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The Rational Design of T-Cell Epitopes With Enhanced Immunogenicity

  • John Fikes
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

For all cancer vaccine strategies, a major challenge facing efforts to induce a clinically effective T-cell response is the necessity to break tolerance to normal, “self” antigens. To control auto-reactivity, some T cells with high avidity for tumor-associated antigen (TAA) epitope—major histocompatibility (MHCs) complexes are deleted in the thymus and the remaining T cells are controlled by peripheral tolerance (1). However, several groups have demonstrated using in vitro systems that thymic-deletion of TAA-specific cytolytic T cell (CTL) is not complete (2–4). More importantly, it is clear that in some patients, natural exposure to tumor or immunization with wild-type antigens or epitopes can induce CTL of sufficient avidity and functionality to infiltrate tumors in vivo and/or recognize tumor cells in vitro. Therefore, although the fundamental vaccine strategy of targeting TAA to mount tumor-specific immune responses is supported, it remains a significant challenge to design cancer vaccine strategies that consistently overcome immunological tolerance in order to effectively activate and maintain therapeutic T-cell responses. Experimentation in the late 1980s and 1990s has resulted in a detailed understanding of the molecular mechanisms controlling T-cell activation and effector function. It is now appreciated that the interaction of a T-cell receptor with a peptide epitope presented by an antigen-presenting cell (APC) in the context of an MHC molecule generates the central event (referred to as “signal 1”) in the activation of naïve or memory T cells.

Keywords

Cancer Vaccine Single Amino Acid Substitution Altered Peptide Ligand Anchor Position Human Carcinoembryonic Antigen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  • John Fikes

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