Abstract
Vaccines against cancers have not been as effective as vaccines against infectious diseases. However, recent studies have advanced our understanding of the stages of tumor cell development and of mechanisms of immune surveillance, immune suppression, and of tumor escape from the immune system. The development of animal models that mimic development of human cancers has helped advance the understanding of these processes and is aiding the development of greatly improved vaccines. Here we review the recent progress in developing vaccines and prophylactic approaches for pancreatic and colon cancers. Improved understanding of the expression of various oncogenes and tumor-associated antigens helps in selecting antigenic targets for stage-specific immune prevention. Identification of the earliest alterations in precancerous lesions and selection of epitopes unique to the aberrant cells and capable of triggering strong cytotoxic and helper T cell responses may aid the development of safe and effective vaccines for use in those at high risk of progressing to invasive cancers. The responses can be enhanced with carefully selected adjuvants to boost immunity and by selecting epitopes that are expressed on dendritic cells, thereby promoting T cell responses. Tumor resistance via loss of the targeted antigen can be mitigated by inclusion of multiple tumor epitopes in vaccine constructs. Tumor immune escape can be diminished by targeting various immunosuppressive mechanisms used by different tumors, such as tumor production of immunosuppressive cytokines (e.g., interleukin 10, and Transforming Growth Factor-beta, which can promote activity of immunosuppressive regulatory T cells), or by inhibiting production of inflammatory prostanoids with combined cyclooxygenase/lipoxygenase inhibitors. Finally, prevention of many cancers may be enhanced by carefully selecting and scheduling of vaccine administration in combination with other chemotherapeutic or chemopreventive agents. Preclinical and early clinical trials incorporating these principles are discussed.
Keywords: Colon cancer, pancreatic cancer, prophylactic vaccines, tumor-associated antigens, oncoproteins
Current Medicinal Chemistry
Title:Prophylactic Vaccine Approach for Colon and Pancreatic Cancers: Present and Future
Volume: 19 Issue: 22
Author(s): N. B. Janakiram, A. Mohammed, M. S. Bronze and C. V. Rao
Affiliation:
Keywords: Colon cancer, pancreatic cancer, prophylactic vaccines, tumor-associated antigens, oncoproteins
Abstract: Vaccines against cancers have not been as effective as vaccines against infectious diseases. However, recent studies have advanced our understanding of the stages of tumor cell development and of mechanisms of immune surveillance, immune suppression, and of tumor escape from the immune system. The development of animal models that mimic development of human cancers has helped advance the understanding of these processes and is aiding the development of greatly improved vaccines. Here we review the recent progress in developing vaccines and prophylactic approaches for pancreatic and colon cancers. Improved understanding of the expression of various oncogenes and tumor-associated antigens helps in selecting antigenic targets for stage-specific immune prevention. Identification of the earliest alterations in precancerous lesions and selection of epitopes unique to the aberrant cells and capable of triggering strong cytotoxic and helper T cell responses may aid the development of safe and effective vaccines for use in those at high risk of progressing to invasive cancers. The responses can be enhanced with carefully selected adjuvants to boost immunity and by selecting epitopes that are expressed on dendritic cells, thereby promoting T cell responses. Tumor resistance via loss of the targeted antigen can be mitigated by inclusion of multiple tumor epitopes in vaccine constructs. Tumor immune escape can be diminished by targeting various immunosuppressive mechanisms used by different tumors, such as tumor production of immunosuppressive cytokines (e.g., interleukin 10, and Transforming Growth Factor-beta, which can promote activity of immunosuppressive regulatory T cells), or by inhibiting production of inflammatory prostanoids with combined cyclooxygenase/lipoxygenase inhibitors. Finally, prevention of many cancers may be enhanced by carefully selecting and scheduling of vaccine administration in combination with other chemotherapeutic or chemopreventive agents. Preclinical and early clinical trials incorporating these principles are discussed.
Export Options
About this article
Cite this article as:
B. Janakiram N., Mohammed A., S. Bronze M. and V. Rao C., Prophylactic Vaccine Approach for Colon and Pancreatic Cancers: Present and Future, Current Medicinal Chemistry 2012; 19 (22) . https://dx.doi.org/10.2174/092986712801661022
DOI https://dx.doi.org/10.2174/092986712801661022 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Rational Basis for Nutraceuticals in the Treatment of Glaucoma
Current Neuropharmacology Morphological and Molecular Changes of the Myocardium After Left Ventricular Mechanical Support
Current Cardiology Reviews Depression in Coronary Heart Disease Patients: Etiological and Screening Issues
Current Psychiatry Reviews Editorial [Hot topic: The Inflammation Paradigm in Cardiovascular Disease (Guest Editor: Guha Krishnaswamy)]
Cardiovascular & Hematological Disorders-Drug Targets Application of Nanomedicine in Cardiovascular Diseases and Stroke
Current Pharmaceutical Design Virus-Associated Vasculitides: An Update
Current Immunology Reviews (Discontinued) Mechanisms of Fetal and Neonatal Renal Impairment by Pharmacologic Inhibition of Angiotensin
Current Medicinal Chemistry Disturbed Tryptophan Metabolism in Cardiovascular Disease
Current Medicinal Chemistry The Role of Fibrate Treatment in Dyslipidemia: An Overview
Current Pharmaceutical Design Resistant Hypertension in the Elderly-Second Line Treatments: Aldosterone Antagonists, Central Alpha-Agonist Agents, Alpha-Adrenergic Receptor Blockers, Direct Vasodilators, and Exogenous Nitric Oxide Donors
Cardiovascular & Hematological Agents in Medicinal Chemistry The Emerging Role of microRNA in Stroke
Current Topics in Medicinal Chemistry Exosomes: A Role for Naturally Occurring Nanovesicles in Cancer Growth, Diagnosis and Treatment
Current Gene Therapy Mesenchymal Stem Cells Enhanced Cardiac Nerve Sprouting via Nerve Growth Factor in a Rat Model of Myocardial Infarction
Current Pharmaceutical Design Mental Health Disorder Therapeutic Modalities Modified for the GMS
Current Psychiatry Reviews Effect of Nigella Sativa and Allium Sativum Coadminstered with Simvastatin in Dyslipidemia Patients: A Prospective, Randomized, Double-Blind Trial
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Hydroxyimine NO-Donors; FK409 and Derivatives
Current Topics in Medicinal Chemistry Mast Cell Chymase and Tryptase as Targets for Cardiovascular and Metabolic Diseases
Current Pharmaceutical Design Implication of Gut Microbiota in Human Health
CNS & Neurological Disorders - Drug Targets IL-1 Cytokines in Cardiovascular Disease: Diagnostic, Prognostic and Therapeutic Implications
Cardiovascular & Hematological Agents in Medicinal Chemistry Heterocyclic Chalcone Analogues as Potential Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry