4.7 Article

A cell-based artificial antigen-presenting cell coated with anti-CD3 and CD28 antibodies enables rapid expansion and long-term growth of CD4 T lymphocytes

Journal

CLINICAL IMMUNOLOGY
Volume 105, Issue 3, Pages 259-272

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/clim.2002.5277

Keywords

ex vivo expansion; adoptive immunotherapy; costimulation; IL-15; PD-L1; PD-L2; B7-H3

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Funding

  1. NIDDK NIH HHS [DK07748] Funding Source: Medline

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We compared the ability of two genetically modified myeloid cells, K562 and U937, to serve as artificial antigen-presenting cells (aAPC). Both aAPC were stably transfected with the low-affinity Fcy receptor CD32 (K32/U32 cells). K32 cells loaded with anti-CD3 and anti-CD28 Ab (K32/CD3/28) induced more rapid CD4 T-ceIl expansion than CD3/28-coated beads. In contrast, U32/CD3/28 induced high levels of CD4 T-cell thymidine uptake but were unable to sustain long-term T-cell expansion. R32 cells, but not U32 cells, loaded with anti-CD3 alone also stimulated CD4 T-cell growth and IL-2 secretion, indicating the expression of additional costimulatory molecules on K32 cells. We found constitutive expression of B7-H3 and a strong upregulation of mRNA encoding for IL-15, PD-L1, and PD-L2 after coculture with CD4 T cells activated by K32/CD3/28 but not U32/CD3/28. We conclude that K32 aAPCs are a robust system for clinical scale ex vivo expansion of CD4 T cells. (C) 2002 Elsevier Science (USA).

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