Abstract
For the immune system to mount an effective antitumor T-cell response, an adequate number of T-cells specific for the antigens expressed by the malignancy must be activated [1]. Since most antigens expressed by tumors are "self"- antigens, tumor antigens often lack endogenous immunogenicity and thus do not sufficiently activate T-cells to levels that can mediate tumor eradication. In addition, virtually all solid tumor cells lack the costimulatory molecules necessary to activate tumor-specific T-cells. Approaches that stimulate immune responses to these tumor antigens have the potential to alter this poor responsiveness. This theory has promoted the use of active immunotherapy to generate immune responses against tumor-associated antigens (TAAs) for the treatment of cancer. As one such vaccine strategy, we have utilized poxviruses as delivery vehicles for TAAs in combination with T-cell costimulatory molecules. Initial studies have demonstrated that the insertion of costimulatory molecule trangenes into viral vectors, along with a TAA transgene, greatly enhances the immune response to the antigen. Using this approach, a TRIad of COstimulatory Molecules (TRICOM; B7-1, ICAM-1 and LFA-3) has been shown to enhance T-cell responses to TAAs to levels far greater than any one or two of the costimulatory molecules in combination. In this article, preclinical findings and recent clinical applications of TRICOMbased vaccines as a cancer immunotherapy are reviewed.
Keywords: TRICOM, costimulation, vaccination, TAA, cancer immunotherapy
Current Pharmaceutical Design
Title: TRICOM Vector Based Cancer Vaccines
Volume: 12 Issue: 3
Author(s): Charlie T. Garnett, John W. Greiner, Kwong-Yok Tsang, Chie Kudo-Saito, Douglas W. Grosenbach, Mala Chakraborty, James L. Gulley, Philip M. Arlen, Jeffrey Schlom and James W. Hodge
Affiliation:
Keywords: TRICOM, costimulation, vaccination, TAA, cancer immunotherapy
Abstract: For the immune system to mount an effective antitumor T-cell response, an adequate number of T-cells specific for the antigens expressed by the malignancy must be activated [1]. Since most antigens expressed by tumors are "self"- antigens, tumor antigens often lack endogenous immunogenicity and thus do not sufficiently activate T-cells to levels that can mediate tumor eradication. In addition, virtually all solid tumor cells lack the costimulatory molecules necessary to activate tumor-specific T-cells. Approaches that stimulate immune responses to these tumor antigens have the potential to alter this poor responsiveness. This theory has promoted the use of active immunotherapy to generate immune responses against tumor-associated antigens (TAAs) for the treatment of cancer. As one such vaccine strategy, we have utilized poxviruses as delivery vehicles for TAAs in combination with T-cell costimulatory molecules. Initial studies have demonstrated that the insertion of costimulatory molecule trangenes into viral vectors, along with a TAA transgene, greatly enhances the immune response to the antigen. Using this approach, a TRIad of COstimulatory Molecules (TRICOM; B7-1, ICAM-1 and LFA-3) has been shown to enhance T-cell responses to TAAs to levels far greater than any one or two of the costimulatory molecules in combination. In this article, preclinical findings and recent clinical applications of TRICOMbased vaccines as a cancer immunotherapy are reviewed.
Export Options
About this article
Cite this article as:
Garnett T. Charlie, Greiner W. John, Tsang Kwong-Yok, Kudo-Saito Chie, Grosenbach W. Douglas, Chakraborty Mala, Gulley L. James, Arlen M. Philip, Schlom Jeffrey and Hodge W. James, TRICOM Vector Based Cancer Vaccines, Current Pharmaceutical Design 2006; 12 (3) . https://dx.doi.org/10.2174/138161206775201929
DOI https://dx.doi.org/10.2174/138161206775201929 |
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
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...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
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...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
-
Prognostic Value and Clinicopathological Differences of Bmi1 in Gastric Cancer: A Meta-analysis
Anti-Cancer Agents in Medicinal Chemistry Cancer Stem Cell Markers in Nasopharyngeal Carcinoma and Its Relevance for Therapy
Current Traditional Medicine Reduced Nicotinamide Adenine Dinucleotide (NADH) Fluorescence for the Detection of Cell Death
Anti-Cancer Agents in Medicinal Chemistry Open Architecture PCR-Based Methods for Differential Gene Expression Analysis
Current Pharmaceutical Analysis A Multimodal Ultrasound Observation Study on the Effect of Vitamin D on Uterine Fibroids in Non-menopausal Women
Current Medical Imaging Polyphenols in Food: Cancer Prevention and Apoptosis Induction
Current Medicinal Chemistry Fighting Fire with Fire: A Patent for the Combined Application of Oncolytic Herpes Viruses and Antiangiogenic Agents in the Battle Against Human Cancers
Recent Patents on Anti-Cancer Drug Discovery Targeting Cancer Cells by an Oxidant-Based Therapy
Current Molecular Pharmacology Regulation of MicroRNAs by Phytochemicals: A Promising Strategy for Cancer Chemoprevention
Current Cancer Drug Targets Circulating Tumor Stem Cells as Biomarkers for Cancer Progression
Recent Patents on Biomarkers Strategies for Targeting CIB1: A Challenging Drug Target
Current Pharmaceutical Design Nanoinformatics and Personalized Medicine: An Advanced Cumulative Approach for Cancer Management
Current Medicinal Chemistry Current Developments of Coumarin Compounds in Medicinal Chemistry
Current Pharmaceutical Design Antibody Targeting of TGF-β in Cancer Patients
Current Pharmaceutical Biotechnology NK Cell Receptor and MHC Gene Polymorphisms, Potential Relevance in Malignancies
Current Cancer Therapy Reviews Laparoscopic Reconstructive Surgery in Pediatric Urology: An Overview of Current Options
Current Pediatric Reviews Detection of Fungal Infections Using Radiolabeled Antifungal Agents
Current Drug Targets Anti-Epidermal Growth Factor Receptor Antibodies in the Treatment of Metastatic Colorectal Cancer
Recent Patents on Anti-Cancer Drug Discovery Nanotechnological Systems and Lung: A Perfect Combination for Lung Pharmaceutical Applications
Current Medicinal Chemistry Plant Coumestans: Recent Advances and Future Perspectives in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry