B7-H3 CAR-T

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Also known as:

B7-H3CART B7-H3-CAR T Cells TX103 4SCAR-276 +1 more

Cancer types include:

kidney cancer melanoma ovarian cancer sarcoma

TrialFetch AI Analysis

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Overview

B7-H3 CAR-T therapies are autologous or allogeneic chimeric antigen receptor T cells engineered to recognize B7-H3 (CD276), a checkpoint-like immunomodulatory molecule overexpressed across many solid tumors and associated with poor outcomes. Clinical-stage programs include TX103 for recurrent glioblastoma (rGBM) and a fourth‑generation construct 4SCAR‑276 being studied in B7‑H3–positive solid tumors. Interim human data have been presented for TX103 in rGBM; other programs (e.g., 4SCAR‑276) remain in early-phase evaluation without published response outcomes to date. (aacrjournals.org)

Mechanism of action

Target: B7‑H3 (CD276), a B7 family member variably acting as an immune co‑inhibitory signal; it is highly expressed on many cancers and generally limited on normal tissues. (aacrjournals.org)
Modality: Patient (autologous) or donor-derived (allogeneic) T cells are transduced with a CAR recognizing B7‑H3, redirecting cytotoxicity toward B7‑H3–expressing tumor cells. Some constructs include additional design elements (e.g., fourth‑generation costimulation and an inducible caspase‑9 safety switch in 4SCAR‑276). (trial.medpath.com)

Efficacy

TX103 (autologous B7‑H3 CAR‑T; rGBM) - Study: Phase 1, single‑arm, dose‑escalation with intracavitary and/or intraventricular administration via Ommaya; NCT05241392. Interim ASCO 2024 abstract reported 13 treated patients between March 2022 and January 2024. (ascopubs.org) - Outcomes (interim): Among six patients from dose levels 1–2 evaluable for 12‑month survival as of January 2024, 12‑month OS was 83.3% (95% CI 58.3–100); median OS 20.3 months (95% CI 20.3–not reached). In dose level 2, two of three patients achieved partial and complete responses, respectively. CSF cytokines (e.g., IL‑6, IFN‑γ) and CAR transgene copies increased post‑infusion, with minimal peripheral changes. (ascopubs.org)

Allogeneic B7‑H3 CAR‑T in recurrent high‑grade glioma (for context; different product) - MT027 UCAR‑T IIT (ChiCTR2100047968): ASCO 2023/2024 abstracts reported favorable tolerability with no grade ≥3 toxicities; 12‑month OS 85.7% (95% CI 48.7–97.4) in one analysis; PK/PD showed CSF persistence and cytokine increases. These are single‑center, early‑phase data. (ascopubs.org)

4SCAR‑276 (B7‑H3 CAR‑T; fourth‑generation) - Multicenter Phase I/II trial in B7‑H3–positive solid tumors (NCT04432649) is listed; as of the latest registry snapshots, no results are posted. (cdek.pharmacy.purdue.edu)

Safety

TX103 (NCT05241392; interim) - No dose‑limiting toxicities or treatment‑related deaths reported among 13 patients.
- Treatment‑related adverse events included cytokine release syndrome, increased intracranial pressure, headache, seizures, decreased consciousness, vomiting, and fever; most were grade 1–2. Three grade‑3 events occurred (increased intracranial pressure at dose level 2; seizure and decreased level of consciousness at dose level 3). (ascopubs.org)

Allogeneic B7‑H3 UCAR‑T (context) - Early reports noted no grade ≥3 toxicities, with most common events being fever and headache; no CRS/ICANS/GvHD observed in the presented dataset. (ascopubs.org)

