RNA-Lipid Particle Vaccines for Recurrent Glioblastoma

Overseen By Phuong Deleyrolle

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Florida

Must not be taking: Bevacizumab, Live vaccines

Disqualifiers: Active infection, Uncontrolled seizures, AIDS, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 17 months

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase I study to demonstrate the manufacturing feasibility and safety, and to determine the maximum tolerated dose (MTD) of RNA-LP vaccines in adult patients with recurrent glioblastoma.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be weaned off steroids or onto a low dose at the time of enrollment, and you cannot have received any live vaccines within 30 days prior to enrollment.

What data supports the effectiveness of the RNA-Lipid Particle Vaccines treatment for recurrent glioblastoma?

Research shows that RNA-Lipid Particle Vaccines can trigger strong immune responses against tumors by mobilizing immune cells and expanding specific T cell immunity, which was observed in early human trials for glioblastoma. Additionally, these vaccines have been safe and active in animal studies, suggesting potential effectiveness in treating this aggressive brain cancer. ^{1 2 3 4 5}

Is the RNA-Lipid Particle Vaccine safe for humans?

RNA-Lipid Particle Vaccines have been shown to be safe in early human trials for glioblastoma, and they were also safe in animal studies, including mice and dogs. ^{1 2 3 6 7}

How is the RNA-Lipid Particle Vaccine treatment for recurrent glioblastoma different from other treatments?

The RNA-Lipid Particle Vaccine is unique because it uses RNA to stimulate the immune system to target glioblastoma cells, potentially offering a more durable response compared to traditional treatments. This approach is novel as it combines RNA with lipid particles to enhance stability and delivery, which is not common in existing glioblastoma therapies. ^{2 3 5 6 8}

Research Team

Ashley Ghiaseddin, MD

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for adults with recurrent glioblastoma, a type of brain cancer. Participants must have evidence of tumor recurrence after standard treatments. Specific eligibility criteria are not provided here.

Inclusion Criteria

It has been over 90 days since my last radiation treatment.

Bone Marrow: ANC (Absolute neutrophil count) ≥ 1,500µl (unsupported), Platelets ≥ 100/µl (unsupported for at least 3 days), Hemoglobin > 8 g/dL

Any side effects from my previous treatments have mostly gone away.

Exclusion Criteria

I am currently being treated for an infection or have a disease that weakens my immune system.

My cancer has come back in more than one area, but the original cancer site is stable.

My tumor is located in the brainstem or spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 15 RNA-LP vaccines, with the first three being pp65 RNA-LP vaccines followed by monthly full dose RNA-LPs

17 months

Monthly visits for vaccine administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including up to 4 additional MRIs

4 weeks

Treatment Details

Interventions

• RNA-Lipid Particle (RNA-LP) Vaccines

Trial Overview The study is testing two types of RNA-Lipid Particle (RNA-LP) vaccines: pp65 RNA loaded lipid particles (DP1) and another set of RNA loaded lipid particles (DP2). It aims to find the highest dose patients can tolerate without severe side effects.

Participant Groups

Group I: Arm 2: pp65 RNA-LPs (DP1) after biopsy Experimental Treatment 2 Interventions

Randomized 1:1 to receive pp65 RNA-LPs (DP1) starting after tumor biopsy/resection. All patients will receive three pp65 RNA-LP vaccines (DP1) before receiving full dose monthly RNA-LPs (RNA loaded lipid particles, RNA-LPs, DP2).

Group II: Arm 1: pp65 RNA-LPs (DP1) before biopsy Experimental Treatment 2 Interventions

Randomized 1:1 to receive pp65 RNA-LPs (DP1) starting before tumor biopsy/resection. All patients will receive three pp65 RNA-LP vaccines (DP1) before receiving full dose monthly RNA-LPs (RNA loaded lipid particles, RNA-LPs, DP2).

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

A new method using lipid-particle delivery systems to enhance the immunogenicity of tumor-derived mRNA has shown promise in mobilizing immune cells and rejecting tumors in murine models, indicating its potential for cancer immunotherapy.

In a first-in-human trial for glioblastoma patients, RNA-LPAs successfully induced pro-inflammatory responses and expanded T cell immunity, suggesting they could be effective in treating poorly immunogenic tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mRNA aggregates harness danger response for potent cancer immunotherapy. Mendez-Gomez, HR., DeVries, A., Castillo, P., et al.[2023]

RNA-based immunotherapies, particularly RNA dendritic cell vaccines, have shown safety in a small phase I clinical trial for treating glioblastoma (GBM), which is a highly lethal brain tumor.

