A Ror1 Bispecific T Cell Engager For The Treatment Of Chronic Lymphocytic Leukaemia Demonstrates Enhanced Function Following Ibrutinib Treatment

ROR1 is expressed on a range of solid and haematological malignancies, including chronic lymphocytic leukaemia, mantle cell lymphoma and a subset of acute lymphoblastic lymphoma, making it an attractive therapeutic target. In keeping with this, ROR1 CAR T cells and a ROR1 antibody, are being investigated as novel treatments [NCT02222688, NCT02776917 & NCT02706392]. BiTEs are small, 55kDa antibody based therapeutics composed of two single chain variable fragments (scFv) linked in tandem by a flexible linker. One scFv binds to tumour antigens and the other to the CD3 complex, bringing target cells and T cells in close proximity, facilitating formation of cytotoxic synapses and resulting in target cell death. We have generated a fully humanised ROR1 BiTE which unlike conventional antibodies recruits and utilises the inherent cytotoxic potential of polyclonal resident T cells and does not require ex vivo cell manipulation. We therefore investigated the potential of a ROR1 BiTE for the treatment of CLL.