TARGETING OF T-LYMPHOCYTES TO NEU HER2-EXPRESSING CELLS USING CHIMERIC SINGLE-CHAIN FV RECEPTORS/

Cell surface molecules essential for the transformed phenotype or grow th of malignant cells are attractive targets for anticancer immunother apy. Antibodies specific to Neu/HER2, a human adenocarcinoma-associate d growth factor receptor, were demonstrated to have tumor-inhibitory c apacity. Yet, the inefficient accessibility of antibodies to solid tum ors limits their clinical use. To redirect effector lymphocytes to ade nocarcinomas, we constructed and functionally expressed in T cells chi meric single chain receptor genes incorporating both the Ag-binding do main of anti-Neu/HER2 antibodies and the zeta-signal-transducing subun it of the TCR/CD3 complex or the gamma-signal-transducing subunit of t he Ig Fc receptor complex. Surface expression of the anti-Neu/HER2 chi meric genes in cytotoxic T cell hybridomas endowed them with specific Neu/HER2 recognition enabling their activation for IL-2 production and lysis of transformed cells overexpressing Neu/HER2. These chimeric ge nes hold promise for the immunotherapy of cancer.