iC9-GD2.CAR.IL-15 T-cells

Overview

iC9-GD2.CAR.IL-15 T-cells (also reported as GD2.CAR.15-Ts or IC9-GD2-CD28-OX40 in related programs) are autologous, GD2-targeted CAR T cells “armored” to constitutively express interleukin‑15 (IL‑15) and equipped with an inducible caspase‑9 (iC9) suicide switch. This program is in early clinical testing for GD2‑positive solid tumors, including relapsed/refractory neuroblastoma or osteosarcoma (NCT03721068) and platinum‑refractory lung cancers (NCT05620342). As of the latest registry updates in March–April 2025, no human efficacy or safety outcomes have been posted for these IL‑15–expressing GD2 CAR T cells. (cdek.pharmacy.purdue.edu)

Mechanism of action

• Target: Disialoganglioside GD2, overexpressed on neuroblastoma and other neuroectodermal tumors and variably on some sarcomas and lung cancers. CAR binding redirects T cells to recognize and kill GD2‑expressing tumor cells. (mycancergenome.org)
• IL‑15 “armoring”: Transgenic IL‑15 enhances CAR‑T expansion, persistence, and resistance to exhaustion; in preclinical neuroblastoma models, GD2.CAR.15 T cells showed superior antitumor activity vs. the same CAR without IL‑15. (pubmed.ncbi.nlm.nih.gov)
• Safety switch: The iC9 system allows rapid elimination of infused cells upon administration of a dimerizer drug to mitigate severe toxicities. (pubmed.ncbi.nlm.nih.gov)
• Costimulation: Constructs in this family have used CD28 alone (second‑generation) or CD28 plus OX40 (third‑generation) designs; preclinical work comparing GD2 CAR backbones also supports the inclusion of iC9 and shows culture with IL‑7/IL‑15 can further optimize function. Specific domain usage may differ by study. (pubmed.ncbi.nlm.nih.gov)

Clinical development

• Relapsed/refractory neuroblastoma or osteosarcoma (Phase 1, single‑arm, dose escalation): iC9.GD2.CAR.IL‑15 with cyclophosphamide/fludarabine lymphodepletion; doses 0.25–1.5×10^6 CAR+ cells/kg; primary completion now estimated May 2025; results not yet posted. (NCT03721068; UNC Lineberger). (cdek.pharmacy.purdue.edu)
• Lung cancers (Early Phase 1, single‑arm): Autologous iC9‑GD2.CAR.IL‑15 for extensive‑stage SCLC or stage IV NSCLC after platinum and PD‑(L)1 therapy; recruiting; no results posted. (NCT05620342; UNC Lineberger). (ichgcp.net)

Note: Other GD2‑directed CAR‑T products without IL‑15 (some also using an iC9 safety switch) have reported activity in high‑risk neuroblastoma (e.g., GD2‑CART01, ORR 63% in a Phase 1/2 study), but these data are from different constructs and should not be extrapolated to IL‑15–armored products. (nejm.org)

Efficacy

• No human efficacy outcomes for iC9‑GD2.CAR.IL‑15 have been reported as of March–April 2025 in registered trials. Preclinical neuroblastoma models demonstrate enhanced tumor control with the IL‑15–armored GD2 CAR vs. non‑IL‑15 counterparts. (cdek.pharmacy.purdue.edu)

Safety

• No trial results are posted yet for iC9‑GD2.CAR.IL‑15. The platform includes the iC9 suicide switch intended to abrogate severe toxicities on demand; this approach has been clinically validated in other CAR‑T settings and GD2 CARs without IL‑15. (pubmed.ncbi.nlm.nih.gov)

Further reading

• Phase 1 neuroblastoma/osteosarcoma trial record (NCT03721068). (cdek.pharmacy.purdue.edu)
• Early Phase 1 lung cancer trial record (NCT05620342). (cdek.pharmacy.purdue.edu)
• Preclinical study: Eradication of neuroblastoma by GD2.CAR.IL‑15 T cells; inclusion of iC9 enables on‑demand elimination. (pubmed.ncbi.nlm.nih.gov)
• Preclinical comparison of GD2 CAR costimulatory domains; inclusion of iC9 and synergy with IL‑7/IL‑15 culture. (tandfonline.com)
• Clinical context (different construct): GD2‑CART01 in high‑risk neuroblastoma (NEJM 2024). (nejm.org)

If additional peer‑reviewed human data specific to iC9‑GD2.CAR.IL‑15 are published, those results should supersede the preclinical findings summarized here.

Last updated: Oct 2025