NK Cell Therapy for Brain Cancer

(NK HGG Trial)

Overseen By Lauren Rayman

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Nationwide Children's Hospital

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Pregnancy, HIV, Uncontrolled infection, others

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

Compensation: Varies

Number of Visits: 3

Duration: 48 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using NK cells, a type of immune cell, to combat brain cancer. The goal is to determine if these cells can safely and effectively target and reduce certain brain tumors that have not responded to other treatments. Patients with a recurrent or resistant malignant CNS tumor who might qualify for a specific type of surgical device placement could be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop certain medications before enrolling. For example, you must stop myelosuppressive anticancer therapy at least 21 days before, and corticosteroids like dexamethasone must be on a stable or decreasing dose for at least 1 week prior. Check with the trial team for specific guidance on your current medications.

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

Research has shown that NK cell therapy is generally safe for treating brain cancer. In one study on children with brain tumors, multiple injections of NK cells caused no serious side effects. Patients did not experience severe reactions from the treatment. Another study found that using NK cells with other treatments completely controlled the disease in a small group of patients with recurring brain cancer.

These results suggest that NK cell therapy is well-tolerated and could be a promising treatment option. Although this trial remains in the early stages, the absence of serious side effects in previous research is encouraging for potential participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain cancer, which often involve chemotherapy, radiation, or surgery, NK cell therapy uses the body's own immune system to fight the disease. This treatment is unique because it involves infusing patients with specially prepared natural killer (NK) cells that are designed to target and destroy cancer cells. Researchers are particularly excited about this approach because it offers a new mechanism of action—harnessing the body's natural defenses—potentially leading to more effective and personalized cancer treatment. Additionally, the precision of targeting cancer cells may reduce the side effects associated with traditional treatments.

What evidence suggests that NK cell therapy might be an effective treatment for brain cancer?

Research shows that NK (natural killer) cell therapy, which participants in this trial will receive, could be promising for treating brain cancer. Early results found that it controlled the disease in all patients in a small group with recurrent glioblastoma, a type of brain cancer. NK cells can target and destroy cancer cells without harming normal cells. Studies have shown their effectiveness against various cancers, including melanoma and glioblastoma. This suggests that NK cell therapy might be a powerful way to fight brain cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Sara Khan, MD

Principal Investigator

Nationwide Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children and teens (3-18 years old) with high-grade, recurrent brain tumors who've had prior radiation treatment. They must be healthy enough for surgery, have good organ function, not be on steroids or certain other medications, and agree to use birth control if applicable.

Inclusion Criteria

My brain tumor is a high-grade type but has not spread beyond the brain.

My liver and kidney functions are within normal limits.

I have recovered from side effects of my previous cancer treatments.

Exclusion Criteria

My tumor cannot be safely accessed for NK cell therapy without risking brain damage.

My tumor affects both sides of my brain or has spread to the brain's lining.

I am on long-term steroid medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 12 cycles of TGFβi NK cell infusions, each cycle lasting 4 weeks with weekly infusions for 3 weeks followed by a rest week

48 weeks

Weekly visits for infusions during the first 3 weeks of each cycle

Dose-limiting toxicity (DLT) assessment

Assessment of dose-limiting toxicity during the first 28 days of treatment

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

What Are the Treatments Tested in This Trial?

Interventions

• NK cells

Trial Overview The study tests the safety and effects of injecting Natural Killer (NK) cells directly into the tumor over 12 weeks. Patients will receive weekly infusions in cycles of three weeks with a rest week following each cycle. The NK cell dose increases stepwise between patients.

How Is the Trial Designed?

Group I: NK cell infusion Experimental Treatment 1 Intervention

The TGFβi NK cell product on this trial will be manufactured in the Cell Based Therapy (CBT) Core facility at Nationwide Children's Hospital. Donors have been identified with specific universal-donor NK cell characteristics. The NK cells are collected from these donors via apheresis and then undergo CD3 depletion followed by a 2-week expansion. TGFβi NK cells are then generated by weekly stimulation with feeder cells and cultured in IL-2 and TGFβ. After 2 weeks, the TGFβi NK cells are washed and cryopreserved for future use. The expanded donor NK cell product will be manufactured prior to subject enrollment. Patients will receive 3 cycles of NK cell infusions over 12 weeks. Each cycle will consist of three weekly injections followed by a rest week (week 4). If patients have stable or improved disease and additional doses are available, patients may continue to receive therapy for a total of 12 cycles.

