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• W2117994574 abstract "Abstract T-cell adoptive immunotherapy for stringent murine tumor models, such as intracranial, s.c., or advanced pulmonary metastases, routinely uses lymphodepletive conditioning regimens before T-cell transfer, like recent clinical protocols. In this study, we examined whether host lymphodepletion is an obligatory component of curative T-cell therapy; we also examined the mechanism by which it augments therapy. Mice bearing intracranial, s.c., or 10-day pulmonary metastases of MCA 205 received total body irradiation conditioning or were nonirradiated before i.v. transfer of tumor-reactive T cells. Total body irradiation was not required for immunologically specific curative therapy and induction of memory provided that a 3- to 12-fold higher T-cell dose was administered. The mechanism involved enhanced intratumoral proliferation of T-effector cells in total body irradiation–conditioned recipients. In this tumor model, intratumoral Treg cells were not detected; consequently, intratumoral T-effector cells produced identical amounts of IFN-γ upon ex vivo antigen stimulation irrespective of total body irradiation conditioning. Thus, host lymphodepletion augments T-cell immunotherapy through enhanced antigen-driven proliferation of T-effector cells, but curative therapy can be achieved in nonconditioned hosts by escalation of T-cell dose. These data provide a rationale for dose escalation of T-effector cells in situations where single or repeated lymphodepletion regimens are contraindicated." @default.
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• W2117994574 date "2005-10-15" @default.
• W2117994574 modified "2023-10-16" @default.
• W2117994574 title "Host Lymphodepletion Augments T Cell Adoptive Immunotherapy through Enhanced Intratumoral Proliferation of Effector Cells" @default.
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• W2117994574 doi "https://doi.org/10.1158/0008-5472.can-05-1175" @default.
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