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

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 in...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 1993-10, Vol.37 (5), p.323-328
Main Authors: FLENS, M. J, MULDER, W. M. C, BRIL, H, VON BLOMBERG VAN DE FLIER, M. B. E, SCHEPER, R. J, VAN LIER, R. A. W
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - pharmacology
Antineoplastic agents
Biological and medical sciences
CD28 Antigens - immunology
CD3 Complex - immunology
Cytotoxicity, Immunologic
Humans
Immunophenotyping
Immunotherapy
Interleukin-2 - pharmacology
Lymphocyte Activation
Lymphocytes, Tumor-Infiltrating - immunology
Medical sciences
Neoplasms - immunology
Original
Pharmacology. Drug treatments
Recombinant Proteins - pharmacology
Tumor Cells, Cultured
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Summary: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.
ISSN:0340-7004
1432-0851
DOI:10.1007/BF01518455