NCT03170141

Immunogene-modified T (IgT) Cells Against Glioblastoma Multiforme

Immunogene-modified Antigen-specific T (IgT) Cells for the Treatment of Glioblastoma Multiforme

• Status: Enrolling By Invitation
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Shenzhen Geno-Immune Medical Institute · Academic / Other
• Sex: All
• Age: 6 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This study aims to treat patients who have been diagnosed with brain cancer glioblastoma multiforme (GBM) including diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG). The treatment combines two different approaches to fight cancer: immune modulators and antigen-specific T cells. Immune checkpoint antibodies have been tested on various tumors with good outcomes. GBM is known to express increased levels of certain antigens that can be targeted by T cells including chimeric antigen receptor-modified T (CAR-T) cells and tumor antigen specific cytotoxic lymphocytes (CTLs). In this study, the gene-modified T cells specific for GBM antigens will be combined with immune modulatory gene-modified dendritic cells (DCs) as individualized treatment regimens to treat patients.

Detailed description

Background: Glioblastoma multiforme (GBM) is the most dangerous and aggressive form of brain cancer. Chimeric antigen receptor (CAR)-modified T cells have been shown to mediate long-term durable remissions in recurrent or refractory hematopoietic malignancies, and thus the CAR-T therapy approach is also considered a promising treatment against GBM. Some surface antigens such as GD2 and CD56 have been targeted as potential GBM antigens. In addition, certain antigens are highly specific in GBM, such as epidermal growth factor receptor variant EGFRviii and metastasis related antigen CD44v6. Tumor microenvironment is known to suppressive anti-cancer immune responses. Many immune checkpoint inhibitors have demonstrated marked anti-tumor activities. For example, CD276 is a member of the B7 family of immune checkpoint proteins, and CD276-specific CAR-T cell therapy have been considered a potential brain tumor microenvironment treatment. Besides immune checkpoint inhibitor antibodies, antigen-specific T cells modified with immune modulatory genes (IgT) such as genes encoding immune checkpoint inhibitors may be applied. Combination of tumor targeting and immune modulatory activities, the IgT cells could target both the tumor cells and the tumor microenvironment.

Conditions

• Glioblastoma Multiforme of Brain
• Brain Cancer

Interventions

Type	Name	Description
BIOLOGICAL	Antigen-specific IgT cells	Tumor antigen-specific IgT cells are infused intravenously . Drug: cyclophosphamide 250 mg/m\^2 d1-3; Drug: Fludarabine 25mg/m\^2 d1-3

Timeline

• Start date: 2017-05-31
• Primary completion: 2027-07-31
• Completion: 2027-12-31
• First posted: 2017-05-30
• Last updated: 2025-01-20

Locations

1 site across 1 country: China