Eradication of established tumors by CD8(+) T cell adoptive immunotherapy

We generated the DUC18 T cell receptor transgenic mouse expressing an H-2K( d)-restricted transgenic T cell receptor specific for the syngeneic CMS5 fi brosarcoma rejection antigen mutated ERK2(136-144). DUC18 mice were capable of specifically eliminating lethal CMS5 tumor challenges, and transfer of DUC18 splenocytes to naive nontransgenic recipients conferred protection fr om subsequent and established CMS5 tumor burdens. Eradication of establishe d tumor burdens by adoptive transfer of DUC18 splenocytes was dose and time dependent. Transferred tumor-specific T cells remained functional in vivo and capable of rejecting small tumors even in the presence of large, establ ished tumor burdens. These findings highlight the kinetic battle between tu mor growth and the production of a tumor-specific response and have critica l implications for effective adoptive immunotherapy.