Prevention of Brain Metastasis Formation by Local Expression of Interleukin-4 or Hemagglutinin Antigen

Abstract

Introduction: Expression of hemagglutinin antigen of influenzavirus (HA) by the murine colon carcinoma cell line (CT-26) produces systemic immunization against tumor challenges in the cecum, liver and lungs but not in the brain of BALB/c-mice. Immunization with IL-4 expressing CT-26 cells inhibits lung metastases formation. The purpose of our study was to examine the effects of HA or IL-4 expression on brain metastases formation.
Methods: Using selective internal carotid artery injections, brain metastases formation of HA or IL-4 expressing CT-26 cells with and without subcutaneous pre-immunization was evaluated in Balb/c mice.
Results: Systemic pre-immunization with HA or IL-4 expressing tumor cells cannot protect against brain metastases, while the local, intracerebral expression of HA or IL-4 inhibits the growth of hematogenous brain metastases.
Conclusion: Pre-immunization with HA or IL-4 expressing tumor cells did produce systemic immunity against liver and lung metastases but not against brain metastases. Local, intracerebral expression of HA or IL-4 prevents from cerebral metastases formation in an animal model.

Zusammenfassung

Einführung: Die Expression des Hämagglutinin-Antigens des Influenzavirus (HA) nach Gentransfer in die murine Kolonkarzinomzelllinie CT-26 führt zu einer systemischen Immunisierung gegen diesen Tumor in Zökum, Leber und Lunge, nicht aber im Gehirn von Balb/c Mäusen. Die Immunisierung mit IL-4 exprimierenden CT-26 Zellen verhindert das Auftreten von Lungenmetastasen. Das Ziel dieser Arbeit war die Untersuchung der zerebralen Metastasenbildung von HA- oder IL-4-exprimierenden CT-26 Zellen.
Methoden: Nach selektiver Injektion von Tumorzellen in die Arteria carotis interna wurde die Metastasenbildung in Abhängigkeit der Expression von IL-4 oder HA studiert.
Ergebnisse: Während die systemische Präimmunisierung mit HA oder IL-4 exprimierenden Tumorzellen nicht zu einer reduzierten zerebralen Metastasierung von CT-26 Zellen führt, verhindert die lokale Expression von IL-4 oder HA das Wachstum zerebraler Metastasen.
Zusammenfassung: Die Vorimmunisierung mit HA- oder IL-4- exprimierenden Tumorzellen führt zu einer systemischen Immunität gegen Leber- und Lungenmetastasen nicht jedoch gegen Hirnmetastasen. Die lokale intrazerebrale Expression von HA oder IL-4 verhindert jedoch das Tumorwachstum in diesem Tiermodell.

Key words

Brain metastasis formation - immunotherapy - interleukin-4 - hemagglutinin

Schlüsselwörter

Zerebrale Metastasen - Immuntherapy - Interleukin-4 - Hämagglutinin-Antigen

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