Allogeneic Anti-EGFR CAR/HLA-A*02-gated Inhibitory Receptor-expressing T-lymphocytes A2B395
allogeneic anti-egfr car/hla-a*02-gated inhibitory receptor-expressing t-lymphocytes a2b395
A preparation of allogeneic T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for the epidermal growth factor receptor (EGFR; HER1; ErbB1), and a leukocyte immunoglobulin-like receptor 1 (LIR-1)-based inhibitory receptor specific for human leukocyte antigen (HLA)-A*02 (HLA-A*02), with potential immunomodulating and antineoplastic activities. Upon administration, the allogeneic anti-EGFR CAR/HLA-A*02-gated inhibitory receptor-expressing T-lymphocytes A2B395 target and bind to EGFR-expressing tumor cells, thereby killing EGFR-expressing tumor cells that have loss of heterozygosity (LOH) for HLA-A*02 protein. The inhibitory receptor specific for HLA-A*02 acts as a self-regulated safety switch that blocks the killing of HLA-A*02-positive EGFR-expressing normal, healthy cells. This may also protect the normal, healthy cells from graft versus host disease (GvHD) resulting from the administration of the allogeneic T-cells. HLA-A*02 is expressed on normal cells but not on tumor cells due to LOH. EGFR, overexpressed by a variety of cancers, plays a key role in tumor cell proliferation and survival.