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Mol Ther. 2013 May;21(5):1096-103. doi: 10.1038/mt.2013.32. Epub 2013 Apr 23.

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

Author information

1
Mary Crowley Cancer Research Centers, Dallas, Texas 75201, USA.

Abstract

Selective delivery of therapeutic molecules to primary and metastatic tumors is optimal for effective cancer therapy. A liposomal nanodelivery complex (scL) for systemic, tumor-targeting delivery of anticancer therapeutics has been developed. scL employs an anti-transferrin receptor (TfR), scFv as the targeting molecule. Loss of p53 suppressor function, through mutations or inactivation of the p53 pathway, is present in most human cancers. Rather than being transiently permissive for tumor initiation, persistence of p53 dysfunction is a continuing requirement for maintaining tumor growth. Herein, we report results of a first-in-man Phase I clinical trial of restoration of the normal human tumor suppressor gene p53 using the scL nanocomplex (SGT-53). Minimal side effects were observed in this trial in patients with advanced solid tumors. Furthermore, the majority of patients demonstrated stable disease. One patient with adenoid cystic carcinoma had his status changed from unresectable to resectable after one treatment cycle. More significantly, we observed an accumulation of the transgene in metastatic tumors, but not in normal skin tissue, in a dose-related manner. These results show not only that systemically delivered SGT-53 is well tolerated and exhibits anticancer activity, but also supply evidence of targeted tumor delivery of SGT-53 to metastatic lesions.

PMID:
23609015
PMCID:
PMC3666630
DOI:
10.1038/mt.2013.32
[Indexed for MEDLINE]
Free PMC Article

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