A bispecific single-chain antibody directed against EpCAM/CD3 in combination with the cytokines interferon α and interleukin-2 efficiently retargets T and CD3+CD56+ natural-killer-like T lymphocytes to EpCAM-expressing tumor cells

摘要: Cytokine-induced killer cells (CIK), generated in vitro from peripheral blood mononuclear (PBMC) by addition of interferon γ (IFNγ), interleukin-2 (IL-2), IL-1 and a monoclonal antibody (mAb) against CD3, are highly efficient cytotoxic effector with the CD3+CD56+ phenotype. In this study, we evaluated whether cytotoxicity these natural-killer-like T lymphocytes colorectal tumor cell line HT29 can be enhanced bispecific single-chain (bsAb) directed EpCAM/CD3. For determination bsAb-redirected cellular used new flow-cytometric assay, which directly counts viable assess long-term cytotoxicity. We found that bsAb induced distinct at concentration above 100 ng/ml both PBMC CIK an effector-to-target ratio as low 1:1. revealed higher than PBMC. Cellular appeared after 24 h whereas showed highest 72 h. The cytokines IL-2 IFNα but not granulocyte/macrophage-colony-stimulating factor CIK. When was combined murine mAb BR55-2, recognizes Lewisy antigen, partly augmented, 17-1A, binds to EpCAM well, slightly suppressed bsAb. conclude or vivo EpCAM/CD3 cytokine should for treatment EpCAM-expressing tumors.