LYSIS OF OVARIAN-CANCER CELLS BY HUMAN-LYMPHOCYTES REDIRECTED WITH A CHIMERIC GENE COMPOSED OF AN ANTIBODY VARIABLE REGION AND THE FC-RECEPTOR GAMMA-CHAIN

To expand the spectrum of recognition of effector lymphocytes and to r edirect them towards predefined targets, we have altered the specifici ty of human tumor-infiltrating lymphocytes (TIL) through stable modifi cation with chimeric receptor genes consisting of single-chain antibod y variable regions linked to the gamma subunit common to the immunoglo bulin (Ig)G and IgE Fc receptors. Using either hapten or ovarian carci noma-specific monoclonal antibodies, we constructed chimeric receptor genes and retrovirally introduced them into CD8+ TIL. Redirected TIL s pecifically lysed trinitrophenyl-labeled Daudi or a human ovarian carc inoma cell line (IGROV-1), and secreted granulocyte/macrophage colony- stimulating factor upon stimulation with the appropriate antigen. This strategy may allow new approaches towards the adoptive immunotherapy of cancer in humans.