Adoptive Transfer of CTL

CD8+ T-cell clones specific for MART1MelanA or gp100 were administered to 10 stage IV melanoma patients by Yee and colleagues.125 Adoptively transferred T-cell clones persisted in vivo in response to low-dose IL-2 treatment, trafficked to tumor sites, and eliminated antigen-positive tumor cells. Mixed response or stable disease was observed in 8 of 10 patients for up to 21 months.

Selected peptide-specific, tumor-reactive CD8+ T-cell clones derived from tumor-infiltrating lymphocytes were administered intravenously to 12 patients with stage IV melanoma after a nonmyeloablative conditioning regimen, followed by differing doses of IL-2.126 Although no objective responses were seen, the same authors then administered oligoclonal populations of mixed CD4 and CD8 T cells to 13 patients after treatment with the same nonmyeloablative chemotherapy regimen.127 Persistence of the transferred T cells for up to 7 months occurred and was associated with their proliferation in vivo and trafficking to tumor sites. Seven PR or CR were observed, with 3 patients having SD. Autoimmune vitiligo was associated with response. Ten HLA-A2+ patients with tyrosinase-positive melanomas received intravenous infusions of tyrosinase 369 < n.377 peptide-primed CTL on day 1 and 5 days later for four cycles.128 Two patients experienced disease regression, but CTL were undetectable in the circulation within 5 minutes after injection. The T cells concentrated in the liver and the spleen but did not especially target tumor tissues.

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