← Back to Search
Tumor-targeted P53-gene Therapy Enhances The Efficacy Of Conventional Chemo/radiotherapy.
L. Xu, K. Pirollo, E. Chang
Published 2001 · Medicine
Download PDFAnalyze on Scholarcy
A long-standing goal in gene therapy for cancer is a stable, low toxic, systemic gene delivery system that selectively targets tumor cells, including metastatic disease. Progress has been made toward developing non-viral, pharmaceutical formulations of genes for in vivo human therapy, particularly cationic liposome-mediated gene transfer systems. Ligand-directed tumor targeting of cationic liposome-DNA complexes (lipoplexes) is showing promise for targeted gene delivery and systemic gene therapy. Lipoplexes directed by ligands such as folate, transferrin or anti-transferrin receptor scFv, showed tumor-targeted gene delivery and expression in human breast, prostate, head and neck cancers. The two elements, ligand/receptor and liposome composition, work together to realize the goal of functional tumor targeting of gene therapeutics. The tumor suppressor gene, p53, has been shown to be involved in the control of DNA damage-induced apoptosis. Loss or malfunction of this p53-mediated apoptotic pathway has been proposed as one mechanism by which tumors become resistant to chemotherapy or radiation. The systemically delivered ligand-liposome-p53 gene therapeutics resulted in efficient expression of functional wild-type p53, sensitizing the tumors to chemotherapy and radiotherapy. This is a novel strategy combining current molecular medicine with conventional chemotherapy and radiotherapy for the treatment of cancer. The systemic delivery of normal tumor suppressor gene p53 by a non-viral, tumor-targeted delivery system as a new therapeutic intervention has the potential to critically impact the clinical management of cancer.
This paper references
Cationic liposomes as gene transfer vectors: barriers to successful application in gene therapy.
S. Simões (1999)
Transferrin-liposome-mediated systemic p53 gene therapy in combination with radiation results in regression of human head and neck cancer xenografts.
L. Xu (1999)
Non-viral gene delivery for p53.
K. Pirollo (2000)
Gene therapy with p53 and a fragment of thrombospondin I inhibits human breast cancer in vivo.
M. Xu (1998)
Important advances in oncology
V. Devita (1991)
Structure of DNA-Cationic Liposome Complexes: DNA Intercalation in Multilamellar Membranes in Distinct Interhelical Packing Regimes
J. Rädler (1997)
GD2‐mediated melanoma cell targeting and cytotoxicity of liposome‐entrapped fenretinide
G. Pagnan (1999)
Stabilized plasmid-lipid particles: factors influencing plasmid entrapment and transfection properties.
K. Mok (1999)
Clinical implications of the p53 gene.
D. Sidransky (1996)
Cloning and expression of a chimeric antibody directed against the human transferrin receptor.
H. Hoogenboom (1990)
The transferrin receptor: its diagnostic value and its potential as therapeutic target.
K. Thorstensen (1993)
Signaling networks and cell cycle control : the molecular basis of cancer and other diseases
J. S. Gutkind (2000)
Breast Carcinoma and the Role of Iron Metabolism
R. L. Elliott (1993)
Stabilized plasmid-lipid particles: construction and characterization
J J Wheeler (1999)
Debates, divisions, and decisions: recombinant DNA advisory committee (RAC) authorization of the first human gene transfer experiments.
I. H. Carmen (1992)
Delivery of c-myb Antisense Oligodeoxynucleotides to Human Neuroblastoma Cells Via Disialoganglioside GD2-Targeted Immunoliposomes: Antitumor Effects.
G. Pagnan (2000)
Cox-2, iNOS and p53 as play-makers of tumor angiogenesis (review).
V. Chiarugi (1998)
Cationic lipid binding to DNA: characterization of complex formation.
F. Wong (1996)
Anti-HER2 immunoliposomes for targeted therapy of human tumors.
J. Park (1997)
Systemic gene therapy with p53 reduces growth and metastases of a malignant human breast cancer in nude mice.
L. Lesoon-Wood (1995)
Improved DNA: liposome complexes for increased systemic delivery and gene expression
Nancy Smyth Templeton (1997)
Signaling Networks and Cell Cycle Control
J. S. Gutkind (2000)
Cationic lipid-mediated gene transfer: current concepts.
P. R. Clark (1999)
Targetability of novel immunoliposomes modified with amphipathic poly(ethylene glycol)s conjugated at their distal terminals to monoclonal antibodies.
K. Maruyama (1995)
Receptor blockade with monoclomal antibodies as anti-cancer therapy
J. Baselga (1994)
Preparation of liposomes
G. Gregoriadis (1984)
p53 and response to chemotherapy and radiotherapy.
H. Ruley (1996)
Systemic gene therapy with p53 inhibits breast cancer: recent advances and therapeutic implications.
Chen Qr (1998)
Effective treatment of early endobronchial cancer with regional administration of liposome-p53 complexes.
Y. Zou (1998)
Anti‐HER2 Immunoliposomes for Targeted Drug Delivery
K. Hong (1999)
Parenteral gene therapy with p53 inhibits human breast tumors in vivo through a bystander mechanism without evidence of toxicity.
M. Xu (1997)
Delivery of liposomes into cultured KB cells via folate receptor-mediated endocytosis.
R. Lee (1994)
Transferrin receptor in oral tumors.
T. Miyamoto (1994)
Selective transfer of a lipophilic prodrug of 5-fluorodeoxyuridine from immunoliposomes to colon cancer cells.
