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Neue Entwicklungen in der Immunonkologie

New developments in immuno-oncology

Zusammenfassung

Die Entwicklung der Checkpointblockade und der chimären Antigenrezeptoren (CAR) markieren nicht das Ende, sondern den Anfang eines nie dagewesenen Innovationsschubs um die Immuntherapie in der Hämatologie und der Onkologie. Viele neue Entwicklungen im Bereich der unspezifischen Immunonkologie haben das Ziel, als Kombinationspartner mit der Checkpointblockade bei Patienten mit potenziell auf diese Therapie ansprechenden Tumoren die Ansprechrate und/oder die Ansprechdauer zu erhöhen. Neben der Entwicklung von Modulatoren weiterer Checkpointmoleküle ist in diesem Bereich v. a. die Entwicklung weiterer Immuntherapeutika zu beobachten, die nicht den Tumor selbst ansprechen, sondern primär das immunologisch Tumormilieu alterieren sollen. In diesem Zusammenhang gewinnt auch die intratumorale Therapie mit proinflammatorischen Substanzen zunehmend an Bedeutung. Neue Entwicklungen im Bereich der gerichteten Zelltherapie betreffen u. a. Zielantigene, Kostimulation und Auswahl und zusätzliche Modifikation der Effektorzellen, v. a. im Hinblick auf die Entwicklung allogener Effektorsysteme. In Zukunft ist eine zunehmende Diversifizierung von Tumorerkrankungen durch immunologische Diagnostik und prädiktive Marker zu erwarten. Die kommende Herausforderung wird sein, vor diesem Hintergrund rationale Strategien für sequenzielle und kombinierte Immuntherapien zu etablieren.

Abstract

The development of checkpoint inhibition and chimeric antigen receptors (CAR) marks not the end but the beginning of an unprecedented innovation drive in the immunotherapy of hematological and oncological diseases. Many experimental drugs in the field of unspecific immunotherapy are developed as combination partners for checkpoint inhibition in patients with tumors potentially responsive to such treatments with the aim to increase response rates and/or duration of responses. In addition to the development of modulators of additional checkpoint molecules, we observe the development of multiple substances targeting the immunological tumor environment rather than the tumor cell itself. In this context, intratumoral application of pro-inflammatory drugs is gaining relevance. New developments in the field of targeted cell therapy include new target antigens, costimulation and the selection and additional modification of effector cells with a main emphasis on development of allogeneic effector systems. The future will bring further diversification of malignant diseases due to immunological diagnostics and predictive markers. The challenge to come will be the establishment of rational strategies for sequential and combination treatment.

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Correspondence to S. Ochsenreither.

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S. Ochsenreither gibt 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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Ochsenreither, S. Neue Entwicklungen in der Immunonkologie. Onkologe (2021). https://doi.org/10.1007/s00761-021-01013-7

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Schlüsselwörter

  • Checkpoint-Modulation
  • Tumormilieu
  • Intratumorale Therapie
  • Chimärer Antigenrezeptor
  • Bispezifischer T‑Zell-Aktivator

Keywords

  • Checkpoint modulation
  • Tumor environment
  • Intratumoral therapy
  • Chimeric antigen receptor
  • Bispecific T‑cell engager