NCT06825455

Allogeneic B7H3 CAR-γδT Cell Therapy for Advanced Solid Tumors

Clinical Study of the Safety and Tolerability of B7H3 CAR-γδT Cell Injection in the Treatment of Advanced Solid Tumors

• Status: Not Yet Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Peking University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

γδT cells can directly recognize non-peptide tumor antigens, such as IPP phosphorylated metabolites, without relying on specific major histocompatibility complexes (MHCs). This unique characteristic leads to a lower risk of graft-versus-host disease (GVHD). The clinical safety of γδT cells in allogeneic tumor therapies has been validated multiple times, highlighting their significant potential in developing universal CAR-T cell therapies. B7H3 (CD276), a member of the B7 negative co-stimulatory molecule family, is minimally expressed or absent in normal tissues but highly expressed in various tumor tissues. As a result, B7H3 is regarded as a highly promising tumor-associated antigen and a universal drug target with substantial therapeutic potential. By utilizing γδT cells as carrier cells, the development of universal B7H3 CAR-γδT cell injections for advanced solid tumors can effectively address risks such as autologous cell preparation failure and treatment delays. This innovative approach offers a highly efficient solution for solid tumor treatment and holds great promise for advancing immunotherapy in this field

Detailed description

This study is an open-label, dose-escalation exploratory clinical trial using γδ T cells derived from healthy donors, genetically engineered to express a chimeric antigen receptor (CAR) targeting B7H3 on their membrane. Preclinical in vitro and in vivo experiments demonstrated the modified CAR-γδ T cells possess specific cytotoxicity against B7H3-positive tumor cells. According to the patients' disease conditions, they were divided into an intravenous infusion group and an intraperitoneal infusion group. Both groups underwent a dose-escalation study using the "3+3" design.

Conditions

• Advanced Solid Tumors
• Ovarian Cancers
• Peritoneal (metastatic) Cancer

Interventions

Type	Name	Description
DRUG	Fludarabine	Intravenous infusion group:30mg/m2 x 3 days (Day-4\~-2)
DRUG	Cyclophosphamide	Intravenous infusion group:500mg/m2 x 3 days (Day-4\~-2)
BIOLOGICAL	B7H3 CAR-γδT cells	A single infusion of 6.0×107 CAR+ cells, 2.0×108CAR+ cells, and 6.0×108CAR+ cells

Timeline

• Start date: 2025-03-01
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2025-02-13
• Last updated: 2025-02-13

Locations

1 site across 1 country: China