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Published Research Related to This Trial

The study demonstrated that injecting HER2-targeted CAR-NK cells into patients with recurrent glioblastoma is safe, with no dose-limiting toxicities or severe side effects like cytokine release syndrome observed in the nine patients treated.

Five out of nine patients experienced stable disease for 7 to 37 weeks after treatment, indicating potential efficacy, while the median overall survival was 31 weeks, suggesting that this approach could be a promising option for managing recurrent glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial injection of natural killer cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma. Burger, MC., Forster, MT., Romanski, A., et al.[2023]

Natural killer (NK) cells, which are often suppressed by glioblastoma (GB) tumors, can be activated ex vivo with cytokines to restore their ability to attack GB cells, suggesting their potential for immunotherapy.

Current research includes a phase I clinical trial using CAR-NK cells targeting the ErbB2 (HER2) antigen in glioblastoma patients, highlighting a promising approach to enhance NK cell specificity and efficacy against this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-Engineered NK Cells for the Treatment of Glioblastoma: Turning Innate Effectors Into Precision Tools for Cancer Immunotherapy. Burger, MC., Zhang, C., Harter, PN., et al.[2020]

Natural killer (NK) cells have strong antitumor capabilities and are being explored as potential therapies for brain tumors, despite their low presence in the tumor-infiltrating immune cells.

The review discusses various strategies to enhance NK cell effectiveness against brain malignancies, including sourcing therapeutic NK cells, combining them with other treatments, and engineering them to improve their ability to kill cancer cells, supported by preclinical and clinical trial evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NK cells in the brain: implications for brain tumor development and therapy. Balatsoukas, A., Rossignoli, F., Shah, K.[2023]

Citations

1. immunitybio.com immunitybio.com/initial-data-shows100-disease-control-in-5-out-of-5-patients-with-recurrent-glioblastoma-with-two-patients-in-near-complete-response-treated-with-immunitybios-anktiva-nk-cell-therapy-p/

Initial Data Shows 100% Disease Control in 5 Out of 5 ... All five patients achieved 100% disease control with the regimen that combines ANKTIVA, an IL-15 agonist being studied for its ability to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10741423/

Unlocking Glioblastoma Secrets: Natural Killer Cell Therapy ... Encouraging outcomes from clinical investigations underscore NK cells as a potentially effective modality for cancer therapy. Consequently, NK ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1525001625001686

Natural killer cell therapy targeting glioma stem cells in ... Recent studies have highlighted their effectiveness against various cancers, demonstrating significant cytotoxic activity against melanoma and ...

4. immunitybio.com immunitybio.com/glioblastoma/

Glioblastoma Cancer Clinical Trial First chemotherapy-free trial combining ANKTIVA, an IL-15 agonist, natural killer (NK) cell therapy, and Optune immune-stimulating device for ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07202611

Study Details | NCT07202611 | DC/NK Cell Therapy Validation of Cultured Cell Preparation Success: Assessing the proliferation rate, recovery rate, survival rate, and tumor-killing capacity of ...

6. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14314-6

The safety and feasibility of multiple intrathecal injections of ... Multiple intrathecal injections of allogeneic NK cells in pediatric gliomas were safe, without any serious adverse events (SAEs). The most ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11752833/

Research Progress of NK Cells in Glioblastoma Treatment A study shows that GBM exhibits the highest degree of NK cell infiltration among tumors when compared to that of breast cancer and melanoma, ...

8. cell.com cell.com/cancer-cell/fulltext/S1535-6108(24)00268-X?rss=yes

When playing the NK cell therapy card in glioblastoma, you ... Standard treatment involves surgical intervention followed by chemotherapy and radiation, with a 5-year survival rate of less than 10%. This ...