GROWTH-RETARDATION OF TUMORS BY ADOPTIVE TRANSFER OF CYTOTOXIC T-LYMPHOCYTES REPROGRAMMED BY CD44V6-SPECIFIC SCFV-ZETA-CHIMERA

Variants of the CD44 protein family containing sequences encoded by va riant exon 6 (v6) are involved in the metastatic spread of rat and hum an tumors. The rat-specific antibody 1.1 ASML, which recognizes a v6 e pitope, interferes with metastatic dissemination of a rat pancreatic c arcinoma. The single-chain antigen-binding fragment of this monoclonal antibody was fused to the zeta-chain of the T-cell receptor complex. The appropriate fusion gene was incorporated into a retroviral gene tr ansfer vector. Murine cytotoxic T lymphocytes (CTLs) were infected, an d cellular clones which express the single-chain zeta-chain fusion pro tein on their cell surface were selected. These CTLs are not MHC-restr icted in their CD44v6 recognition and exhibit in vitro lytic activity toward cells expressing CD44 variants comprising exon v6. Tumor cell x enografts grown in athymic nude mice are suppressed in their growth up on infusion of the genetically manipulated CTLs. Our data indicate tha t the CD44v6 epitope is an effective target for immune tumor therapy a nd demonstrate the efficacy of genetically engineered CTLs in targetin g tumors expressing such epitopes. (C) 1996 Wiley-Liss, Inc.