Long-lived antitumor XXXX + lymphocytes for adoptive therapy generated using an artificial antigen-presenting cell.

@entity1 @entity5 @entity7938 @entity8730 @entity7937 @entity2071 @entity405 @entity320
PURPOSE: Antitumor lymphocytes can be generated ex vivo unencumbered by immunoregulation found in vivo. Adoptive transfer of these cells is a promising therapeutic modality that could establish long-term antitumor immunity. However, the widespread use of adoptive therapy has been hampered by the difficulty of consistently generating potent antitumor lymphocytes in a timely manner for every @entity1 . To overcome this, we sought to establish a clinical grade culture system that can reproducibly generate antigen-specific cytotoxic T lymphocytes (CTL). EXPERIMENTAL DESIGN: We created an off-the-shelf, standardized, and renewable artificial antigen-presenting cell (aAPC) line that coexpresses HLA class I, @entity2071 , @entity7937 , @entity7938 , and the dendritic cell maturation marker @entity8730 . We tested the ability of aAPC to generate @entity5 antigen-specific CTL under optimal culture conditions. The number, phenotype, effector function, and in vitro longevity of generated CTL were determined. RESULTS: Stimulation of @entity405 (+) T cells with peptide-pulsed aAPC generated large numbers of functional CTL that recognized a variety of @entity5 antigens. These CTLs, which possess a phenotype consistent with in vivo persistence, survived ex vivo for prolonged periods of time. Clinical grade aAPC(33), produced under current Good Manufacturing Practices guidelines, generated sufficient numbers of CTL within a short period of time. These CTL specifically lysed a variety of @entity320 lines naturally expressing a target @entity320 antigen. Furthermore, antitumor CTL were easily generated in all @entity320 @entity1 examined. CONCLUSIONS: With clinical grade aAPC(33) in hand, we are now poised for clinical translation of ex vivo generated antitumor CTL for adoptive cell transfer.
