Initiation Phase, Tumor-Infiltrating Lymphocytes
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Combined CD3 and CD28 monoclonal antibodies (mAb) may initiate efficient activation and expansion of tumor-infiltrating lymphocytes (TIL). In this study we compared phenotypical and functional characteristics of TIL from a group of 17 solid human tumors, stimulated either by high-dose recombinant interleukin 2 (rIL-2, 1000 IU/ml) or by a combination of anti-CD3 and anti-CD28 monoclonal antibodies in the presence of low-dose rIL-2 (10 IU/ml). Compared to activation with high-dose rIL-2, stimulation of TIL with CD3/CD28 mAb induced significantly stronger proliferation and yielded higher levels of cell recovery on day 14. Following the CD3/CD28 protocol, expansion of an almost pure population of CD3+ cells was obtained. Whereas CD4+ cells dominated in the first week of culturing, within 4 weeks the CD8+ population increased to over 90%. The specific capacity to kill autologous tumor cells was not increased as compared to the high-dose rIL-2 protocol, but all cultures showed high cytotoxic T cell activity as measured in a CD3-mAb-mediated redirected kill assay. These studies show that combined CD3 and CD28 mAb are superior to rIL-2 with respect to the initiation of expansion of CD8+ cytolytic TIL from solid tumors. Stimulation with specific tumor antigens at a later stage of culturing may further augment the expansion of tumor-specific cytolytic T cells.

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Authors and Affiliations

  1. Department of Clinical Viro-Immunology, Publication Secretariat, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, PO Box 9406, 1006 AK, Amsterdam, The Netherlands

    Marcel J. Flens & René A. W. van Lier

  2. Department of Pathology, Free University Hospital, Amsterdam, The Netherlands

    Wilhelmina M. C. Mulder, Herman Bril, Mary B. E. von Blomberg van de Flier & Rik J. Scheper

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  1. Marcel J. Flens
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  2. Wilhelmina M. C. Mulder
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  3. Herman Bril
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  4. Mary B. E. von Blomberg van de Flier
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  5. Rik J. Scheper
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  6. René A. W. van Lier
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Flens, M.J., Mulder, W.M.C., Bril, H. et al. Efficient expansion of tumor-infiltrating lymphocytes from solid tumors by stimulation with combined CD3 and CD28 monoclonal antibodies. Cancer Immunol Immunother 37, 323–328 (1993). https://doi.org/10.1007/BF01518455

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  • DOI: https://doi.org/10.1007/BF01518455

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