autologous anti-ROR1 CAR-mbIL15-safety switch/intrinsic PD-1 blockade T cells PRGN-3007

A preparation of autologous T lymphocytes engineered to express, using a single non-viral multicistronic transposon plasmid, a chimeric antigen receptor (CAR) targeting the receptor tyrosine kinase-like orphan receptor 1 (ROR1), membrane-bound IL-15 (mbIL15), a kill switch and an intrinsic programmed death 1 (PD-1; PDCD1; CD279; programmed cell death-1) checkpoint blockade, with potential immunomodulatory and antineoplastic activities. After isolation, non-viral gene transfer, and expansion in culture, the autologous anti-ROR1 CAR-mbIL15-safety switch/intrinsic PD-1 blockade T cells PRGN-3007 are reintroduced into the patient and are directed to tumor cells expressing ROR1, which may result in a selective toxicity against, and lysis of ROR1-expressing tumor cells. ROR1 is expressed during embryogenesis and upregulated in certain tumor types with minimal expression in healthy adult tissues. High levels of ROR1 expression often correlate with poor prognosis. PD-1, an immune checkpoint receptor expressed on T cells, plays a key role in tumor immune evasion by binding to its ligand programmed death ligand 1 (PD-L1; cluster of differentiation 274; CD274; programmed cell death-1 ligand 1) expressed on tumor cells. By removing PD-1 from T cells, PD-1-mediated signaling is halted which may decrease T-cell exhaustion and may enhance T-cell activity against ROR1-expressing tumor cells. mbIL15 enhances T-cell expansion and persistence through sustained IL-15 signaling. The kill switch allows for improved safety as it can promote selective elimination of the CAR-T cells upon treatment with the kill switch activator antibody.