Abstract
Effective delivery still remains a major hurdle in the development of gene based therapies. While technological advances have occurred that have improved delivery in general, there is still a need for controlled delivery in order to achieve therapeutic effects. Gene electrotransfer (GET) can be utilized to accomplish this. Careful selection of parameters used for delivery such as amplitude, duration and number of pulses as well as plasmid construct can be manipulated in order to achieve appropriate levels of local expression. Previously we have shown that direct delivery of the therapeutic cytokine, interleukin 12 (IL-12), to tumors using electrotransfer can generate local and systemic anti-tumor effects in pre-clinical and clinical studies. Using this model we hypothesized that modulating local gene expression using GET can affect therapeutic outcome. To test this, we used multiple GET protocols and plasmids to achieve varying levels of local IL-12 expression. We found that high local gene expression did not give rise to a better therapeutic outcome. This suggests the level and possibly the duration of gene expression are important in mediating the host immune response against melanoma. These data also emphasize the importance of considering the desired immune outcome of the therapy when selecting parameters for GET.
Keywords: Cytokine, electrotransfer, gene therapy, immunotherapy, interleukin-12, melanoma.
Current Gene Therapy
Title:Controlled Gene Delivery Can Enhance Therapeutic Outcome for Cancer Immune Therapy for Melanoma
Volume: 15 Issue: 1
Author(s): Shawna A. Shirley, Cathryn G. Lundberg, Fanying Li, Niculina Burcus and Richard Heller
Affiliation:
Keywords: Cytokine, electrotransfer, gene therapy, immunotherapy, interleukin-12, melanoma.
Abstract: Effective delivery still remains a major hurdle in the development of gene based therapies. While technological advances have occurred that have improved delivery in general, there is still a need for controlled delivery in order to achieve therapeutic effects. Gene electrotransfer (GET) can be utilized to accomplish this. Careful selection of parameters used for delivery such as amplitude, duration and number of pulses as well as plasmid construct can be manipulated in order to achieve appropriate levels of local expression. Previously we have shown that direct delivery of the therapeutic cytokine, interleukin 12 (IL-12), to tumors using electrotransfer can generate local and systemic anti-tumor effects in pre-clinical and clinical studies. Using this model we hypothesized that modulating local gene expression using GET can affect therapeutic outcome. To test this, we used multiple GET protocols and plasmids to achieve varying levels of local IL-12 expression. We found that high local gene expression did not give rise to a better therapeutic outcome. This suggests the level and possibly the duration of gene expression are important in mediating the host immune response against melanoma. These data also emphasize the importance of considering the desired immune outcome of the therapy when selecting parameters for GET.
Export Options
About this article
Cite this article as:
Shirley A. Shawna, Lundberg G. Cathryn, Li Fanying, Burcus Niculina and Heller Richard, Controlled Gene Delivery Can Enhance Therapeutic Outcome for Cancer Immune Therapy for Melanoma, Current Gene Therapy 2015; 15 (1) . https://dx.doi.org/10.2174/1566523214666141121111630
DOI https://dx.doi.org/10.2174/1566523214666141121111630 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
Call for Papers in Thematic Issues
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)
Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
G Protein-Coupled Receptors and their Signaling Pathways: Classical Therapeutical Targets Susceptible to Novel Therapeutic Concepts
Current Pharmaceutical Design Quinazolines as Apoptosis Inducers and Inhibitors: A Review of Patent Literature
Recent Patents on Anti-Cancer Drug Discovery Natural Products as Exquisitely Potent Cytotoxic Payloads for Antibody- Drug Conjugates
Current Topics in Medicinal Chemistry Recent Trends in the Pharmacological Activity of Isoprenyl Phenolics
Current Medicinal Chemistry New Antitumour Natural Products from Marine Red Algae: Covering the Period from 2003 to 2012
Mini-Reviews in Medicinal Chemistry Sorafenib (BAY 43-9006): Review of Clinical Development
Current Clinical Pharmacology IGF Signaling Pathway as a Selective Target of Familial Breast Cancer Therapy
Current Molecular Medicine Novel Nanolipoidal Systems for the Management of Skin Cancer
Recent Patents on Drug Delivery & Formulation Pharmacological Inhibition of the Bcl-2 Family of Apoptosis Regulators as Cancer Therapy
Current Molecular Pharmacology Natural Bio-Drugs as Matrix Metalloproteinase Inhibitors: New Perspectives on the Horizon?
Recent Patents on Anti-Cancer Drug Discovery Contribution of Platelet-Derived CD40 Ligand to Inflammation, Thrombosis and Neoangiogenesis
Current Medicinal Chemistry Anti-Tumor Effects of Osthole on Different Malignant Tissues: A Review of Molecular Mechanisms
Anti-Cancer Agents in Medicinal Chemistry Momordica balsamina: A Medicinal and Neutraceutical Plant for Health Care Management
Current Pharmaceutical Biotechnology Abnormal Choline Phospholipid Metabolism in Breast and Ovary Cancer:Molecular Bases for Noninvasive Imaging Approaches
Current Medical Imaging Data-driven Approach to Detect and Predict Adverse Drug Reactions
Current Pharmaceutical Design Drug-Mediated Targeted Disruption of Multiple Protein Activities Through Functional Inhibition of the Hsp90 Chaperone Complex
Current Medicinal Chemistry Ultrasonic and Microwave Assisted Synthesis of Nitrogen-Containing Derivatives of Juglone as Potential Antibacterial Agents
Letters in Organic Chemistry Lycopene Modulation of Molecular Targets Affected by Smoking Exposure
Current Cancer Drug Targets Understanding the Molecular Properties and Metabolism of Top Prescribed Drugs
Current Topics in Medicinal Chemistry Targeting Cell Death in Tumors by Activating Caspases
Current Cancer Drug Targets