ADOPTIVE TRANSFER OF IN VITRO-TARGETED, ACTIVATED T-LYMPHOCYTES RESULTS IN TOTAL TUMOR-REGRESSION

Adoptive immunotherapy of cancer uses the transfer of tumor-reactive i mmune cells, The success of this procedure is dependent upon the speci ficity of the transferred immune cells, their number, and their abilit y to reach their target cells, We genetically modified T lymphocytes a nd equipped them with the ability to specifically recognize tumor cell s. Tumor cells overexpressing the ErbB-2 receptor served as a model. T he target cell recognition specificity is conferred to T lymphocytes b y transduction of a chimeric gene encoding the zeta-chain of the TCR a nd a single chain antibody (scFv(FRP5)) directed against the human Erb B-2 receptor, The chimeric scFv(FRP5)-zeta gene was introduced into pr imary mouse T lymphocytes via retroviral gene transfer, Naive T lympho cytes were activated and infected by cocultivation with a retrovirus-p roducing packaging cell line, The scFv(FRP5)-zeta fusion gene was expr essed in >75% of the T cells, These T cells lysed ErbB-2-expressing ta rget cells in vitro with high specificity. We tested the antitumor eff icacy of scFv(FRP5)-zeta-expressing T cells in a syngeneic BALB/c mode l, The mice were treated with autologous, transduced T cells, The adop tively transferred scFv(FRP5)-zeta-expressing T cells caused total reg ression of ErbB-2-expressing tumors, The presence of the transduced T lymphocytes in the tumor tissue was monitored, No humoral response dir ected against the transduced T cells was observed. Abs directed agains t the ErbB-2 receptor were detected upon tumor lysis.