Autologous IL-15/IL-21-iC9-expressing Anti-glypican-3 CAR T-cells

**Semantic type:** Cell|Pharmacologic Substance

**Definition:** A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for glypican-3 (GPC3) and express the two cytokines interleukin-15 (IL-15) and interleukin-21 (IL-21), and the suicide gene, inducible caspase 9 (iCasp9 or iC9), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, autologous IL-15/IL-21-iC9-expressing anti-glypican-3 CAR T-cells specifically target and bind to GPC3-expressing tumor cells, resulting in tumor cell lysis. GPC3, a heparan sulfate proteoglycan and a member of the glypican family, is overexpressed on certain tumor cell types while minimally expressed on normal, healthy cells. GPC3 plays an important role in cellular proliferation and differentiation. The cytokines IL-15 and IL-21 promote T-cell survival, expansion and persistence, which may potentiate the immune response against tumor cells. The iCasp9 safety switch consists of a full-length caspase 9, including its caspase recruitment domain, linked to a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V). If the administered CAR T-cells lead to unacceptable side effects, the chemical homodimerizer rimiducid (AP1903) can be administered, which binds to the FKBP12-F36V drug-binding domain, activates caspase 9 and results in apoptosis of the administered CAR T-cells.

**Synonyms:** - Autologous Anti-GPC3-CAR-IL-15-IL-21-iC9-expressing T-lymphocytes - Autologous Anti-glypican-3 CAR-IL-15-IL-21-iC9-expressing CAR T-cells - Autologous Anti-glypican-3 CAR-IL-15-IL-21-iCasp9-expressing CAR T-cells - Autologous IL-15/IL-21-armored iC9-expressing Anti-GPC3 CAR T Cells - Autologous IL-15/IL-21-armored iC9-expressing Anti-GPC3 CAR T-cells - Autologous IL-15/IL-21-armored iC9-expressing Anti-GPC3 CAR-T Cells - Autologous IL-15/IL-21-armored iC9-expressing Anti-GPC3 CAR-expressing T-cells - Autologous SC-CAR.GPC3xIL15-IL21-expressing T Cells - IL-15/IL-21-armored iCasp9-expressing Glypican-3-specific CAR-expressing Autologous T-cells