RNA-Lipid Particle Vaccines for Recurrent Glioblastoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of Florida
Must not be taking: Bevacizumab, Live vaccines
Disqualifiers: Active infection, Uncontrolled seizures, AIDS, others
No Placebo Group
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.
12345Is 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.
12367How 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.
23568Eligibility 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.
+14 more
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.
+3 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Arm 2: pp65 RNA-LPs (DP1) after biopsyExperimental Treatment2 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 biopsyExperimental Treatment2 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).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UF HealthGainesville, FL
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Who Is Running the Clinical Trial?
University of FloridaLead Sponsor
National Cancer Institute (NCI)Collaborator
References
mRNA aggregates harness danger response for potent cancer immunotherapy. [2023]Messenger RNA (mRNA) has emerged as a remarkable tool for COVID-19 prevention but its use for induction of therapeutic cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Herein, we develop a facile approach for substantially enhancing immunogenicity of tumor-derived mRNA in lipid-particle (LP) delivery systems. By using mRNA as a molecular bridge with ultrapure liposomes and foregoing helper lipids, we promote the formation of 'onion-like' multi-lamellar RNA-LP aggregates (LPA). Intravenous administration of RNA-LPAs mimics infectious emboli and elicits massive DC/T cell mobilization into lymphoid tissues provoking cancer immunogenicity and mediating rejection of both early and late-stage murine tumor models. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for toll-like receptor engagement, RNA-LPAs stimulate intracellular pathogen recognition receptors (RIG-I) and reprogram the TME thus enabling therapeutic T cell activity. RNA-LPAs were safe in acute/chronic murine GLP toxicology studies and immunologically active in client-owned canines with terminal gliomas. In an early phase first-in-human trial for patients with glioblastoma, we show that RNA-LPAs encoding for tumor-associated antigens elicit rapid induction of pro-inflammatory cytokines, mobilization/activation of monocytes and lymphocytes, and expansion of antigen-specific T cell immunity. These data support the use of RNA-LPAs as novel tools to elicit and sustain immune responses against poorly immunogenic tumors.
Contemporary RNA Therapeutics for Glioblastoma. [2022]Glioblastoma (GBM) is the most common primary brain tumor in adults and is universally lethal with a median survival of less than two years with standard therapy. RNA-based immunotherapies have significant potential to establish a durable treatment response for malignant brain tumors including GBM. RNA offers clear advantages over antigen-focused approaches but cannot often be directly administered due to biological instability. This review will focus on utilization of RNA dendritic cell vaccines and RNA nanoparticle therapies in the treatment of GBM. RNA-pulsed dendritic cell vaccines have been shown to be safe in a small phase I clinical trial and RNA-loaded nanoparticle vaccines will soon be underway in GBM patients (NCT04573140).
Anti-Gene IGF-I Vaccines in Cancer Gene Therapy: A Review of a Case of Glioblastoma. [2023]Vaccines for the deadliest brain tumor - glioblastoma (GBM) - are generally based on targeting growth factors or their receptors, often using antibodies. The vaccines described in the review were prepared to suppress the principal cancer growth factor - IGF-I, using anti-gene approaches either of antisense (AS) or of triple helix (TH) type. Our objective was to increase the median survival of patients treated with AS and TH cell vaccines.
Vaccine strategies for glioblastoma: progress and future directions. [2021]Recent advances in glioblastoma therapy have led to optimism that more effective therapies will improve outcomes. Immunotherapy is a promising approach that has demonstrated the potential to eradicate cancer cells with cellular-level accuracy while minimizing damage to surrounding healthy tissue. Several vaccination strategies have been evaluated for activity against glioblastoma in clinical trials. These include peptide vaccines, polyvalent dendritic cell vaccines, heat shock protein vaccines and adoptive immunotherapy. In this review, we highlight clinical trials representative of each of these approaches and discuss strategies for integrating these therapies into routine patient care.
Advanced immunotherapies for glioblastoma: tumor neoantigen vaccines in combination with immunomodulators. [2023]Glial-origin brain tumors, including glioblastomas (GBM), have one of the worst prognoses due to their rapid and fatal progression. From an oncological point of view, advances in complete surgical resection fail to eliminate the entire tumor and the remaining cells allow a rapid recurrence, which does not respond to traditional therapeutic treatments. Here, we have reviewed new immunotherapy strategies in association with the knowledge of the immune micro-environment. To understand the best lines for the future, we address the advances in the design of neoantigen vaccines and possible new immune modulators. Recently, the efficacy and availability of vaccine development with different formulations, especially liposome plus mRNA vaccines, has been observed. We believe that the application of new strategies used with mRNA vaccines in combination with personalized medicine (guided by different omic's strategies) could give good results in glioma therapy. In addition, a large part of the possible advances in new immunotherapy strategies focused on GBM may be key improving current therapies of immune checkpoint inhibitors (ICI), given the fact that this type of tumor has been highly refractory to ICI.
A dendritic cell vaccine induces protective immunity to intracranial growth of glioma. [2021]The central nervous system is an immunologically privileged site hidden behind the blood brain barrier. Nevertheless, immune effector cells induced peripherally can be recruited into the central nervous system. Active immunotherapy of intracranial malignancies is thus potentially feasible. In this study we describe a vaccine regimen, based on bone marrow-derived dendritic cells pulsed with the RNA derived from GL261 glioma cells that induces a specific T cell response and protection against intracerebrally implanted GL261 tumors. Immunohistochemical analysis of brain tumors from vaccinated mice was characterized by pronounced intratumoral infiltrates predominantly of CD4+ as well as CD8+ T cells. The efficacy of the vaccine was improved further by administration of recombinant interleukin-12 into the vaccine regimen.
Dendritic cells pulsed with glioma lysates induce immunity against syngeneic intracranial gliomas and increase survival of tumor-bearing mice. [2006]In recent years, the use of dendritic cells (DC), the most powerful antigen presenting cells, has been proposed for the creation of vaccines against gliomas. This approach has been demonstrated to be safe and non-toxic in phase I or I-II trials (2, 3). Immunotherapy plays a central role in the search for new treatments for glioblastoma multiforme (GBM). In particular, several phase I studies have been performed using DC pulsed by GBM proteins as a vaccine for patients with relapsing GBM. The studies demonstrated that DC vaccination is safe and may produce a significant increase in overall survival. As the first step in the preparation of appropriate conditions for a clinical evaluation in Italy, we have performed pre-clinical experiments on immune-competent mice injected intra-cerebrally with syngeneic GL261GBM cells and treated subcutaneously and intra-tumorally with DC loaded with a GL261 homogenate. These results show that vaccination with DC pulsed with a tumor lysate increases considerably survival in mice bearing intracranial glioblastomas and supports the development of DC-based clinical trials for patients with glioblastomas that do not respond to standard therapies.
Immunotherapy of intracranial G422 glioblastoma with dendritic cells pulsed with tumor extract or RNA. [2018]To investigate the anti-tumor efficacy of dendritic cell (DC)-based vaccines pulsed with tumor extracts or RNA in a mouse model of intracranial G422 glioblastoma.