Der Onkologe

, Volume 11, Issue 5, pp 489–493 | Cite as

Identifizierung von Zielantigenen für Antikörper und T-Zellen

Leitthema
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Zusammenfassung

Grundsätzlich eignen sich alle Proteine mit spezifischer oder überwiegender Expression in Tumorgewebe als Zielstrukturen aktiver bzw. passiver immuntherapeutischer Strategien. Die klinischen Erfolge der letzten Jahre ermutigen die Forschung zur Identifizierung neuer Zielstrukturen. Geeignete Kandidaten sind neben tumoreigenen Proteinen auch solche, die vom Tumorstroma mit hoher Spezifität und Selektivität überexprimiert werden. Dazu gehören z. B. Wachstumsfaktoren, extrazelluläre Matrixproteine und Zelloberflächenproteine neu gebildeter Tumorgefäße. Die Suche nach Kandidatenantigenen erfolgte zunächst mit vorab generierten antitumoralen Antikörpern bzw. T-Zellen, mittlerweile aber überwiegend mit molekularbiologischen und proteinchemischen Hochdurchsatz-Screeningverfahren sowie Datenbankanalysen. Die präklinische Validierung der Kandidatenantigene umfasst neben Untersuchungen zur Verteilung, Homogenität und Stärke ihrer Expression auch die Analyse ihrer funktionellen Bedeutung und – insbesondere für Vakzinierungsstrategien – ihrer tatsächlichen Immunogenität.

Schlüsselwörter

Spezifische Immuntherapeutika T-Zellen Antikörper Tumorantigene Tumorstroma Antigenidentifizierung Antigenvalidierung 

Identification of target antigens for antibodies and T cells

Abstract

In principal, all proteins specifically or preferentially expressed in tumor tissues can be regarded as target candidates for active or passive immunotherapy strategies. Clinical success achieved in the past years promotes the identification of new target structures. Aside from proteins expressed by the tumor itself also proteins overexpressed by stromal cells are regarded as suitable candidates. Among the latter are e.g. growth factors, extracellular matrix proteins and cell surface proteins of the tumor neovasculature. The search for candidate target antigens originally depended on the availability of anti-tumor antibodies or T cells, respectively. But in the meantime genomic and proteomic high-throughput screening techniques and data mining procedures clearly dominate. The preclinical validation of candidate antigens includes expression profiling as well as analyses on their functional relevance and – especially for vaccine candidates – their immunogenicity.

Keywords

Specific immunotherapeutics T cells Antibodies Tumor antigens Tumor stroma antigen identification Antigen validation 
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Notes

Interessenkonflikt:

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Copyright information

© Springer Medizin Verlag 2005

Authors and Affiliations

  1. 1.III. Medizinische Klinik der Universität Mainz
  2. 2.III. Medizinische Klinik der Universität MainzMainz

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