Protein-based T-cell receptor knockdown

A nucleic acid sequence encoding a molecule which disrupts the expression of native T cell-receptor (TCR) on the surface of a T cell, which molecule comprises a binding portion comprising a binding domain which binds to one or more components of the TCR/CD3 complex and which is a UCHT1 antibody or a Jovi.1 antibody or is derived from a UCHT1 antibody or a Jovi.1 antibody, and a retention portion comprising a retention domain that intracellularly retains the one or more components within the endoplasmic reticulum (ER) or Golgi apparatus and which is a KDEL sequence, wherein the retention domain is in frame at the C-terminal to the binding domain, and wherein the binding domain comprises:

• (a) three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) contained within the heavy chain variable region (HCVR) sequence of SEQ ID NO:
• 7, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained within the light chain variable region (LCVR) sequence of SEQ ID NO:
• 8;
• or
• (b) three heavy chain CDRs (HCDR1, HCDR2 and HCDR3) contained within the HCVR sequence of SEQ ID NO:
• 15, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained within the LCVR sequence of SEQ ID NO:
• 16.