Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

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Search for Universal Tumor-Associated T Cell Epitopes
Robert H. Vonderheide and Joachim L. Schultze
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Introduction
Cancer Immune Therapie: Current and Future Strategies
Edited by G. Stuhler and P. Walden
Copyright # 2002 Wiley-VCH Verlag GmbH & Co. KGaA
ISBNs: 3-527-30441-X (Hardback); 3-527-60079-5
(Electronic)
Definitive proof over the last 10 years that human cancers express antigens which
can be specifically targeted by cellular immunity has accelerated efforts to design
strategies for T lymphocyte-based anti-cancer immunotherapy. To date, the promise
of such strategies has outweighed clinical results, but knowledge gained from early
trials coupled with the impressive development of novel adjuvants and delivery modalities
justifies continued enthusiasm. Clinical immunologists and oncologists involved
in T cell immunotherapy make note of the long road required for monoclonal
serotherapy to emerge as a powerful new therapeutic tool after years of frustrating
results. For the development of both humoral and cellular immunotherapy, the identification
of tumor-associated targets is the keystone of the approach. Since 1990, a
growing array of tumor-associated T cell epitopes have been identified for particular
malignant histologies, driving clinical trials particularly in melanoma that test these
targets either alone or in combination. Despite the fact that most tumor antigens described
thus far are restricted to a few tumor types ± and to a subset of patients who
have these tumors ± the demonstration that tumor-associated antigens do exist in
human cancer also provides part of the rationale behind tumor cell-based therapies
in which the targeted antigens are not expressly defined. In this chapter, we explore
the hypothesis that recent developments in T cell biology and tumor immunology
make it possible to extend the search for appropriate targets to universal, or near-universal,
tumor-associated antigens. Furthermore, the results of the Human Genome
Project, improved bioinformatics tools and optimized immunological analytical tools
enable any given protein to be screened for immunogenic eptitopes that might be incorporated
into new therapies. The bench-to-bedside transition from cancer genomics
to cancer immunology to clinical oncology is now underway.
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