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

2
Serological Determinants On Tumor Cells
Carsten Zwick, Klaus-Dieter Preuss, Claudia Wagner, Frank Neumann and
Michael Pfreundschuh
2.1
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)
The identification and molecular characterization of tumor antigens that elicit specific
immune responses in the tumor-bearing host is a major task in tumor immunology.
In the 1970s and 1980s monoclonal antibody technology was exploited for the
identification of molecules on tumor cells that could be used as diagnostic markers
or as target structures for immunotherapeutic approaches with monoclonal antibodies.
While some of these efforts have yielded newtherapeutic tools, such as the
anti-CD20 antibody rituximab that shows considerable activity and has been licensed
for the treatment of B cell lymphomas [1], approaches of active immunotherapy require
the identification of target structures which are immunogenic in the autologous
tumor-bearing host.
The analysis of humoral and cellular immune responses against such antigens in
cancer patients had indicated for a long time that cancer-specific antigens do indeed
exist which are recognized by the patient's immune system [2]. To define the molecular
nature of these antigens, cloning techniques were developed that used established
cytotoxic T lymphocyte (CTL) clones [3] or circulating antibodies [4] as probes
for screening tumor-derived expression libraries. While the molecular characterization
of the first human tumor antigens was accomplished with cloning techniques
that used established CTL clones [3], it is nowcommonly accepted that immune recognition
of tumors is a concerted action. Thus, high-titered circulating tumor-associated
antibodies of the IgG class may reflect a significant host±tumor interaction
and may identify such gene products to which at least cognate T cell help, but also
specific cytotoxic T cells, should exist. This rationale prompted us to design a novel
strategy using the antibody repertoire of cancer patients for the molecular definition
of antigens. Serologically defined antigens could then be subjected to procedures of
ªreverseº T cell immunology for the definition of epitopes which are presented by
MHC class I or II molecules, respectively, and are recognized by T lymphocytes.
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