CAR-T Therapy for Glioblastoma: Which Trials Are Open

CAR-T cell therapy - engineered immune cells designed to recognize and destroy tumor cells - is an experimental approach being tested for glioblastoma. If standard treatment options have not worked, knowing that trials exist is one thing. Knowing whether you qualify, and how to actually apply, is another. This guide covers both.

What Is CAR-T Cell Therapy?

CAR-T stands for chimeric antigen receptor T-cell. The process starts with a blood draw. A laboratory then modifies the patient's own T cells - a type of immune cell - by attaching a synthetic receptor, the chimeric antigen receptor, to the cell surface. That receptor is engineered to recognize one specific protein found on tumor cells. When the modified cells encounter that protein, they attack and kill the cell carrying it.

The modified cells are multiplied in large numbers over several weeks, then infused back into the patient. The goal is that they will seek out tumor cells expressing the target protein while leaving healthy tissue alone.

CAR-T therapy has produced durable remissions in some blood cancers, including certain leukemias and lymphomas. In solid tumors like glioblastoma, the challenge is much harder. The blood-brain barrier limits how well infused cells reach the tumor from the bloodstream. The tumor also actively suppresses the immune environment around it, blunting T-cell activity. New cell designs and new delivery methods may help overcome these obstacles.

Why Glioblastoma Presents Specific Obstacles

Two core biology problems make GBM harder to treat with CAR-T than blood cancers.

First, glioblastoma tumors are heterogeneous. Different cells within the same tumor can express different surface proteins. A CAR-T product targeting one protein may miss tumor cells without it. Over time, tumor cells can also downregulate or lose that surface protein entirely - a process called antigen escape - allowing the cancer to evade the treatment.

Second, GBM creates an immunosuppressive microenvironment. The tumor releases signals that suppress T-cell function in the tissue surrounding it. Newer CAR-T designs tackle this by targeting two antigens at the same time, or by equipping the T cells with additional signals that help them resist immunosuppression inside the tumor.

Which Tumor Proteins Do Current Trials Target?

Eligibility for a specific CAR-T trial depends almost entirely on whether your tumor expresses the protein that trial targets. The proteins most commonly studied in active or recently completed trials are listed below. Each requires a specific test to confirm expression in your tumor tissue.

• EGFRvIII - A mutant form of the epidermal growth factor receptor that appears almost exclusively on tumor cells and is largely absent from normal brain tissue. It is present in a significant subset of GBM tumors. Confirming it requires specialized molecular testing, typically next-generation sequencing or immunohistochemistry of tumor tissue. If your original pathology report did not include this test, it can often be ordered on your archived biopsy sample.
• IL13Ra2 (IL-13 receptor alpha-2) - Expressed by the majority of high-grade gliomas and associated with aggressive tumor behavior. Multiple published trials have delivered CAR-T cells targeting this protein directly into the tumor cavity or the brain's fluid-filled spaces.
• GD2 - A molecule found on the surface of GBM cells and rare in normal adult brain tissue. Research suggests it may be expressed in a subset of GBM patients, and CAR-T constructs enhanced by additional immune signals have shown activity in preclinical models.
• B7-H3 - An immune checkpoint protein overexpressed on many GBM tumors. Early-phase trials are evaluating CAR-T cells targeting this antigen, including in combination with IL13Ra2.
• CD70 - An antigen being studied in early-phase trials for both adult and pediatric high-grade glioma.

How Are CAR-T Cells Delivered Into a Brain Tumor?

This is where GBM trials look very different from the CAR-T infusions used for blood cancer. In leukemia, infusing cells into a vein is enough because the malignant cells are circulating in the blood. For a solid tumor inside the skull, direct delivery into or near the tumor tends to work better.

According to a published phase 1 trial of IL13Ra2-targeting CAR-T cells in recurrent high-grade glioma, researchers evaluated three delivery routes: intratumoral (directly into the tumor mass), intraventricular (into the brain's fluid-filled ventricles), and a combination of both. Locoregional delivery - infusing cells close to or inside the tumor - helped CAR-T cells reach and persist in tumor tissue. The trial also confirmed feasibility, with immune activation measurable in the cerebrospinal fluid.

