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

Trial Summary

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.

What data supports the effectiveness of the NK cell therapy for brain cancer?

Research shows that NK cells, a type of immune cell, can kill brain tumor cells, including gliomas and glioblastomas, which are aggressive brain cancers. Studies suggest that NK cells can be activated to fight these tumors, and new techniques like CAR-NK cells are being developed to enhance their ability to target and destroy cancer cells. ^{1 2 3 4 5}

Is NK cell therapy safe for humans?

Research on NK cell therapy, including clinical trials, suggests it is generally safe for humans, with studies focusing on brain tumors like glioblastoma. These trials are primarily in early stages, assessing safety and feasibility, and have shown promise without significant safety concerns reported. ^{1 3 4 6 7}

How is NK cell therapy different from other treatments for brain cancer?

NK cell therapy for brain cancer is unique because it uses natural killer cells, which are a type of immune cell, to directly target and destroy cancer cells. Unlike traditional treatments like surgery, chemotherapy, and radiation, NK cell therapy aims to enhance the body's own immune response to fight the tumor, potentially reducing side effects and improving outcomes. ^{1 3 5 8 9}

What is the purpose of this trial?

This trial involves giving patients special immune cells called NK cells through an infusion. It targets patients who may not respond well to standard treatments. The goal is to enhance the body's ability to fight harmful cells by increasing the number of NK cells. NK cells have attracted attention as a promising cancer immunotherapeutic target due to their ability to kill malignant cells and avoid healthy cells.

Research Team

Sara Khan, MD

Principal Investigator

Nationwide Children's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

NK cells in the brain: implications for brain tumor development and therapy. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Natural killer cell-related gene signature predicts malignancy of glioma and the survival of patients. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Advances in NK cell therapy for brain tumors. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Immunotherapy in gliomas: limitations and potential of natural killer (NK) cell therapy. [2013]

5. Switzerland pubmed.ncbi.nlm.nih.gov

CAR-Engineered NK Cells for the Treatment of Glioblastoma: Turning Innate Effectors Into Precision Tools for Cancer Immunotherapy. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Intracranial injection of natural killer cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma. [2023]

7. England pubmed.ncbi.nlm.nih.gov

CAR-Engineered NK Cells Targeting Wild-Type EGFR and EGFRvIII Enhance Killing of Glioblastoma and Patient-Derived Glioblastoma Stem Cells. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Natural killer cells in intracranial neoplasms: presence and therapeutic efficacy against brain tumours. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

ErbB2/HER2-Specific NK Cells for Targeted Therapy of Glioblastoma. [2021]