RNA Lipid Particles Targeting Pediatric Recurrent Intracranial Malignancies and Other systEmic Solid Tumors

Summary

The Investigators have demonstrated in preclinical studies that RNA liposomes activate APCs, induce antigen-specific T cell immunity, and can supplant DCs in a cell therapy model for HGG and have shown feasibility and activity of this approach in preclinical models and in canine patients with a spontaneous malignant glioma. In one arm of this study, we will investigate the safety and immunologic activity of RNA-LP vaccines in pediatric patients with recurrent pHGG.

The investigators have also shown that intravenous administration of tumor mRNA loaded lipid particles (LPs) localizes primarily to lung, transfect antigen presenting cells (APCs) and lead to an activated T cell response for induction of anti-tumor immunity. In contrast to other formulations, RNA-LPs recruit multiple arms of the immune system (i.e. innate/adaptive), and remodel the systemic/intratumoral immune milieu, which remain potent barriers for vaccine, cellular, and checkpoint inhibiting immunotherapies. After only a single RNA-LP vaccine, the bulk of systemic and intratumoral dendritic cells (DCs) in mice display an activated phenotype; these activated DCs (harvested from tumors) expand antigen specific T cell immunity. In immunologically resistant pulmonary osteosacroma murine tumor models (i.e. K7M2), RNA-LPs induce robust anti-tumor efficacy in settings where immune checkpoint inhibitors (i.e. anti-PD-L1 therapy) do not confer therapeutic benefit. The investigators have already demonstrated safety of RNA-LPs in acute/chronic murine toxicity studies, and in client-owned canine trial.

In this study, we will investigate the manufacturing feasibility, safety and immunologic activity of RNA-LP vaccine in patients with recurrent pulmonary or unresectable osteosarcoma and recurrent pHGG.

Conditions

• Recurrent Pulmonary Osteosarcoma
• Recurrent High-grade Glioma

Interventions

BIOLOGICAL

pp65 RNA LP (DP1)

This is an off the shelf RNA-LP vaccine used to prime for the immune response while we produce the patient specific pp65/tumor mRNA RNA-LP (DP2)

BIOLOGICAL

pp65/tumor mRNA RNA-LP (DP2)

This is a patient specific RNA-LP vaccine generated from the patient's tumor RNA.

PROCEDURE

Surgical Biopsy/Resection

Eligible participants will be enrolled and undergo sterile collection of tumor material .

Sponsors & Collaborators

• The V Foundation for Cancer Research

  collaborator OTHER

• National Pediatric Cancer Foundation

  collaborator OTHER

• Alex's Lemonade Stand Foundation

  collaborator INDUSTRY

• The Osteosarcoma Institute

  collaborator UNKNOWN

• National Cancer Institute (NCI)

  collaborator NIH

• University of Florida

  lead OTHER

Principal Investigators

• John Ligon, MD · University of Florida

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

3 Years

Max Age

39 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-03-12

Primary Completion

2033-10-31

Completion

2035-10-31

FDA Drug

Yes

Countries

• United States

Study Locations