This delivery approach often involves a minor surgical step before treatment starts. An Ommaya reservoir - a small dome-shaped device placed just beneath the scalp - may be implanted to allow repeated infusions without requiring repeated open surgery. Some trials instead use a catheter in the tumor resection cavity from the original operation.

Which CAR-T Trials Are Currently Enrolling?

Enrollment status changes frequently. Always confirm current status at ClinicalTrials.gov by entering the NCT number listed below. The trials below were recruiting or recently active based on public registry data through mid-2026, alongside the National Brain Tumor Society's rolling clinical trial updates, which come out twice per year and cover new openings after any article's publication date.

• CARv3-TEAM-E (NCT05660369) - Based at Massachusetts General Hospital. Evaluates a CAR-T product in adults with recurrent or newly diagnosed EGFRvIII-positive GBM. The construct also releases a molecule that blocks a second tumor growth signal, giving it a dual mechanism inside the tumor microenvironment.
• IL13Ra2-Targeting CAR-T for Recurrent Glioma (NCT06355908) - Targets WHO grade 4 gliomas with confirmed IL13Ra2 expression. Open to adults aged 18 to 75 who have relapsed or progressed after standard treatment, with a Karnofsky Performance Status (KPS) score of 50 or above.
• EGFR/IL13Ra2 Pool-CAR T Cells (NCT07544992) - A locoregional delivery trial for recurrent or progressive high-grade gliomas. Uses two CAR-T products delivered simultaneously, one targeting EGFR and one targeting IL13Ra2, to reduce the risk of antigen escape.
• EGFRvIII Metabolic CAR-T (NCT07244666) - Evaluates a CAR-T product engineered to function better in the nutrient-poor tumor microenvironment. Requires EGFRvIII expression confirmed by next-generation sequencing.
• E-SYNC Trial (NCT06186401) at UCSF - Studies T cells that switch on a second anti-tumor receptor only after detecting a specific tumor signal - a circuit designed to limit off-target activity. Eligibility requires MGMT-unmethylated GBM with EGFRvIII expression.
• TGFbR2KO/IL13Ra2 CAR-T (NCT06815029) - Targets IL13Ra2 with cells additionally engineered to resist TGF-beta, a major immunosuppressive signal that GBM tumors use to shut down T-cell activity. Open to patients with recurrent or progressive GBM and grade 3 or 4 IDH-mutant astrocytoma.

How Do You Know If You Might Qualify?

Trial sites use defined inclusion and exclusion criteria to determine eligibility, not general clinical impression. Most GBM CAR-T trials share several common requirements, though specifics vary by trial and by institution.

1. Confirmed GBM diagnosis. Virtually all trials require a histologically confirmed diagnosis of WHO grade 4 glioma or glioblastoma, documented by a biopsy or surgical pathology report.
2. Recurrence or progression after standard treatment. Most trials target patients who have relapsed after at least one line of standard therapy - typically surgery, radiation, and temozolomide chemotherapy. A smaller number accept newly diagnosed patients with specific molecular features such as EGFRvIII expression and MGMT-unmethylated status.
3. Antigen expression in your tumor tissue. Your archived tumor sample must contain the protein the trial targets. Doctors confirm this with immunohistochemistry or molecular sequencing. If your original testing did not cover the relevant antigen, doctors often can order additional testing on stored tissue.
4. Adequate functional status. Most trials use the Karnofsky Performance Scale (KPS). Most trials require a score of 50 to 70 or above, reflecting the ability to perform at least some self-care tasks and tolerate the monitoring visits a trial schedule demands.
5. Prior treatment limits. Some trials cap how many prior chemotherapy regimens are allowed. Others exclude patients who have previously received certain immunotherapy agents, including checkpoint inhibitors.
6. Organ function within acceptable range. Your blood counts and liver and kidney function must fall within the trial's limits before you can enroll.
7. Tissue availability. Most trials need an archived tumor block or pathology slides for antigen testing before formal screening. If no stored tissue is available, some trials require a new biopsy before enrollment.

