B7-H3-CAR T Cells for Brain Tumor

Overseen By Jean Laboe, MSN, RN

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: St. Jude Children's Research Hospital

Must be taking: Anti-seizure medication

Must not be taking: Live vaccines

Disqualifiers: Immunodeficiency, HIV, Severe infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using B7-H3-CAR T cells, a type of immunotherapy, for young people with specific brain tumors. The main goal is to determine the safest highest dose for patients. There are two groups: one with non-brainstem tumors that have recurred or resisted other treatments, and another with diffuse midline glioma. Participants should have a primary brain tumor that frequently presents challenges, such as not responding to standard treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

Yes, you will need to stop certain medications before joining the trial. Chemotherapy and biologic therapy must be stopped at least 7 days before enrollment, and antibody therapy must be stopped for at least 3 half-lives or 30 days, whichever is shorter. Corticosteroids must be stable or decreasing for at least 1 week before enrollment, with a maximum dose specified.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that B7-H3-CAR T cells, a treatment where immune cells are modified to attack cancer cells, have undergone testing. In an initial human trial, young patients with a serious brain tumor called DIPG received these cells. The treatment proved tolerable, as patients managed it without severe side effects.

These studies suggest that B7-H3-CAR T cells might be a safe option for children and young adults with certain brain tumors. However, since this is a Phase 1 trial, the primary goal is to determine the safest dose. While there is some evidence of safety, more research is needed to fully understand its tolerability. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for brain tumors, which typically involves surgery, radiation, and chemotherapy, B7-H3-CAR T cells offer a novel approach by harnessing the immune system to specifically target cancer cells. This treatment is unique because it uses genetically engineered T cells to attack B7-H3, a protein commonly found on the surface of certain tumor cells but not on most normal cells. Researchers are excited about this treatment because it has the potential to precisely target and destroy cancer cells while sparing healthy tissue, which could lead to fewer side effects and improved outcomes for patients with difficult-to-treat brain tumors.

What evidence suggests that B7-H3-CAR T cells might be an effective treatment for primary CNS tumors?

Research has shown that B7-H3-CAR T cells could aid in treating brain tumors, particularly in children. These cells target and attack a protein called B7-H3, found on many tumor cells. Lab studies have demonstrated their effectiveness against solid tumors and brain tumors in children. In earlier trials, patients with aggressive brain tumors, such as diffuse intrinsic pontine glioma (DIPG), tolerated B7-H3-CAR T cells. In this trial, participants with diffuse midline gliomas (DMG) will join Arm B, while those with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors will join Arm A. Although the research remains in its early stages, the results offer promise for conditions with limited treatment options. ^{1 2 3 4 6}

Who Is on the Research Team?

Christopher DeRenzo, MD

Principal Investigator

St. Jude Children's Research Hospital

Kelsey Bertrand

Principal Investigator

St. Jude Children's Research Hospital

Giedre Krenciute, PhD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

The Loc3CAR trial is for children and young adults up to 21 years old with primary brain tumors. Participants must have measurable disease, a life expectancy over 8 weeks, and be able to perform daily activities at least half of the time (Karnofsky/Lansky score ≥50). They should not have severe infections or immune deficiencies, non-programmable ventricular shunts, or any condition that could affect study results.

Inclusion Criteria

Screening Eligibility: For Cohort B, must meet one of the following criteria: Adequate tumor tissue for central pathology review, Brainstem high-grade neoplasm with available imaging for central review, Life expectancy of > 12 weeks, Adult patient, parent, or legal guardian can understand and sign a written informed consent document

I am a man who can father children and agree to use birth control.

Procurement and T-cell Production Eligibility: Estimated life expectancy of >12 weeks

Exclusion Criteria

Screening Eligibility: Clinically significant medical disorders compromising ability to tolerate protocol therapy or interfere with study procedure

Procurement and T-cell Production Eligibility: Participant has a non-programmable ventricular shunt, Known primary immunodeficiency or acquired immunodeficiency, Known HIV positivity, Severe intercurrent bacterial, viral, or fungal infection, Rapidly progressive disease, Known underlying medical condition not in the best interest of the participant, Unwilling or unable to provide consent for a 15-year long-term follow-up study

Treatment Eligibility: Participant has a non-programmable ventricular shunt, Known primary immunodeficiency or acquired immunodeficiency, Known HIV positivity, Severe intercurrent bacterial, viral, or fungal infection, Cardiovascular conditions within 6 months prior to study entry, Receiving therapy during the 'wash-out' period, Rapidly progressing disease, Received live vaccines within 30 days, Known underlying medical condition not in the best interest of the participant, Unwilling or unable to provide consent for a 15-year long-term follow-up study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive four B7-H3-CAR T cell infusions over a 4 week period via a CNS reservoir catheter

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Long-term follow-up

Participants continue follow-up on an institutional protocol to complete 15 years post-infusion

15 years

What Are the Treatments Tested in This Trial?

