iC9-CAR.B7-H3 T cells

Overview

iC9-CAR.B7-H3 T cells are autologous chimeric antigen receptor (CAR) T cells engineered to target B7-H3 (CD276), a checkpoint ligand overexpressed across many solid tumors, and to include an inducible caspase‑9 (iC9) “suicide switch” intended to allow rapid ablation of the cells if serious toxicity occurs. Early-phase, single‑center trials are recruiting in triple‑negative breast cancer (TNBC; NCT06347068) and pancreatic ductal adenocarcinoma (PDAC; NCT06158139). As of October 7, 2025, no human efficacy or safety results for this specific iC9‑CAR.B7‑H3 product have been reported. (aacrjournals.org)

Mechanism of action

• Target: B7‑H3 (CD276), which shows frequent, often high expression in diverse solid tumors (including pancreatic and breast cancers) with relatively limited expression in normal tissues. High B7‑H3 expression has been documented in pan‑cancer profiling and associated with immunosuppressive tumor microenvironments. (aacrjournals.org)
• CAR T construct: Patient T cells are modified to express a B7‑H3–specific CAR to mediate tumor cell recognition and cytotoxicity. Preclinical B7‑H3 CARs that also embed an inducible caspase‑9 safety gene have shown potent activity in vitro and in vivo models. (aacrjournals.org)
• iC9 safety switch: The iC9 system fuses human caspase‑9 to a modified FKBP domain; the small‑molecule dimerizer rimiducid (AP1903) triggers iC9 dimerization and rapid apoptosis of transduced cells. Clinical studies in other T‑cell products demonstrate that rimiducid can eliminate >90% of iC9‑modified T cells within minutes to hours, abrogating toxicities such as GVHD; case reports/series in iC9‑CAR19 suggest mitigation of severe CAR‑T toxicities. (nejm.org)

Clinical development (ongoing trials)

• TNBC (NCT06347068; UNC Lineberger): Phase 1, open‑label, single‑arm, dose‑escalation study of iC9‑CAR.B7‑H3 with cyclophosphamide/fludarabine lymphodepletion; study start June 27, 2024; primary completion estimated May 2026; total planned enrollment ~42. (ichgcp.net)
• PDAC (NCT06158139; UNC Lineberger): Phase 1, open‑label, single‑arm, dose‑escalation; starting dose reported as 1×10^6 transduced cells/kg; study start July 18, 2024; primary completion estimated 2026; planned enrollment ~27. (ichgcp.net)

Related scientific/preclinical support for B7‑H3 targeting includes uveal melanoma models showing eradication of liver metastases with a B7‑H3 CAR carrying an iC9 gene, and PDAC preclinical work presented at AACR 2024 demonstrating elimination of local/distant metastases in a mouse model using iC9.B7‑H3 CAR T cells. (aacrjournals.org)

Efficacy

• No human efficacy data for iC9‑CAR.B7‑H3 T cells have been reported as of October 7, 2025. Trials in TNBC and PDAC are ongoing and have not posted results. (ichgcp.net)

Note: Separate, non‑iC9 B7‑H3 CAR‑T programs (e.g., intracerebroventricular B7‑H3 CAR‑T in DIPG) have reported phase 1 outcomes, but those results do not pertain to the iC9‑CAR.B7‑H3 construct summarized here. (pubmed.ncbi.nlm.nih.gov)

Safety

• No human safety readouts specific to iC9‑CAR.B7‑H3 have been reported to date. (ichgcp.net)
• Rationale for safety feature: The iC9/rimiducid system has clinical precedent in other settings; administration of rimiducid rapidly depletes iC9‑modified T cells and has been used to mitigate severe toxicities from gene‑modified T‑cell therapies, supporting the incorporation of iC9 as a risk‑mitigation tool in new CAR‑T constructs. (nejm.org)

Further reading

• Trial listings and centers
• UNC Lineberger cellular immunotherapy trials overview (includes NCT06347068). (unclineberger.org)
• TNBC phase 1 trial: Study of Autologous CAR‑T Cells Targeting B7‑H3 in TNBC (NCT06347068). (ichgcp.net)
• PDAC phase 1 trial: iC9‑CAR.B7‑H3 T cells in PDAC (NCT06158139). (ichgcp.net)
• Mechanism/target background
• NEJM: Inducible apoptosis (iC9) as a safety switch for adoptive cell therapy. (nejm.org)
• Pan‑cancer analyses of B7‑H3 expression and biology. (aacrjournals.org)
• Preclinical data with iC9‑B7‑H3 CARs
• Clinical Cancer Research: iC9‑B7‑H3 CAR T eradicates uveal melanoma liver metastases (preclinical). (aacrjournals.org)
• AACR 2024 abstract: Adjuvant iC9.B7‑H3 CAR‑T eradicates PDAC metastases in murine model. (aacrjournals.org)

If additional details (dose levels, manufacturing notes, interim safety) are posted by the investigators, results would typically appear in ClinicalTrials.gov updates or peer‑reviewed conference abstracts/manuscripts. (ichgcp.net)

Last updated: Oct 2025