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 a chain variable domain sequence fused to the N terminus of an amino acid sequence corresponding to a TCR a chain constant domain extracellular sequence, a second segment constituted by an amino acid sequence corresponding to a TCR ss chain variable domain fused to the N terminus of an amino acid sequence corresponding to TCR ss 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 ass 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 such that the variable domain sequences of the first and second segments are mutually orientated substantially as in native ass T cell receptors.