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Viszeralchirurgie 2003; 38(4): 261-266
DOI: 10.1055/s-2003-41157
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Immunologie und Immuntherapie des kolorektalen Karzinoms

Immunology and Immuntherapy of Colorectal CarcinomesT.  Ahlert1 , P.  Sterk2 , T.  Schiedeck2 , H.-P.  Bruch2 , R.  Keller2
  • 1Biotechnologisches Praxislabor, Servicecentrale, Heidelberg
  • 2Klinik für Chirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
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Publication History

Publication Date:
12 August 2003 (online)

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Zusammenfassung

Das Immunsystem muss im Bereich des Darmes besonders subtil zwischen Freund (Nahrung) und Feind (Erregern/Tumorzellen) unterscheiden. Besonders im Bereich des Kolons und Rektums sind durch die notwendige Symbiose mit (E. coli-)Keimen und durch die hohe Belastung mit Schadstoffen hochentwickelte und robuste Immunfunktionen erforderlich. So verwundert es nicht, dass besonders spezifische Immunfunktionen bei spontanen Wechselwirkungen zwischen kolorektalen Tumorzellen und Immunsystem eine z. T. lebenswichtige Rolle spielen können. Auch immuntherapeutische Ansätze für das kolorektale Karzinom beziehen vor allem das spezifische Immunsystem ein. So finden sich antisuppressive Immuntherapien, die vor allem gegen Blockaden und Suppressionen des spezifischen Immunsystems gerichtet sind. Auch aktive unspezifische Immuntherapien wie der Einsatz von Levamisol wirken letztlich über die Begünstigung von spezifischen Immunfunktionen. Die moderne Immuntherapieforschung sucht mit aktiv spezifischen Immuntherapien, also mit Tumorimpfstoffen, den Durchbruch. Zahlreiche Tumorantigene und tumorassoziierte Antigene sind bereits als potenzielle Ziele solcher Therapien identifiziert worden. Sie werden in Vakzinierungsstudien, seltener in passiven spezifischen Immuntherapieansätzen mit (monoklonalen) Antikörpern und adoptiven Immunzelltransfers auf ihre therapeutische Nutzbarkeit geprüft. Bisher kommen die Ergebnisse noch nicht an Daten aus (z. T. randomisierten) Studien zur Tumorvakzinierung mit autologem (patienteigenem) Tumormaterial heran. Autologe Tumorimpfstoffe sind zwar in Herstellung und Qualitätssicherung aufwändiger als Impfstoffe, die aus synthetischem oder fremdem (allogenen) Material hergestellt werden. Aber der Vorteil der perfekten Übereinstimmung des Antigencocktails aus der Vakzine mit dem Antigenmuster auf den zu behandelnden Tumormetastasen überwiegt. Zukunftweisend scheinen neue Impfstoffgenerationen, die zur Verbesserung von Antigenität und Immunogenität allogener oder autologer Tumorantigene dendritische Zellen verwenden. Einige dieser Impfstoff sind zwar prinzipiell zur klinischen Routineanwendung verfügbar, das Evidenzniveau für die Wirksamkeit, Kosten und Patientenselektion setzen dem Einsatz jedoch noch Grenzen.

Abstract

The immune system around the bowel has to decide between friend (food) and enemy (pathegens/tumorcells) in a very subtle manner. Especially in the area of colon and rectum there is a strong need for highly sophisticated and reliable immune functions because of the symbiosis with potential pathogens (E. coli) and the presence of high concentrations of toxic chemicals. Consequently it is not surprising that the specific immune functions play a major and sometimes vital part within spontaneous interactions between colorectal tumor cells and the immune system. In the same way immunotherapeutic strategies for colorectal cancer center around the specific immune system. There are for example antisuppressive approaches antagonizing blocking and suppressive influences on the specific immune functions. Also active non-specific immunotherapy like levamisol application seems to act mainly via an indirec support of specific immune cells. Modern strategies in search for a break through are centred around active specific immunotherapies with tumor vaccines. Many tumor antigens and tumor associated antigens have been identified as possible targets for specific immune resonses. They are currently evaluated in vaccine studies, or though less often in passive specific therapies with (monoclonal) antibodies or adoptive immune cell transfer. However, up to now the results cannot compete with results from (randomized) clinical studies using vaccines from autologous (i.e. patients own) tumor material. Autologous tumor vaccines are on one hand more difficult to handle with respect to pharmaceutical production standards and quality control than vaccines made from synthetic or foreign (allogenous) tumor material. On the other hand the advantage of a perfect match between the antigen cocktail of the vaccine and the antigenic constellation in the metastases to be treated still dominates. Future developements introduce the use of dendritic cells as multiplier for antigenicity and immunogenicity of allogenous or autologous tumor materials. Some of these vaccine generations are basically available in clinical routine although the evidence level for effectivity, the cost and the patient selection put yet limits to their use.

Schlüsselwörter

Kolorektales Karzinom - Tumorvakzine - Tumorimpfung - Tumorvakzinierung Immunität - klinische Studie - spezifische Immuntherapie - Immunmechanismus - Tumorbiologie

Key words

Colorectal cancer - tumor vaccine - tumor vaccination - immunity - clinical study - specific immunotherapy - immune mechanism - tumor biology

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PD Dr. med. Peter Sterk

Klinik für Chirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Ratzeburger Allee 160

23538 Lübeck

Phone: + 0451/500-2001

Fax: + 0451/500-2069

Email: post@sterk-medic.de

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