Targeting of T lymphocytes to Neu/HER2-expressing cells using chimeric single chain Fv receptors.

I Stancovski, DG Schindler, T Waks… - … (Baltimore, Md.: 1950 …, 1993 - journals.aai.org
I Stancovski, DG Schindler, T Waks, Y Yarden, M Sela, Z Eshhar
Journal of immunology (Baltimore, Md.: 1950), 1993journals.aai.org
Cell surface molecules essential for the transformed phenotype or growth of malignant cells
are attractive targets for anticancer immunotherapy. Antibodies specific to Neu/HER2, a
human adenocarcinoma-associated growth factor receptor, were demonstrated to have
tumor-inhibitory capacity. Yet, the inefficient accessibility of antibodies to solid tumors limits
their clinical use. To redirect effector lymphocytes to adenocarcinomas, we constructed and
functionally expressed in T cells chimeric single chain receptor genes incorporating both the …
Abstract
Cell surface molecules essential for the transformed phenotype or growth of malignant cells are attractive targets for anticancer immunotherapy. Antibodies specific to Neu/HER2, a human adenocarcinoma-associated growth factor receptor, were demonstrated to have tumor-inhibitory capacity. Yet, the inefficient accessibility of antibodies to solid tumors limits their clinical use. To redirect effector lymphocytes to adenocarcinomas, we constructed and functionally expressed in T cells chimeric single chain receptor genes incorporating both the Ag-binding domain of anti-Neu/HER2 antibodies and the zeta-signal-transducing subunit of the TCR/CD3 complex or the gamma-signal-transducing subunit of the Ig Fc receptor complex. Surface expression of the anti-Neu/HER2 chimeric 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 genes hold promise for the immunotherapy of cancer.
journals.aai.org