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
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
-
Extracellular ATP and Neurodegeneration
Current Drug Targets - CNS & Neurological Disorders OX40 and OX40L Interaction in Cancer
Current Medicinal Chemistry Molecular Recognition at Purine and Pyrimidine Nucleotide (P2) Receptors
Current Topics in Medicinal Chemistry Functionalized Nanocarriers for Enhanced Bioactive Delivery to Squamous Cell Carcinomas: Targeting Approaches and Related Biopharmaceutical Aspects
Current Pharmaceutical Design GPR55, a Lysophosphatidylinositol Receptor with Cannabinoid Sensitivity?
Current Topics in Medicinal Chemistry Medical Image Processing Technology for Diagnosing and Treating Cancers
Recent Patents on Biomedical Engineering (Discontinued) Bortezomib Enhances the Antitumor Effects of Interferon-β Gene Transfer on Melanoma Cells
Anti-Cancer Agents in Medicinal Chemistry Nanomedicine as a Strategy for Natural Compound Delivery to Prevent and Treat Cancers
Current Pharmaceutical Design Mesenchymal Stem Cells for Treatment of CNS Injury
Current Neuropharmacology Drug Targeting Strategies for Photodynamic Therapy
Anti-Cancer Agents in Medicinal Chemistry Is the Clinical Use of Cannabis by Oncology Patients Advisable?
Current Medicinal Chemistry 4-Anilinoquinazoline Derivatives with Epidermal Growth Factor Receptor Inhibitor Activity
Anti-Cancer Agents in Medicinal Chemistry Prospects for Plant-Derived Chemopreventive Agents Exhibiting Multiple Mechanisms of Action
Current Medicinal Chemistry - Anti-Cancer Agents Identification of AHSA1 as a Potential Therapeutic Target for Breast Cancer: Bioinformatics Analysis and <i>in vitro</i> Studies
Current Cancer Drug Targets Resistance to Anti-VEGF Agents
Current Pharmaceutical Design Mitophagy in Carcinogenesis and Tumour Progression- A New Paradigm with Emerging Importance
Anti-Cancer Agents in Medicinal Chemistry The Interactions Between Diabetes Mellitus and Myelodysplastic Syndromes: Current State of Evidence and Future Directions
Current Diabetes Reviews Head and Neck Cancer Treatments through Chemotherapy to Magnetic Systems: Perspectives and Challenges
Current Radiopharmaceuticals Fluorescence Detection of MMP-9. II. Ratiometric FRET-Based Sensing With Dually Labeled Specific Peptide
Current Pharmaceutical Biotechnology Bioinorganic Chemistry: The Study of the Fate of Platinum-Based Antitumour Drugs
Current Chemical Biology