Evaluation of in Vitro Antitumor Activity of GD2 CAR-T Cells in Glioblastoma

NCT06764537 | Not Yet Recruiting DMC

• 1 other identifier: RIPH2: 2024-A02098-39 2022PI15
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Glioblastoma is a brain tumor with a very poor prognosis, affecting around 2,400 new patients every year. Current treatments do not provide good control of the disease. In view of the therapeutic impasse, it is necessary to develop new strategies. CAR-T cells (Chimeric antigen receptor T cells) represent a highly promising therapy for the treatment of incurable cancers, including glioblastoma. This treatment aims to destroy cancer cells by relying on the patient's own immune system. CAR-T cells are generated from the patient's own immune cells, more specifically T lymphocytes, which are genetically modified to express a tumor-specific receptor on their surface. CAR-T cells bind to tumor cells and cause their destruction. However, these cells have shown limited therapeutic power in the treatment of brain tumors. This is mainly due to the microenvironment surrounding the tumor, which is composed of immunosuppressive cells. These cells, and the molecules they secrete, help to reduce the activity of CAR-T cells that would otherwise reach the tumor. Little is currently known about these resistance mechanisms. The aim of this research is therefore to better understand these resistance mechanisms in order to propose a strategy for enhancing the therapeutic action of CAR-T cells in the treatment of glioblastoma. The main objective of this research is to evaluate the impact of the tumor environment on the antitumor efficacy of anti-GD2 CAR-T therapeutic cells in an in vitro glioblastoma model. Both tumor environment cells and CAR-T therapeutic cells will be generated from glioblastoma patient cells. The secondary objectives of this research are to

• Evaluate the impact of tumor environment targeting on the in vitro antitumor efficacy of anti-GD2 CAR-T therapeutic cells.
• Evaluate the quality/quantity of generated cells (CAR-T cells and tumor environment cells) in relation to glioblastoma patients.
• Evaluate the efficiency of the cell isolation technique (CAR-T cells and tumor environment cells)

Conditions

Glioblastoma

Keywords

Glioblastoma; GD2 CAR-T cells; Myeloid-derived suppressor cells; microenvironment

Outcome Measures

Primary Outcomes (3)

• Quantification of the number of residual tumor cells after in vitro co-culture in presence of CAR-T and MDSC cells

  Using in vitro cytotoxicity tests

  14 days after the blood sample realized at the inclusion visit

• The percentage of proliferative effector cells

  Using flow cytometry

  14 days after the blood sample realized at the inclusion visit

• The quantity of cytokines released

  Using ELISA tests

  14 days after the blood sample realized at the inclusion visit

Study Arms (1)

Blood collection (40 mL) of glioblastoma patients

EXPERIMENTAL

Procedure: Blood collection

Interventions

Blood collection PROCEDURE

Blood collection (40 mL) in glioblastoma patients

Blood collection (40 mL) of glioblastoma patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, adult (age ≥ 18 years)
• WHO 0 to 2
• Patient with a diagnosis of histologically proven de novo glioblastoma with non-mutated IDH status according to WHO 2021 classification
• Patient naïve to any treatment for this cancer
• Patient weighing ≥ 50 kg
• Patient able and willing to follow all study procedures in accordance with the protocol;
• Person affiliated to a social security scheme or beneficiary of such a scheme
• Person who has received full information on the organization of the clinical research and has signed an informed consent form

You may not qualify if:

• People with hematological malignancies
• People with a history of cancer \< 5 years old
• Immunocompromised (with immunodeficiency or current immunosuppressive therapy)
• Chronic inflammatory disease
• Person with current infection
• Anyone taking corticosteroids \>10mg/day on the day of blood sampling for research purposes
• Anyone with a contraindication to blood sampling
• Women of childbearing age without effective contraception
• Persons covered by articles L. 1121-5, L. 1121-7 and L1121-8 of the French Public Health Code Pregnant, parturient or breast-feeding women Minor (not emancipated) Adult subject to a legal protection measure (guardianship, curatorship, safeguard of justice) Persons of full age who are unable to give their consent
• Persons deprived of their liberty by a judicial or administrative decision, persons under psychiatric care under articles L. 3212-1 and L. 3213-1

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Study Sites (1)

Cell Therapy Unit, Nancy Hospital

Vandœuvre-lès-Nancy, 54500, France

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Loïc REPPEL, PharmD, PhD

CONTACT

+330383157938; l.reppel@chru-nancy.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 28, 2024
• First Posted: January 8, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 8, 2025

Record last verified: 2025-01

Locations

FR (1)