G. Koning (1999)
Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure.
P. Felgner (1987)
Targeted p53 Gene Therapy-Mediated Radiosensitization and Chemosensitization
E. Chang (2000)
Pharmacokinetics, tissue distribution, and expression efficiency of plasmid [33P]DNA following intravenous administration of DNA/cationic lipid complexes in mice: use of a novel radionuclide approach.
G. Osaka (1996)
Receptor ligand-facilitated gene transfer: enhancement of liposome-mediated gene transfer and expression by transferrin.
P. W. Cheng (1996)
Progress in Gene Delivery Research and Development
P. Felgner (1999)
The Perplexing Delivery Mechanism of Lipoplexes
L. Barron (1999)
Stabilization of cationic liposome‐plasmid DNA complexes by polyamines and poly(ethylene glycol)‐phospholipid conjugates for efficient in vivo gene delivery
K. Hong (1997)
Folate receptor of human mammary adenocarcinoma
J. Holm (1994)
Folate-targeted, Anionic Liposome-entrapped Polylysine-condensed DNA for Tumor Cell-specific Gene Transfer (*)
R. Lee (1996)
Liposomes : a practical approach
R. New (1990)
Ligand—Polycation Conjugates for Receptor-Targeted Gene Transfer
E. Wagner (1999)
Elevated transferrin receptor content in human prostate cancer cell lines assessed in vitro and in vivo.
H. N. Keer (1990)
Tumor-selective radiopharmaceutical targeting via receptor-mediated endocytosis of gallium-67-deferoxamine-folate.
C. Mathias (1996)
The p53 gene as a modifier of intrinsic radiosensitivity: implications for radiotherapy.
R. Bristow (1996)
Transferrin-liposome-mediated p53 sensitization of squamous cell carcinoma of the head and neck to radiation in vitro.
L. Xu (1997)
This paper is referenced by
Single-fraction γ-60Co radiation induces apoptosis in cultured rat C6 cells
Jie-fang Bian (2012)
"Combo" nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy.
J. Kemp (2016)
Characterization and Use of Folate Receptor Isoforms for Targeting of Epithelial and Myeloid Cells
Sreya Biswas (2016)
Targeted drug delivery via folate receptors
X. Zhao (2008)
Development of Nonviral DNA Delivery Systems
H. Hofland (2004)
New bifunctional-pullulan-based micelles with good biocompatibility for efficient co-delivery of cancer-suppressing p53 gene and doxorubicin to cancer cells
Lili Chen (2015)
Liposomes Conjugated with a Pilot Molecule
Kosuke Shimizu (2019)
Folate receptor-targeted immunotherapy of cancer: mechanism and therapeutic potential.
Y. Lu (2004)
Animal models and therapeutic molecular targets of cancer: utility and limitations
M. Cekanova (2014)
Folate Receptor Targeting Probes for Two-Photon Fluorescence Bioimaging
A. Morales (2010)
Combination of doxorubicin-based chemotherapy and polyethylenimine/p53 gene therapy for the treatment of lung cancer using porous PLGA microparticles.
Xiaozheng Shi (2014)
MicroRNA100 inhibits self-renewal of breast cancer stem-like cells and breast tumor development.
L. Deng (2014)
Folic acid-conjugated BSA nanocapsule (n-BSA–FA) for cancer targeted radiotherapy and imaging
Sheng Liang (2015)
The present and future of nanotechnology in human health care.
S. Sahoo (2007)
Development of a transferrin receptor-targeting HVJ-E vector.
Takashi Shimbo (2007)
Use of p53 for therapy of human cancer
V. P. Almazov (2007)
Systemic tumor-targeted gene delivery by anti-transferrin receptor scFv-immunoliposomes.
L. Xu (2002)
Lipid-based Nanoparticles for Nucleic Acid Delivery
Weijun Li (2006)
Phase I study of a systemically delivered p53 nanoparticle in advanced solid tumors.
N. Senzer (2013)
Novel luminescent silica nanoparticles (LSN): p53 gene delivery system in breast cancer in vitro and in vivo
C. Rejeeth (2016)
Mechanisms of TfR-mediated transcytosis and sorting in epithelial cells and applications toward drug delivery.
A. Widera (2003)
Development of microRNA-145 for therapeutic application in breast cancer.
S. Kim (2011)
Radiation improves gene delivery by a novel transferrin-lipoplex nanoparticle selectively in cancer cells
R. Abela (2008)
Conjugating folic acid to gold nanoparticles through glutathione for targeting and detecting cancer cells.
Zhaowu Zhang (2010)
Targeted delivery of antisense oligodeoxynucleotides to folate receptor-overexpressing tumor cells.
L. Yang (2004)
Enhanced transfection efficiency of a systemically delivered tumor-targeting immunolipoplex by inclusion of a pH-sensitive histidylated oligolysine peptide.
Wei Yu (2004)
Pyridinium Bisretinoids: Synthesis and Photoactivated Cytotoxicity
J. Gao (2007)
MicroRNAs, stem cells and cancer stem cells.
M. Garg (2012)
Nanoparticle-mediated p53 gene therapy for tumor inhibition
B. Sharma (2010)
Radiosensitization by Gene Therapy
S. Chmura (2005)
The p53 protein family and radiation sensitivity: Yes or no?
Andrew R. Cuddihy (2004)
Development of purification methods for tumor targeted polyplexes applied in vivo
Julia Fahrmeir (2007)See more