Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Butler, M.O. et al.

Butler, Lee, Ansén, Neuberg, Hodi, Murray, Drury, Berezovskaya, Mulligan, Nadler, Hirano,

Long-lived antitumor CD8+ lymphocytes for adoptive therapy generated using an artificial antigen-presenting cell.

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 patient. 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, CD54, CD58, CD80, and the dendritic cell maturation marker CD83. We tested the ability of aAPC to generate tumor antigen-specific CTL under optimal culture conditions. The number, phenotype, effector function, and in vitro longevity of generated CTL were determined. RESULTS: Stimulation of CD8(+) T cells with peptide-pulsed aAPC generated large numbers of functional CTL that recognized a variety of tumor 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 melanoma tumor lines naturally expressing a target melanoma antigen. Furthermore, antitumor CTL were easily generated in all melanoma patients 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.[1]

References

Long-lived antitumor CD8+ lymphocytes for adoptive therapy generated using an artificial antigen-presenting cell. Butler, M.O., Lee, J.S., Ansén, S., Neuberg, D., Hodi, F.S., Murray, A.P., Drury, L., Berezovskaya, A., Mulligan, R.C., Nadler, L.M., Hirano, N. Clin. Cancer Res. (2007) [Pubmed]

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