Abstract
IL-12 has demonstrated remarkable antitumor activity when used directly as a recombinant protein or when different viral or non-viral vectors transfer its genes. At enhancing tumor immunity, IL-12 acts as a bridge between innate and adaptive immune responses due to its ability to induce proliferation and activation of NK, NKT, and T cells. In addition, IL-12 inhibits tumor angiogenesis mainly through IFNγ-dependent production of the chemokine IP10. As a result, IL-12 can eliminate several types of tumors developed in rodents. Pre-clinical experience forecasted a quick and successful clinical translation, but the encouraging results observed in animals were not reproduced in patients. Moreover, unacceptable toxicity resulting from IFNγ overproduction was observed in 2 renal carcinoma patients included in a phase II clinical trial that consisted in systemic administration of rIL-12. As a consequence, development of IL-12 as an antitumor agent was temporarily halted while the high expectations raised among clinicians faded away. Gene transfer methods are designed to confine IL-12 production in the tumor environment preventing systemic toxicity. Tumor cells, dendritic cells, or autologous fibroblasts have been transfected with recombinant adenoviruses or retroviruses to secrete IL-12 locally, showing good efficacy and safety profiles. IL-12 combination with other immunotherapy approaches synergizes to achieve even better results. Encouraging pilot clinical results have been recently obtained from the first phase I trial studying adenovirus mediated in vivo gene transfer of IL-12 into lesions of advanced cancer patients. Further improvements will follow from: i) increases in the efficacy of gene transduction; ii) development of tumor specific promoters; iii) development of regulatable and long-term expression vectors and iv) combination with other immunological and non-immunological anticancer therapies.
Keywords: il-12, gene therapy, cancer, adenovirus, dendritic cells, mouse, clinical trials
Current Pharmaceutical Design
Title: Gene Therapy of Cancer with Interleukin-12
Volume: 9 Issue: 24
Author(s): Guillermo Mazzolini, Jesus Prieto and Ignacio Melero
Affiliation:
Keywords: il-12, gene therapy, cancer, adenovirus, dendritic cells, mouse, clinical trials
Abstract: IL-12 has demonstrated remarkable antitumor activity when used directly as a recombinant protein or when different viral or non-viral vectors transfer its genes. At enhancing tumor immunity, IL-12 acts as a bridge between innate and adaptive immune responses due to its ability to induce proliferation and activation of NK, NKT, and T cells. In addition, IL-12 inhibits tumor angiogenesis mainly through IFNγ-dependent production of the chemokine IP10. As a result, IL-12 can eliminate several types of tumors developed in rodents. Pre-clinical experience forecasted a quick and successful clinical translation, but the encouraging results observed in animals were not reproduced in patients. Moreover, unacceptable toxicity resulting from IFNγ overproduction was observed in 2 renal carcinoma patients included in a phase II clinical trial that consisted in systemic administration of rIL-12. As a consequence, development of IL-12 as an antitumor agent was temporarily halted while the high expectations raised among clinicians faded away. Gene transfer methods are designed to confine IL-12 production in the tumor environment preventing systemic toxicity. Tumor cells, dendritic cells, or autologous fibroblasts have been transfected with recombinant adenoviruses or retroviruses to secrete IL-12 locally, showing good efficacy and safety profiles. IL-12 combination with other immunotherapy approaches synergizes to achieve even better results. Encouraging pilot clinical results have been recently obtained from the first phase I trial studying adenovirus mediated in vivo gene transfer of IL-12 into lesions of advanced cancer patients. Further improvements will follow from: i) increases in the efficacy of gene transduction; ii) development of tumor specific promoters; iii) development of regulatable and long-term expression vectors and iv) combination with other immunological and non-immunological anticancer therapies.
Export Options
About this article
Cite this article as:
Mazzolini Guillermo, Prieto Jesus and Melero Ignacio, Gene Therapy of Cancer with Interleukin-12, Current Pharmaceutical Design 2003; 9 (24) . https://dx.doi.org/10.2174/1381612033454261
DOI https://dx.doi.org/10.2174/1381612033454261 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- 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
-
Targeting the Ubiquitin Proteasome System: Beyond Proteasome Inhibition
Current Pharmaceutical Design A Synopsis on the Role of Human Papilloma Virus Infection in Cervical Cancer
Current Drug Metabolism Peptide Targeted Copper-64 Radiopharmaceuticals
Current Topics in Medicinal Chemistry Strategies to Increase the Oral Bioavailability of Nucleoside Analogs
Current Medicinal Chemistry Anti-IL-13 in Inflammatory Bowel Disease: From the Bench to the Bedside
Current Drug Targets Delineation of Current Development of Antimitotic Compounds Targeting Cytoskeletal Protein Tubulin and Microtubule in the Cancer Therapy
Current Chemical Biology Wnt / β-Catenin Signaling Pathway as Novel Cancer Drug Targets
Current Cancer Drug Targets Jun Dimerization Protein 2 in Oxygen Restriction; Control of Senescence
Current Pharmaceutical Design Cancer-Type Organic Anion Transporting Polypeptide 1B3: Current Knowledge of the Gene Structure, Expression Profile, Functional Implications and Future Perspectives
Current Drug Metabolism Toxicities of Targeted Agents in Advanced Renal Cell Carcinoma
Current Clinical Pharmacology Paraneoplastic Neurological Syndromes - Diagnosis and Management
Current Pharmaceutical Design Malignancy in Common Variable Immune Deficiency: Report of Two Rare Cases of Gastrointestinal Malignancy and a Review of the Literature
Cardiovascular & Hematological Disorders-Drug Targets Pharmacogenomics – Implications in the Development of HIV-Associated Brain Disease
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Targeting the Tumor Proteasome as a Mechanism to Control the Synthesis and Bioactivity of Matrix Macromolecules
Current Molecular Medicine Marine Natural Products and Related Compounds as Anticancer Agents: an Overview of their Clinical Status
Anti-Cancer Agents in Medicinal Chemistry Recent Clinical Trials of mTOR-Targeted Cancer Therapies
Reviews on Recent Clinical Trials Therapeutic Strategies to Target Multiple Kinases in Glioblastoma
Anti-Cancer Agents in Medicinal Chemistry Wnt Signaling in Renal Cancer
Current Drug Targets BMPS and Liver: More Questions than Answers
Current Pharmaceutical Design Recent Advances in Characterizing Natural Products that Regulate Autophagy
Anti-Cancer Agents in Medicinal Chemistry