Chapter category: Vaccines
DNA Vaccines as Cancer Treatment Modalities
DNA Vaccines
Edited by: Hildegund ErtlISBN: 0-306-47444-1
» Get more information about this book at landesbioscience.com «
Chapter authors:
Ronald C. Kennedy, Michael H. Shearer and Robert K. Bright
Therapeutic vaccination has recently regained its optimism as a potential immunologic based modality for the treatment of cancer patients. Cancer vaccine based clinical trials are being initiated at a rapid pace, yet work still must be performed to determine the best formulation of the vaccine, the optimal route for immunization, the most effective timing and course of therapy, and the best and most accurate methods for evaluating clinical efficacy. Early studies involving tumor vaccination employed whole tumor cells, fragments of tumor cells or protein containing lysates from tumor cells as the strategy. Limited results with these approaches have led investigators to develop the next generation of cancer vaccines using defined tumor‑associated antigens. With the discovery of new tumor antigens for common human malignancies, the formulation of the vaccine has been a focus. Most strategies attempt to invoke a predominant cell‑mediated immune response and virtually ignore the humoral aspect of the immune response. Yet, antibodies have been shown to play a role in tumor immunity and the currently most effective immuno‑therapeutic modalities use monoclonal antibodies to target the tumor antigen. One form of a universal vaccination strategy that can induce both components of the immune responses is represented by plasmid DNA encoding a foreign transgene product that represents the target antigen for the induction of a specific immune response. This vaccination strategy referred to as DNA or genetic immunization has been employed to induce a variety of immune responses against antigens from a variety of sources, including infectious agents and allergens. When the foreign transgene expresses a tumor antigen, the potential exists that the DNA immunization strategy will invoke an anti‑tumor immune response. This report will focus on the activities of DNA immunization that induce immune responses against tumor antigens and will discuss particular aspects of what immunologic correlates have been associated with protection against tumor progression in vivo. A discussion of specific systems will highlight the possible immunologic correlates of anti‑tumor immunity and will demonstrate that DNA‑based strategies represent a viable alternative for the development and testing of cancer vaccination strategies that target a particular tumor antigen.
Additional chapters from this book:
DNA Vaccines: Safety and Regulatory Issues
Dennis M. Klinman and Herbert A. Smith
Plans to initiate clinical trials involving DNA vaccines prompted the US Food and Drug Administration to examine the safety of this form of vaccination. Concerns were raised that DNA vaccin...
Cytokines and Immunomodulatory Ligands as Genetic Adjuvants
Hildegund C. J. Ertl
Genetic adjuvant is a term for vaccine ingredients composed of expression vectors encoding biologically active molecules such as cytokines, chemokines (detailed in Chapter 15), soluble form...
Immune Responses in Gene Transfer for Genetic Disorders
Denise E. Sabatino and Katherine A. High
Gene transfer is a novel area of therapeutics in which a nucleic acid sequence is the active agent. Transferred in via a gene delivery vehicle, or vector, the donated gene sequence, referre...
DNA Vaccines for Allergic Diseases
Kaw Yan Chua, Betina Wolfowicz and Patrick G. Holt
DNA vaccines have prevented anaphylaxis in several models of murine allergy. The mechanisms of prevention are still unclear. In this chapter we describe different immunization protocols with a...
DNA Vaccines as Cancer Treatment Modalities
Ronald C. Kennedy, Michael H. Shearer and Robert K. Bright
Therapeutic vaccination has recently regained its optimism as a potential immunologic based modality for the treatment of cancer patients. Cancer vaccine based clinical trials are being initia...
Genetic Immunization Against HIV
Britta Wahren, Karl Ljungberg, Anne Kjerrstrˆm Zuber and Bartek Zuber
The HIV virus and its subtypes are spread worldwide. AIDS has become the worldís most threatening infectious disease. The picture of the epidemic has changed: several subtypes and recombina...
DNA Vaccines Against Herpesviruses
Christopher Pack and Barry T. Rouse
Herpesviruses are significant pathogens of mankind, and vaccines of proven efficacy remain unavailable. This review briefly examines the current state of vaccinology against herpesviruses and ...
DNA Vaccines Against RNA Viruses
Jeffrey B. Ulmer
DNA vaccines have been used successfully in many animal models of infectious and non‑infectious diseases. The former has included viruses, bacteria, parasites, and other pathogens. Howev...
Minigene-Based Vaccines for Eliciting CD8+ T Cell Responses
Jonathan W. Yewdell
There is increasing interest in developing vaccines that specifically elicit CD8+ T cell responses. In part this has been driven simply by advances in understanding that make suc...
Induction of B Cells by DNA Vaccines
K. Kilpatrick, M. Sarzotti and G. Kelsoe
Antigen first activates T and B lymphocytes in the T cell areas of secondary lymphoid tissues where cognate‑ and costimulus‑dependent proliferation expands the population of reacti...
Activation of the Innate Immune System by DNA Vaccines
Julie Fitzgerald and Hildegund C. J. Ertl
DNAvaccines were discovered serendipitously by gene therapists attempting to replace missing or faulty genes with bacterial expression vectors. The transgene product was found to elicit an ...
Dendritic Cells: Important Adjuvants During DNA Vaccinati
Ralph M. Steinman, Constantin Bona and Kayo Inaba
Vaccine design focuses on the identification of safe forms of antigen that elicit protective immunity. Adjuvants are also critical for efficacy, especially for inducing strong T cell‑...
Overview of Vaccinology in Historic and Future Perspective: The Whence and Whither of a Dynamic Science with Complex Dimensions
Maurice R. Maurice R. Hilleman
Understanding of the present and future can be aided immensely by acquaintance with a breadth of knowledge of the past. The history of the world records its dread experiences with diseases,...
DNA Vaccines Against Bacterial Pathogens
M.A. Chambers, H.M.Vordermeier, R.G. Hewinson and D.B. Lowrie
Bacterial pathogens against which DNA vaccines are being developed encompass both intracellular and extra-cellular pathogens as well as vaccines against bacterial toxins. DNA vaccination has a...
The Introduction of New DNA Vaccines into Developing Countries
Richard T. Mahoney, Yu-Mei Wen, Henry Wilde and
The development and introduction of new vaccines is a costly and time-consuming process. Unfortunately, those most in needindividuals in developing countriesare the las...
The Use of DNA Vaccines for Neonatal/Early Life Childhood Immunization
Jiri Kovarik, Xavier Martinez, ClaireAnne Siegrist
DNA vaccines could represent a major advancement in the development of novel antigen-delivery systems to be used in early life, although the demonstration of their effi...
Immune Responses to DNA Vaccines: Induction of CD8+
Jens A. Leifert and J. Lindsay Whitton
The importance of CD8+ T cells in the control and eradication of viruses has been demonstrated in mice and men. In the mouse, they are critical in combating ...
Chemokines: Role as Immunomodulators and Potential as Adjuvants for DNA Vaccines
Philip M. Murphy
Adaptive immune responses require proper positioning of antigenpresenting cells (APCs) and antigenspecific lymphocytes in specific microdomains of secondary lymphoid tissue. This process is gu...
DNA Delivery With Attenuated Intracellular Bacteria
Joachim Fensterle and Stefan H.E. Kaufmann
For centuries, intracellular bacteria have been a major cause of death globally. Notably, Mycobacterium tuberculosis killed more than 2 million individuals in 1999 worl...
