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

Functional impairment of human T-lymphocytes following PHA-induced expansion and retroviral transduction: implications for gene therapy

“…Our findings concur with those of recent studies showing that T cells costimulated with anti-CD3/anti-CD28 can retain normal function. 15,29 They also suggest that even for iCD3/iCD28 costimulation, the intensity and duration of expansion need to be optimized to preserve the function.…”

Expression and function of 4‐1BB during CD4 versus CD8 T cell responses in vivo

“…Extensive evidence supports the role of 4-1BB as a costimulatory molecule that can function independently of CD28 [9,13,14] to activate T cells [10,15,16]. 4-1BB can influence cytokine production, proliferation and survival of T cells in vitro and in vivo [8][9][10][16][17][18][19][20][21][22][23][24]. Stimulatory anti-4-1BB antibodies show a preferential role for 4-1BB in CD8 + T cell activation in vitro [20].…”

Establishment and Characterization of a Cell Based Artificial Antigen-Presenting Cell for Expansion and Activation of CD8+ T Cells Ex Vivo

“…Artificial antigen-presenting systems encompass both cell-based and acellular technologies. Several diverse scaffoldding systems such as genetically engineered insect cells, mouse fibroblasts, human tumor cell lines (3,4,(11)(12)(13), microbeads, artificial liposomes, and biomembrane derivatives (exosomes, immunosomes) (14, 15) have been developed. However, the self-limitation of insect cells at 37 o C (the viable temperature for D. melanogaster cells is 27 o C) could lead to massive release of D. melanogaster antigens and limit the duration of the contact between the T cell and the aAPC (16,17).…”

“…After K32 cells are coated with anti-CD3 and anti-CD28 mouse IgG monoclonal antibodies (K32/CD3/28), they could stimulate the expansion of polyclonal CD4 + T lymphocytes, but not CD8 + T cells. When the K32 cells were transfected with 4-1BBL which can preferentially activate CD8 + T cells, CD8 + T cells showed long-term expansion and survival (3). In addition, K32 cells also show constitutive expression of B7-H3, ICAM-1, and LFA-3 (3,4), all of which are ligands for costimulatory receptors other than CD28.…”