Ongoing/registered trials

TX103 in grade 4 glioma (Phase 1, US/China sites; NCT06482905; recruiting since September 2024). Intracavitary and/or intraventricular dosing; planned 3+3 dose escalation. (cdek.pharmacy.purdue.edu)
TX103 investigator‑initiated rGBM study (NCT05241392; China; active, not recruiting). (cdek.pharmacy.purdue.edu)
4SCAR‑276 in B7‑H3–positive solid tumors (Phase I/II; NCT04432649; China). Fourth‑generation CAR with inducible caspase‑9 safety switch. (cdek.pharmacy.purdue.edu)
Additional pediatric B7‑H3 CAR‑T efforts (e.g., STRIvE‑02 Arm C exploring a B7‑H3xCD19 CAR plus pembrolizumab) are in early phase; efficacy is not yet established. (ascopubs.org)

Active trials using B7-H3 CAR-T

Found 4 active trials using this drug:

Hypofractionated Radiation in Combination With B7-H3-CAR T Cells for Pediatric Patients With Relapsed/Refractory Sarcomas

Sponsor: St. Jude Children's Research Hospital (other) Phase: 1 Start date: Oct. 30, 2025

TrialFetch AI summary: For children, adolescents, and young adults (≤21 years) with relapsed/refractory B7-H3 (CD276)–positive sarcomas (including osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, and other soft-tissue sarcomas) who have at least one lesion amenable to hypofractionated radiation. Treatment is hypofractionated radiation priming to ≥1 tumor site with fludarabine/cyclophosphamide lymphodepletion followed by IV infusion of autologous B7-H3–directed CAR T cells (genetically engineered T cells targeting the tumor antigen B7-H3).

ClinicalTrials.gov ID: NCT07222735

Phase I Clinical Trial of Autologous B7-H3 Chimeric Receptor (CAR) T Cells in Adults With Recurrent, Platinum Resistant Ovarian Tumors

Sponsor: Stanford University (other) Phase: 1 Start date: Nov. 11, 2024

TrialFetch AI summary: Adults with recurrent, platinum-refractory or -resistant epithelial ovarian cancer (including carcinosarcoma), ECOG 0–2, receive autologous B7‑H3 (CD276)–targeted CAR T cells after lymphodepletion, administered either intraperitoneally for peritoneal-only disease or intravenously if extra-peritoneal or IP not feasible. Investigational therapy targets broadly overexpressed B7‑H3; trial assesses feasibility/safety with dose escalation and early response signals.

ClinicalTrials.gov ID: NCT06646627

Phase I Clinical Trial of Autologous B7-H3 Chimeric Antigen Receptor T Cells (B7-H3CART) in Children and Young Adults With Relapsed or Refractory Solid Tumor Expressing B7-H3 Target

Sponsor: Crystal Mackall, MD (other) Phase: 1 Start date: July 11, 2024

TrialFetch AI summary: Children and young adults (2–30 years) with relapsed/refractory solid tumors (e.g., neuroblastoma, sarcomas, Wilms tumor) after standard therapy receive lymphodepleting fludarabine/cyclophosphamide followed by a single IV infusion of autologous B7-H3–directed CAR T cells (targets CD276). B7-H3 expression testing is required on tissue (positivity not mandatory); key exclusions include uncontrolled infection, active viral hepatitis/HIV, recent significant cardiac disease, untreated brain metastases, and need for systemic immunosuppression.

ClinicalTrials.gov ID: NCT06500819

B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

Sponsor: St. Jude Children's Research Hospital (other) Phase: 1 Start date: July 6, 2022

TrialFetch AI summary: Pediatric and young adult patients (≤21 years) with measurable, relapsed/refractory B7‑H3 (CD276)–positive solid tumors, including CNS involvement, receive lymphodepleting fludarabine/cyclophosphamide followed by a single IV infusion of autologous B7‑H3–targeted CAR T cells. The investigational therapy uses second‑generation CAR T cells engineered to recognize B7‑H3 to mediate antigen-directed cytotoxicity, with dose escalation to define safety and preliminary activity.

ClinicalTrials.gov ID: NCT04897321