Tumorvakzinierung –Strategien und Timing

Tumor vaccination—strategies and time points

Zusammenfassung

Hintergrund

Immuntherapien haben in den vergangenen Jahren einen zunehmenden Stellenwert in der Behandlung maligner Erkrankungen gewonnen. Hierzu gehören auch Tumorvakzine, die therapeutisch eingesetzt werden, um das Immunsystem spezifisch gegen Tumorzellen zu richten.

Fragestellung

Es werden verschiedene Strategien der Tumorvakzinierungen, ihr aktueller Entwicklungstand, der optimale Einsatzzeitpunkt und Kombinationsmöglichkeiten in der Therapie von malignen Erkrankungen diskutiert.

Methoden

Wissenschaftliche Publikationen zu unterschiedlichen Tumorvakzinierungsstrategien unter Einbeziehung aktueller Studien werden zusammengefasst.

Schlussfolgerung

Für eine effektive Tumorvakzinierung ist die Auswahl geeigneter Tumorantigene, die über Moleküle der humanen Leukozytenantigene (HLA) auf der Zelloberfläche präsentiert werden, essenziell. Geeignete Antigene müssen sowohl exklusiv auf den Tumorzellen präsentiert werden als auch eine spezifische Antitumorimmunantwort induzieren, d. h. zytotoxische und T‑Helferzellen aktivieren. Hierfür kommen einerseits Neoepitope, die aus tumorspezifischen Mutationen stammen, und andererseits tumorassoziierte Antigene (TAA), die durch veränderte Genexpression oder Prozessierung ausschließlich im Tumorgewebe präsentiert sind, infrage. Für die Applikation der Antigene stehen verschiedenste Strategien, wie u. a. Peptidvakzine, DNS- oder RNS-basierte Vakzine sowie auf dendritischen Zellen oder kompletten Tumorzellen basierende Ansätze, kombiniert mit geeigneten Adjuvanzien zur Verfügung. Derzeit wird die Wirksamkeit zahlreicher Vakzinierungskonzepte und Kombinationsprotokolle in klinischen Studien im Hinblick auf Tumorreduktion und Rezidivprävention evaluiert.

Abstract

Background

Immunotherapies have gained increasing importance in the treatment of cancer in recent years. This also includes tumor vaccines, which are used therapeutically to direct the immune system specifically against tumor cells.

Objectives

Different strategies of tumor vaccination, their current state of development, the optimal timing and possible combinations of cancer vaccines in the treatment of cancer are discussed.

Methods

Scientific publications on various tumor vaccination strategies based on ongoing studies that are listed on clinicaltrials.gov are summarized.

Conclusions

For effective tumor vaccination, the selection of suitable tumor antigens present on the cell surface via human leukocyte antigen (HLA) molecules is essential. Suitable antigens should be present exclusively on tumor cells and able to induce a specific anti-tumor immune response, i.e. activate cytotoxic and T helper cells. For this purpose, neoepitopes derived from tumor-specific mutations or tumor-associated antigens (TAAs), which are present exclusively in tumor tissue due to altered gene expression or processing, can be used. For the application of the antigens, various strategies combined with suitable adjuvants are available, including peptide vaccines, DNA- or RNA-based vaccines, approaches with dendritic cells or whole tumor cell vaccines. Currently, numerous vaccination approaches as well as combination protocols are being evaluated in clinical trials with the aim to establish specific and low side effect immunotherapies to combat malignancies and enable long-term protection from disease recurrence via the induction of long-lasting antitumor immune responses.

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Correspondence to Juliane S. Walz.

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Interessenkonflikt

Y. Maringer und J.S. Walz geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Maringer, Y., Walz, J.S. Tumorvakzinierung –Strategien und Timing. Gastroenterologe 16, 241–248 (2021). https://doi.org/10.1007/s11377-021-00532-4

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Schlüsselwörter

  • Tumorvakzine
  • Tumorantigen
  • Immuntherapie
  • T‑Lymphozyten
  • HLA-Antigene

Keywords

  • Cancer vaccines
  • Tumor antigen
  • Immunotherapy
  • T‑Lymphocytes
  • HLA antigens