Adaptive Immuntherapie des fortgeschrittenen Prostatakarzinoms - Cancer Testis Antigene (CTA) als mögliche Zielantigene

Zusammenfassung

Das Prostatakarzinom (PCa) wie auch andere Tumoren exprimieren Antigene, die als Angriffspunkte für eine spezifische Immuntherapie dienen können. Spezielle antigenpräsentierende Zellen (z. B. dendritische Zellen) bieten dabei dem Immunsystem die Antigene an, so dass eine entsprechende Antwort ausgelöst wird. Sehr effektiv gehen dabei zytotoxische T-Zellen (sog. Killerzellen) gegen die Antigene und somit gegen das entsprechende Gewebe respektive den Tumor vor. Cancer Testis Antigene (CTA) werden in verschiedenen menschlichen Karzinomen exprimiert, außer im Hoden aber nicht in normalem Gewebe. Sie eignen sich damit ideal für eine spezifische Tumor-Immuntherapie. Wir untersuchten, ob einige dieser CTA (LAGE-1, PRAME, MAGE-C2, NY-ESO-1, SSX-2 und PAGE4) auch im Prostatakarzinom vorkommen. Dabei zeigte sich eine sehr heterogene Expression der CTA in verschiedenen PCa-Zelllinien oder PCa-Proben aus unserem Patientengut. Nur PAGE4 wies neben einer Expression in primären PCa und LnCaP-Zellen auch eine Expression in hormonabhängigen und -refraktären PCa-Proben auf, so dass es als mögliches Zielantigen zur Immuntherapie des PCa weiter evaluiert wird.

Abstract

Prostate cancer (PCa) like other tumors expresses antigens that may serve as target for specific immunotherapy. Special antigen-presenting cells (e. g., dendritic cells) are capable of generating tumor-specific immunity. Cytotoxic T-cells (killer cells) are very effective against antigens and, consequently, against the respective tissue or tumor. Cancer testis antigens (CTA) are expressed in various human cancers but, aside from the testicles, not in normal tissue. Therefore, they are suitable for a specific tumor immunotherapy. We looked at different CTA (LAGE-1, PRAME, MAGE-C2, NY-ESO-1, SSX-2 and PAGE4) and their occurrence in prostatic cancer. Expression of CTA in various PCa cell lines and PCa material from patients was very heterogeneous. Only PAGE4 was expressed in primary PCa and in LnCaP cells as well as in hormone-dependent and hormone-refractory PCa probes. We conclude that PAGE4 should be further evaluated as a potential target for immunotherapy of PCa.

Prostatakarzinom - Immuntherapie - Cancer Testis Antigen - dendritische Zellen

Prostatic cancer - immunotherapy - cancer testis antigens - dendritic cells

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