Phase I study of a systemically delivered p53 nanoparticle in advanced solid tumors

Area of Science:

• Oncology
• Nanomedicine
• Gene Therapy

Background:

• Selective delivery of therapeutics to tumors is crucial for effective cancer treatment.
• Loss of p53 suppressor function is common in human cancers and essential for tumor growth.
• A liposomal nanodelivery complex (scL) using anti-transferrin receptor (TfR) scFv has been developed for targeted delivery.

Purpose of the Study:

• To evaluate the safety and efficacy of SGT-53, a scL nanocomplex designed to restore p53 tumor suppressor gene function, in a first-in-man Phase I clinical trial.
• To assess the targeted delivery of SGT-53 to primary and metastatic tumors.

Main Methods:

• A Phase I clinical trial was conducted involving patients with advanced solid tumors.
• Patients received systemic delivery of the SGT-53 nanocomplex.
• Tumor accumulation of the transgene and side effects were monitored.

Main Results:

• SGT-53 was well tolerated with minimal side effects in patients with advanced solid tumors.
• The majority of patients experienced stable disease, and one patient's tumor became resectable.
• Dose-dependent accumulation of the transgene was observed in metastatic tumors but not in normal skin tissue.

Conclusions:

• Systemically delivered SGT-53 is well tolerated and demonstrates anticancer activity.
• SGT-53 shows evidence of targeted delivery to metastatic lesions, supporting its potential as a novel cancer therapeutic.