Interventions

• B7-H3-CAR T cells

Trial Overview This Phase I trial tests B7-H3-CAR T cells delivered directly into the central nervous system via a catheter in patients with two types of brain tumors: relapsed/refractory non-brainstem tumors (Cohort A) and high-grade brainstem neoplasms (Cohort B). The goal is to determine the highest safe dose through six infusions over eight weeks.

How Is the Trial Designed?

Group I: Arm B (diffuse midline gliomas [DMG]) Experimental Treatment 1 Intervention

Patients with DMG.

Group II: Arm A (relapsed/refractory CNS tumors) Experimental Treatment 1 Intervention

Patients with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

B7-H3 CAR T cells have shown significant antitumor activity in various pediatric solid tumor models, including osteosarcoma and medulloblastoma, indicating their potential as a treatment option for relapsed pediatric malignancies.

The effectiveness of B7-H3 CAR T cells is linked to the density of the B7-H3 antigen on tumor cells, suggesting that this therapy could be selectively effective against tumors with high antigen expression while minimizing effects on normal tissues with lower expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors. Majzner, RG., Theruvath, JL., Nellan, A., et al.[2021]

Atypical teratoid/rhabdoid tumors (ATRTs) express the B7-H3 protein, which is crucial for their growth and can be targeted for therapy, highlighting its potential as a therapeutic target for this aggressive pediatric cancer.

Using B7-H3-targeted CAR T cells delivered directly into the brain showed faster and more effective tumor suppression in mouse models compared to traditional intravenous delivery, suggesting that localized treatment may reduce systemic side effects and improve outcomes for children with ATRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors. Theruvath, J., Sotillo, E., Mount, CW., et al.[2022]

B7-H3 is highly overexpressed in glioblastoma (GBM) compared to normal brain tissue, making it a promising target for CAR-T cell therapy, as shown by immunohistochemistry in 76% of analyzed specimens.

B7-H3-redirected CAR-T cells effectively targeted and controlled tumor growth in GBM cell lines and patient-derived neurospheres in both in vitro and in vivo models, indicating their potential as a new treatment strategy for GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7-H3-redirected chimeric antigen receptor T cells target glioblastoma and neurospheres. Nehama, D., Di Ianni, N., Musio, S., et al.[2021]

B7-H3 is frequently overexpressed in glioblastoma (GBM) and correlates with higher malignancy and poorer survival rates, making it a promising target for treatment.

CAR T cells engineered to target B7-H3 showed significant antitumor effects in both laboratory tests and in animal models, leading to longer survival compared to control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma. Tang, X., Zhao, S., Zhang, Y., et al.[2020]

B7-H3 is a promising target for immunotherapy in treating various brain cancers, as it helps create a tumor-friendly environment that allows cancer cells to grow and resist treatment.

Preclinical studies and early-phase trials have shown that targeting B7-H3 can lead to effective anti-tumor responses with manageable toxicity, and ongoing clinical trials are exploring its use in combination therapies for difficult-to-treat brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7-H3 in Brain Malignancies: Immunology and Immunotherapy. Guo, X., Chang, M., Wang, Y., et al.[2023]

B7-H3 is a promising target for cancer immunotherapy due to its consistent expression in tumors and limited presence in healthy tissues, making it a suitable candidate for CAR-T therapy.

A newly developed anti-B7-H3 CAR-T demonstrated strong anti-tumor activity in vitro and showed sustained proliferation in response to repeated antigen challenges, indicating its potential effectiveness in treating resistant neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel anti-B7-H3 chimeric antigen receptor from a single-chain antibody library for immunotherapy of solid cancers. Birley, K., Leboreiro-Babe, C., Rota, EM., et al.[2022]

Citations

1. nature.com nature.com/articles/s41591-024-03451-3

Intracerebroventricular B7-H3-targeting CAR T cells for ... This completed first-in-human trial shows that repetitive ICV dosing of B7-H3 CAR T cells in pediatric and young adult patients with DIPG is tolerable.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11457631/

CAR-T cells for H3K27-altered diffuse midline gliomas Among the pediatric brain tumors, diffuse midline gliomas (DMG) harboring a mutation in histone H3K27 have the deadliest prognosis [1].

3. sciencedirect.com sciencedirect.com/science/article/pii/S2772610X24000199

CAR T cells redirected to B7-H3 for pediatric solid tumors CAR T cells targeting B7-H3, a pan-cancer antigen, demonstrate potent preclinical activity against pediatric solid tumors and brain tumors.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05835687

Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for ... Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR ...

5. biorxiv.org biorxiv.org/content/10.1101/2025.09.01.673023v1.full-text

Preclinical efficacy of combinatorial B7-H3 CAR T cells and ... This work offers a biologically-informed, clinically translatable strategy integrating small molecule therapeutics with CAR T cell therapy and ...

6. cell.com cell.com/trends/cancer/fulltext/S2405-8033(23)00134-6

CAR T cell therapies for diffuse midline glioma We highlight the current landscape of CAR T cell therapy for DMG, the role the TIME may play in the response, and strategies to overcome treatment obstacles.