Ex vivo expansion of polyclonal and antigen-specific cytotoxic T lymphocytes by artificial APCs expressing ligands for the T-cell receptor, CD28 and 4-1BB
Marcela V. Maus1, Anna K. Thomas1, Debra G.B. Leonard2, 3, David Allman1, 2, Kathakali Addya3, Katia Schlienger1, James L. Riley1, 2
& Carl H. June1, 2
1
Abramson Family Cancer Research Institute at the University of Pennsylvania Cancer Center, Philadelphia, PA 19104.
2
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104.
3
Molecular Diagnostic Core, University of Pennsylvania, Philadelphia, PA 19104.
The ex vivo priming and expansion of human cytotoxic T lymphocytes (CTLs) has potential for use in immunotherapy applications for cancer and infectious diseases. To overcome the difficulty in obtaining sufficient numbers of CTLs, we have developed artificial antigen-presenting cells (aAPCs) expressing ligands for the T-cell receptor (TCR) and the CD28 and 4-1BB co-stimulatory surface molecules. These aAPCs reproducibly activate and rapidly expand polyclonal or antigen-specific CD8+ T cells. The starting repertoire of CD8+ T cells was preserved during culture. Furthermore, apoptosis of cultured CD8+ T cells was diminished by this approach. This approach may have important therapeutic implications for adoptive immunotherapy.
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