title: A Phase l Study of a Tumor-targeted Systemic Nanodelivery System, SGT-94, in Genitourinary Cancers.
abstract: Gene therapy development has been limited by our inability to target multifocal cancer with systemic delivery. We developed a systemically administered, tumor-targeted liposomal nanodelivery complex (SGT-94) carrying a plasmid encoding RB94, a truncated form of the RB gene. In preclinical studies, RB94 showed marked cytotoxicity against tumor but not normal cells. SGT-94 was administered intravenously in a first-in-man study in metastatic genitourinary cancer. Minimal side effects were observed; dose-limiting toxicity (DLT) has not been reached in 11 evaluable patients. There was evidence of clinical activity at the 2.4 mg dose with one complete remission (CR) and one partial remission (PR). The patient in CR was retreated upon progression and had a second PR. Furthermore, there was tumor-specific targeting of the SGT-94 complex. One patient had wedge resections of two lung metastases which demonstrated RB94 expression at the DNA level by polymerase chain reaction (PCR) and at the protein level by Western blotting, with no RB94 present in normal contiguous lung. In conclusion, systemically delivered SGT-94 showed evidence of selective tumor targeting and was well tolerated with evidence of clinical activity. Additional studies are warranted to explore the activity of this drug as a single agent and in combination therapy.
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Arlene
authors.initials: A
authors.lastname: Siefker-Radtke
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xin-Qiao
authors.initials: XQ
authors.lastname: Zhang
authors.affiliation: Department of Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Guo
authors.affiliation: Department of Biostatistics, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Oncology, Georgetown University Medical Center, Washington, District of Columbia, USA.
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Pirollo
authors.affiliation: Department of Interventional Radiology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Sharjeel
authors.initials: S
authors.lastname: Sabir
authors.affiliation: SynerGene Therapeutics, Inc., Potomac, Maryland, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Leung
authors.affiliation: SynerGene Therapeutics, Inc., Potomac, Maryland, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Leong-Wu
authors.affiliation: SynerGene Therapeutics, Inc., Potomac, Maryland, USA.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Ling
authors.affiliation: Department of Oncology, Georgetown University Medical Center, Washington, District of Columbia, USA.|SynerGene Therapeutics, Inc., Potomac, Maryland, USA.
authors.forename: Esther H
authors.initials: EH
authors.lastname: Chang
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Randall E
authors.initials: RE
authors.lastname: Millikan
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Benedict
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods; D006801:Humans; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D050997:Nanomedicine / Q000379:methods; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010957:Plasmids / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics*; D011990:Receptors, Transferrin / Q000276:immunology; D016160:Retinoblastoma Protein / Q000235:genetics; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology; D014057:Tomography, X-Ray Computed; D019076:Transgenes; D016896:Treatment Outcome; D014565:Urogenital Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy*
chemical_list: D008081:Liposomes; D011990:Receptors, Transferrin; D016160:Retinoblastoma Protein; D057127:Single-Chain Antibodies