RNA nanoparticle therapies are being developed and will soon be tested in GBM patients, indicating a promising new approach to improve treatment outcomes for this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contemporary RNA Therapeutics for Glioblastoma. Melnick, K., Dastmalchi, F., Mitchell, D., et al.[2022]

Anti-gene vaccines targeting the growth factor IGF-I, specifically using antisense (AS) and triple helix (TH) approaches, have been shown to significantly increase median survival in glioblastoma (GBM) patients, with some patients surviving up to 2-3 years.

The TH vaccines demonstrated stronger immunogenicity and a more robust immune response compared to AS vaccines, leading to improved outcomes in terms of patient survival, with median survival extending to 17-18 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Gene IGF-I Vaccines in Cancer Gene Therapy: A Review of a Case of Glioblastoma. Trojan, A., Lone, YC., Briceno, I., et al.[2023]

Immunotherapy shows promise in treating glioblastoma by targeting cancer cells precisely while sparing healthy tissue, which could lead to better patient outcomes.

Various vaccination strategies, including peptide vaccines and dendritic cell vaccines, are being tested in clinical trials, indicating a growing interest in integrating these innovative therapies into standard treatment for glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine strategies for glioblastoma: progress and future directions. Jackson, C., Ruzevick, J., Brem, H., et al.[2021]

Recent advances in immunotherapy for glioblastomas (GBM) focus on developing neoantigen vaccines and immune modulators, which could improve treatment outcomes for this aggressive cancer.

Combining mRNA vaccines with personalized medicine approaches may enhance the effectiveness of therapies, particularly in overcoming the resistance of GBM to traditional immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced immunotherapies for glioblastoma: tumor neoantigen vaccines in combination with immunomodulators. Segura-Collar, B., Hiller-Vallina, S., de Dios, O., et al.[2023]

A vaccine using bone marrow-derived dendritic cells loaded with RNA from GL261 glioma cells successfully induced a specific T cell response and provided protection against brain tumors in mice.

The effectiveness of this vaccine was enhanced by adding recombinant interleukin-12, which suggests that combining immunotherapy with cytokines could improve treatment outcomes for intracranial malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dendritic cell vaccine induces protective immunity to intracranial growth of glioma. Insug, O., Ku, G., Ertl, HC., et al.[2021]

Dendritic cell (DC) vaccination has been shown to be safe and non-toxic in early phase trials for treating glioblastoma multiforme (GBM), suggesting a promising new immunotherapy approach.

Pre-clinical studies in mice demonstrated that DCs loaded with glioblastoma proteins significantly increased survival rates, supporting the potential for clinical trials in patients with GBM who do not respond to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cells pulsed with glioma lysates induce immunity against syngeneic intracranial gliomas and increase survival of tumor-bearing mice. Pellegatta, S., Poliani, PL., Corno, D., et al.[2006]

Dendritic cell (DC)-based vaccines pulsed with tumor extracts or RNA significantly enhanced G422-specific cytotoxic T lymphocyte (CTL) responses in a mouse model of glioblastoma, indicating a strong immune activation.

Vaccination with these pulsed DCs not only improved CTL responses but also significantly prolonged survival in mice with glioblastoma, suggesting that this approach could be an effective therapeutic strategy against gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of intracranial G422 glioblastoma with dendritic cells pulsed with tumor extract or RNA. Zhang, Z., Tang, LL., Zhan, RY., et al.[2018]

References

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

mRNA aggregates harness danger response for potent cancer immunotherapy. [2023]

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

Contemporary RNA Therapeutics for Glioblastoma. [2022]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Anti-Gene IGF-I Vaccines in Cancer Gene Therapy: A Review of a Case of Glioblastoma. [2023]

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

Vaccine strategies for glioblastoma: progress and future directions. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Advanced immunotherapies for glioblastoma: tumor neoantigen vaccines in combination with immunomodulators. [2023]

6. Greece pubmed.ncbi.nlm.nih.gov

A dendritic cell vaccine induces protective immunity to intracranial growth of glioma. [2021]

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

Dendritic cells pulsed with glioma lysates induce immunity against syngeneic intracranial gliomas and increase survival of tumor-bearing mice. [2006]

8. China pubmed.ncbi.nlm.nih.gov

Immunotherapy of intracranial G422 glioblastoma with dendritic cells pulsed with tumor extract or RNA. [2018]