Preferred Label : Autologous Anti-PSMA CAR/CD2/dnTGF-BRII/PD-1:CD28 Switch Receptor-expressing T-cells
TmPSMA-02;
NCIt synonyms : Autologous Anti-PSMA CAR-T Cells TmPSMA-02; Autologous Anti-PSMA CAR/CD2/dnTGFBR2/PD-1:CD28 Switch Receptor-expressing T Cells
TmPSMA-02;
NCIt definition : A preparation of autologous T-lymphocytes that have been genetically modified and
transduced with a lentiviral vector to express a chimeric antigen receptor (CAR) consisting
of an anti-prostate specific membrane antigen (PSMA) single chain variable fragment
(scFv) and the co-stimulatory domain CD2, a dominant negative (dn) form of transforming
growth factor-beta (TGF-beta; TGFb) receptor (dnTGF-BRII), and a PD-1:CD28 switch
receptor composed of the extracellular ligand binding domain of the human inhibitory
receptor programmed cell death protein 1 (PD-1; PDCD1) fused to the transmembrane
and cytoplasmic co-stimulatory signaling domains of CD28, with potential immunomodulating
and antineoplastic activities. Upon reintroduction into the patient, autologous anti-PSMA
CAR/CD2/dnTGF-BRII/PD-1:CD28 switch receptor-expressing T-cells TmPSMA-02 are directed
to and induce selective toxicity in PSMA-expressing tumor cells. PSMA, a tumor-associated
antigen (TAA) and type II transmembrane protein, is expressed on the membrane of prostatic
epithelial cells and overexpressed on prostate tumor cells as well as a variety of
other solid tumors. The inclusion of dnTGF-BRII blocks the signaling of the immunosuppressive
cytokine TGFb in the tumor microenvironment (TME) and makes the TmPSMA-02 T-cells
resistant to TGFb. TGFb negatively regulates T-cell proliferation and activation and
plays a key role in tumor immune suppression. The PD-1:CD28 switch receptor expressed
by the TmPSMA-02 T-cells targets and binds to the PD-1 ligands, programmed cell death
ligand 1 (PD-L1) and 2 (PD-L2), expressed on tumor cells. The nature of the PD-1/CD28
switch receptor fusion protein prevents the normal PD1/PD-L1-mediated T-cell suppression
and, instead, promotes signaling through the CD28 domain, which results in the stimulation
of T-lymphocytes. This induces enhanced toxicity against tumor cells.;
Molecule name : TmPSMA 02; TmPSMA-02;
NCI Metathesaurus CUI : CL1798779;
Origin ID : C190115;
UMLS CUI : C5783503;
Semantic type(s)
- Cell [UMLS semantic type]
- chemical_or_drug_affects_cell_type_or_tissue
- chemical_or_drug_has_mechanism_of_action
- chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
- has_target
