Immuntherapie bei gastrointestinalen Tumoren

Krebserkrankungen des Magen-Darm-Trakts bilden die größte Gruppe an soliden Tumorerkrankungen in Deutschland. Die Prognose bei Diagnosestellung ist häufig kritisch. Medikamentöse Therapien senken das Rückfallrisiko nach Resektionen und vermögen das Fortschreiten bei metastasierter Erkrankung aufzuhalten. Immuntherapien leisten einen zunehmenden Beitrag in der Behandlung gastrointestinaler Tumoren.

Abstract

Cancers of gastrointestinal tract make up the largest group of solid tumour diseases in Germany. The prognosis at diagnosis is often critical. Drug therapies reduce the risk of relapse after resection and can halt the progression of metastatic disease. Immunotherapies contribute increasingly to the treatment of gastrointestinal tumours. Monoclonal antibodies (mAB) against surface receptors from the epidermal growth factor receptor family (EGFR, Her2) are well established. The effect is partly based on the interruption of the oncogenic downstream signalling cascades and partly on immune effector mechanisms such as antibody-dependent cellular cytotoxicity. In clinical practice mAB directed against programmed cell death protein 1 (PD-1), its ligand (PD-L1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) – so-called immune checkpoint inhibitors – play an increasing role and change the natural history of some subgroups of gastrointestinal cancers, especially those with deficient DNA mismatch repair which leads to genomic microsatellite instability.

Kernaussagen

• Immuntherapie leistet einen zunehmenden Beitrag in der Behandlung gastrointestinaler Tumoren.

• Monoklonale Antikörper gegen Oberflächenrezeptoren aus der Familie der epidermalen Wachstumsfaktor-Rezeptoren (EGFR bei kolorektalem Karzinom, HER2 bei Magenkarzinom) sind in der Therapie gastrointestinaler Tumoren bereits gut etabliert.

• Monoklonale Antikörper gegen Immuncheckpoints (PD-1, PD-L1 und CTLA-4) stellen für die Therapie gastrointestinaler Tumoren einen Meilenstein dar.

• Checkpoint-Inhibitoren sind hoch wirksam bei Karzinomen mit defizienter DNA-Mismatch-Reparatur und daraus folgender Mikrosatelliten-Instabilität.

• In der Europäischen Union zugelassene Immuncheckpoint-Inhibitoren finden jenseits der Mikrosatelliten-Instabilität bei Ösophaguskarzinom, Magenkarzinom und bei primären Lebertumoren (hepatozelluläre und biliäre Karzinome) Anwendung.

• Antikörper-Wirkstoff-Konjugate (ADC) sind mAK gegen Oberflächenrezeptoren, die über eine chemische Brücke (Linker) mit einem zytotoxischen Wirkstoff verbunden sind. Der HER2-gerichtete ADC Trastuzumab-Deruxtecan findet beim HER2-positiven Magenkarzinom Anwendung.

Schlüsselwörter

Immuntherapie - gastrointestinaler Krebs - Immuncheckpoint-Inhibitoren - monoklonale Antikörper - Antikörper-Wirkstoff-Konjugate

Keywords

immunotherapy - gastrointestinal cancer - immune checkpoint inhibitors - monoclonal antibodies - antibody drug conjugates

Publication History

Article published online:
02 April 2024

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