Allogeneic γδT Cells in Glioblastoma (ABOUT)

Peking University

Status: Enrolling

Conditions: Glioblastoma (GBM); Glioblastoma Multiforme (GBM)

Treatments: Drug: Allogeneic γδ T (ABOUT) cells

Study type: Interventional

Funder types: Other

Identifiers

NCT07144735

M20250397

Details and patient eligibility

About

This first-in-human clinical study aims to evaluate the safety and feasibility of locally delivered, allogeneic γδ T cells (genetically edited with ARIH1 and BCL11b knockout, designated ABOUT γδT cells) in patients with glioblastoma multiforme (GBM). The engineered effector cells are delivered via localized administration to selectively target and eliminate residual GBM cells. ABOUT: ARIH1 and BCL11b knockOUT γδ T cells.

Enrollment: 18 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female, age 18-70 years old (both ends included)

2. At least one evaluable lesion with previous biopsy or pathohistologic confirmation of glioblastoma (WHO grade IV), with imaging suggestive of continued progression or recurrence after comprehensive treatment

3. Karnofsky Performance Status (KPS) ≥ 60%

4. Life expectancy > 4 weeks

5. Patients who completed radiotherapy or systemic therapies (including temozolomide/bevacizumab or other agents) for at least 4 weeks prior to enrollment. All prior treatment-related toxicities should be defined as ≤ grade 1 (except for toxicities such as alopecia or leukoplakia) according to the Common Terminology Standard for Adverse Events (CTCAE 6.0)

6. Must be able to undergo an MRI with contrast

7. Must have adequate organ and marrow function as defined below:

   • White blood cell count (WBC) ≥ 3 x 10^9/L
   • Absolute neutrophil count (ANC) > 1 x 10^9/L
   • Hemoglobin (Hb) ≥ 90 g/L
   • Platelet (PLT) ≥ 80×10^9/L
   • Albumin transaminase (ALT) & albumin transaminase (AST) < 1.5 × institutional upper limit of normal (ULN)
   • Serum creatinine (Cr) < 1.5 x institutional ULN
   • Total bilirubin < 1.5 x institutional ULN
   • PT & PTT ≤ 1.25 x institutional ULN

8. No obvious hereditary diseases

9. Normal cardiac function with left ventricular ejection fraction >55%

10. No bleeding and coagulation disorders

11. Absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to ABOUT γδT cell infusion and/or there aren't any indications of meningitis

12. Fertile women must have had a pregnancy test with a negative result within 7 days prior to the start of treatment, and subjects are willing to use contraception (hormonal or barrier method of birth control or abstinence) during the clinical trial and for 6 months after the last cell infusion; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately

13. Signed, written informed consent

Exclusion criteria

1. Active hepatitis B or C virus, HIV infection, or other untreated active infection
2. Pregnant and lactating women
3. Participants with organ failure
4. Participants with a chronic disease requiring immunologic or hormonal therapy
5. Participants with an allergy to immunotherapy and related cells
6. Participants with uncontrolled intercurrent illness
7. Participants with psychiatric illness/social situations that would limit compliance with study requirements
8. Participants with a history of organ transplantation or who are awaiting organ transplantation

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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18 participants in 3 patient groups

Low dose

Experimental group

Description:

Dose 1: 7x10\^7 ABOUT γδT, local administration every 3-4 weeks

Treatment:

Drug: Allogeneic γδ T (ABOUT) cells

Medium dose

Experimental group

Description:

Dose 2: 1.1x10\^8 ABOUT γδT, local administration every 3-4 weeks

Treatment:

Drug: Allogeneic γδ T (ABOUT) cells

High dose

Experimental group

Description:

Dose 3: 1.6x10\^8 ABOUT γδT, local administration every 3-4 weeks

Treatment:

Drug: Allogeneic γδ T (ABOUT) cells