If your original pathology work-up did not include EGFRvIII or IL13Ra2 expression testing, doctors can often order additional testing on stored tissue. This is why getting an international pathology second opinion before contacting a trial center is practical - a specialist re-review may uncover antigen expression data that either opens or closes specific trials for you.

Steps to Take Before You Contact a Trial Site

1. Gather your original pathology report, surgical report, and any molecular testing already done - MGMT methylation, IDH status, EGFR amplification, EGFRvIII, and any comprehensive genomic profiling panel if available.
2. Search ClinicalTrials.gov using the condition "glioblastoma" and the intervention keyword "chimeric antigen receptor" or "CAR-T." Filter by "Recruiting" status and your country or region.
3. Read the eligibility criteria section on each trial page before making contact. Inclusion and exclusion criteria are listed there in plain language.
4. Ask your current neuro-oncologist whether the pathology department still has your original tumor block or slides and can send them for additional staining or sequencing.
5. Contact the trial coordinator listed on the trial's ClinicalTrials.gov page before booking travel. Most coordinators offer an informal pre-screening call or email to rule out obvious ineligibility before a formal appointment is scheduled.
6. If you are outside the trial's home country, ask the coordinator explicitly whether the trial accepts international patients and what the expected visit frequency looks like. Some trials require weekly or biweekly in-person visits during treatment, which affects feasibility for families traveling from abroad.

Spend time exploring all your options before choosing a specific trial. You can also get a remote second opinion from specialists who can review your scans, pathology, and treatment history and help match your molecular profile to available trials.

For a broader framework on how to evaluate any trial before signing an informed consent document - including what questions to ask about risks, what your rights are as a participant, and how to weigh access to a new therapy against the practical demands of participation - see Evaluating a Glioblastoma Clinical Trial Before You Enroll.

What Do Early Results Actually Show?

CAR-T therapy for glioblastoma is experimental. Most active trials are phase 1, where the primary goal is establishing safe dosing - not proving survival benefit. That context is important when you encounter results from early studies.

According to a published review of CAR-T immunotherapy in glioblastoma, some patients in early trials have shown meaningful tumor responses. In the phase 1 IL13Ra2 locoregional trial, one patient with multifocal recurrent GBM showed 77 to 100 percent reduction in tumor volume in treated areas following intraventricular infusions, with clinical benefit lasting approximately 7.5 months. That is a single case report, not a representative success rate. But it confirms that a biological response can occur, and it shaped the design of follow-on trials now in progress.

Across published early-phase data, responses - when they occur - are often partial and temporary. Antigen escape remains a major reason for eventual progression even in patients who initially respond. Dual-targeting approaches like the EGFR/IL13Ra2 pool trial are designed specifically to address that limitation.

Very few CAR-T approaches for GBM have reached phase 2. Entering a phase 1 trial means participating in research that may benefit future patients alongside yourself. It also means close monitoring by a specialist team at a major cancer center and access to a therapy unavailable outside a research setting. The possibility of a response is real. A guarantee is not.

The article Glioblastoma Immunotherapy Trials and Your Molecular Profile explains which molecular tests carry the most weight when evaluating immunotherapy options across multiple trial types, including CAR-T.

When to Talk to Your Doctor

Talk to your neuro-oncologist before contacting any trial site if you have not yet had comprehensive molecular testing that includes EGFRvIII and IL13Ra2 expression - antigen confirmation is a prerequisite for most CAR-T trials, and without it, pre-screening conversations cannot advance. Also seek guidance if your functional status has changed recently and you are unsure whether you still meet KPS thresholds, or if you are still on active treatment with temozolomide or bevacizumab, since most CAR-T trials require a washout period before enrollment begins.

This article is for general information and is not a substitute for medical advice. Always consult your oncologist or care team about your specific situation.