Targeting of T cells to CEA-expressing tumor cells by chimeric immune receptors with a highly specific single-chain anti-CEA activity

Abstract

Background: Lymphokine-activated killer (LAK) cell therapy or cytokine gene therapy is a potential new modality in the treatment of cancer. However, one limitation in the use of adoptive cellular immunotherapy for cancer lies in the difficulty in obtaining tumor-specific effector cells which can efficiently reach their target cells.

Materials and methods: To effectively target T cells to carcinoembryonic antigen (CEA)-positive tumor cells, we constructed a chimeric immune receptor (CIR) gene which encoded a highly specific anti-CEA scFv antibody, the human CD8 alpha hinge region, the CD28 transmembrane and cytoplasmic domains, and the human CD3 zeta-chain. The resulting CIR gene, termed F39scFv/CIR-2, was transfected into human T cells.

Results: The cell surface expression of the F39scFv/CIR-2 receptors in T cells was demonstrated by flow cytometry. When incubated with CEA-positive tumor cells, the transfected T cells formed rosette-like aggregates around the tumor cells, thus indicating the cell-specific targeting of T cells.

Conclusion: This strategy may allow the development of new approaches for the adoptive immunotherapy of CEA-positive tumors in humans, especially in combination with LAK cell therapy or cytokine gene therapy.