T-CELL RECEPTORS CONTAINING A NON-NATIVE DISULFIDE INTERCHAIN BOND LINKED TO THERAPEUTIC AGENTS.

摘要

The present invention provides a dimeric TCR (dTCR) or single-chain TCR (scTCR) associated with selected therapeutic agents, wherein said TCR comprises a first segment constituted by an amino acid sequence corresponding to a TCR chain variable domain sequence fused to the N terminus of an amino acid sequence corresponding to a TCR chain constant domain extracellular sequence, a second segment constituted by an amino acid sequence corresponding to a TCR a chain variable domain fused to the N terminus of an amino acid sequence corresponding to TCR a chain constant domain extracellular sequence, a disulfide bond between the first and second chains, said disulfide bond being one which has no equivalent in native a T cell receptors, and in the case of said scTCRs further comprising a linker sequence linking the C terminus of the first segment to the N terminus of the second segment, or vice versa, the length of the linker sequence and the position of the disulfide bond being suc h that the variable domain sequences of the first and second segments are mutually orientated substantially as in native a T cell receptors.