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
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