Recruiting cytotoxic T cells to folate-receptor-positive cancer cells.

Herein, we describe the synthesis of a chemically defined anti-CD3 Fab-folate conjugate that targets cytotoxic T cells to folate receptor positive (FR) tumors. The unnatural amino acid pacetylphenylalanine (pAcPhe) was site-specifically incorporated into an anti-CD3 Fab and conjugated to folate via the formation of a stable oxime linkage. The anti-CD3 Fab-folate conjugate was able to promote T cell mediated killing of FR cancer cells in culture. Moreover, the anti-CD3 Fab-folate conjugate potently eliminates tumor xenografts in mice. This approach can likely be generalized to other ligands that bind cancer and other pathogenic cells.