autologous CD38-4SCAR-expressing T cells 4SCAR38
A preparation of genetically modified autologous T cells transduced with a replication incompetent, self-inactivating lentiviral vector expressing a fourth generation chimeric antigen receptor (4SCAR) consisting of an anti-CD38 single chain variable fragment (scFv) that is coupled to the costimulatory signaling domains CD28, CD137, CD27 and the zeta chain of the T-cell receptor (TCR), and is fused with the suicide gene inducible caspase 9 (iCasp9), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, autologous CD38-4SCAR-expressing T cells 4SCAR38 are directed to and induce selective toxicity in CD38-expressing tumor cells. iCasp9 consists of a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V) linked to human caspase 9. If the administered T cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered. AP1903 binds to the drug binding FKBP12-F36V domain and induces activation of caspase 9, which results in the apoptosis of the administered T cells and enhances safety of this agent. CD38, a type II transmembrane glycoprotein, is present on various immune cells and hematologic malignancies, and its expression has been correlated with poor prognosis. CD28, CD137 and CD27, T-cell surface-associated co-stimulatory molecules, are required for full T-cell activation and enhance both proliferation of T cells and antitumor activity.
Synonym: | 4S-CD38-CAR-T cell 4SCAR38 T cells anti-CD38 CAR-T cells 4SCAR38 anti-CD38-CD28-CD137-CD27-CD3z-iCasp9 CAR T cells 4SCAR38 CD38-4SCAR-expressing T lymphocytes CD38-scFv/CD28/CD137/CD27/CD3z-iCasp9 T cells CD38-specific 4th generation chimeric antigen receptor-modified T cells |
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Code name: | 4SCAR38 |