Allogeneic TCRa/b-depleted HA-1 Minor Histocompatibility Antigen-Reactive TCR-Modified RQR8-expressing T Cells BSB-1001
allogeneic tcra/b-depleted ha-1 minor histocompatibility antigen-reactive tcr-modified rqr8-expressing t cells bsb-1001
A preparation of T-cell receptor (TCR) alpha and beta (TCRa/b)-depleted donor-derived T-lymphocytes that have been transduced with a lentivirus vector encoding a TCR specific for HLA-A*02:01-restricted minor histocompatibility antigen HA-1 (HA1) and expressing RQR8, with potential immunomodulating and antineoplastic activities. Following HLA-matched allogeneic hematopoietic cell transplantation (HCT) in HLA-A*02:01 positive patients, allogeneic TCRa/b-depleted HA-1 minor histocompatibility antigen-reactive TCR-modified RQR8-expressing T cells BSB-1001 specifically recognize and bind to HA-1 expressed on tumor cells. This may lead to cytotoxic T-lymphocyte (CTL)-mediated elimination of tumor cells expressing HLA-A*02:01 HA-1. HA-1 is a lineage-specific antigen found on leukemia cells. BSB-1001 carries the universal RQR8 safety "off" switch, which allows selective removal of the T-cells through both complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) following administration of rituximab if unacceptable side-effects occur. CRISPR-cas9 editing of the donor T-cells deletes the endogenous TCRa/b chains. Depletion of TCRa/b increases expression of the transduced TCR and reduces risk of graft-versus-host disease (GVHD) caused by native TCRs.