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Antikörper-Wirkstoff-Konjugate als neues Wirkprinzip in der Uroonkologie

Antibody–drug conjugates as new therapeutic agents in uro-oncology

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An Erratum to this article was published on 04 August 2023

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Zusammenfassung

Antikörper-Wirkstoff-Konjugate („antibody-drug conjugates“, rADC) stellen eine neue Substanzklasse dar, die seit kurzem auch in der Uroonkologie Anwendung finden. Sie bestehen aus einem Antikörper, der gegen ein spezifisches Tumorantigen gerichtet ist. Dieser ist über einen „linker“ an eine zytotoxische Substanz („payload“) gebunden, welche nach Internalisierung in die Tumorzelle und Freisetzung wirkt. Aktuell für urologische Tumoren in der EU zugelassen ist lediglich Enfortumab-Vedotin (EV), welches gegen Nectin‑4 gerichtet ist und den Mikrotubuli-hemmenden Wirkstoff Monomethyl-Auristatin E (MMAE) trägt. EV ist beim lokal fortgeschrittenen oder metastasierten Urothelkarzinom in der dritten Therapielinie nach Platin-haltiger Chemotherapie und nach Therapie mit einem PD-(L)1(„programmed cell death ligand 1“)-Immun-Checkpoint-Inhibitor (ICI) indiziert. EV als Monotherapie sowie in Kombination mit PD-(L)1-ICI sowie weitere ADC werden derzeit in mehreren klinischen Studien untersucht. Dies könnte u. a. die Therapiesequenz beim Urothelkarzinom nachhaltig verändern. Dieser Artikel stellt die neue Substanzklasse der ADC, deren Wirkmechanismus und aktuell laufende klinischen Studien mit Fokus auf Enfortumab-Vedotin vor, dabei werden auch praxisrelevante Nebenwirkungen von EV sowie der Umgang mit diesen aufgezeigt.

Abstract

Antibody–drug conjugates represent a new class of therapeutic agents that are already being used in the field of uro-oncology. They consist of an antibody directed against a specific tumour antigen linked to a cytotoxic substance (“payload”) which acts after internalisation into the tumour cell and its release. Currently, approval in the European Union is restricted to enfortumab vedotin which is directed against nectin‑4 and carries the microtubule-inhibiting active ingredient monomethyl auristatin E (MMAE). Enfortumab vedotin is approved for locally advanced or metastatic urothelial carcinoma in the third line of therapy after platinum-based chemotherapy and after therapy with a programmed cell death (ligand) 1 (PD-[L]1) immune checkpoint inhibitor. However, an expansion of the indication of enfortumab vedotin as monotherapy and in combination with PD-(L)1 immune checkpoint inhibitors, as well as approval of other antibody–drug conjugates is expected in the future. This could sustainably change the therapy sequence in urothelial carcinoma. Currently, several clinical trials are recruiting in different therapeutic settings. This article presents the new substance class of antibody–drug conjugates, their mechanism of action, their representatives and clinical studies, and points out practice-relevant side effects and how to deal with them.

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Authors and Affiliations

  1. Urologische Klinik und Poliklinik, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland

    Marc-Oliver Grimm, Susan Foller, Mirjam Leeder & Katharina Leucht

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  1. Marc-Oliver Grimm
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  2. Susan Foller
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  3. Mirjam Leeder
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  4. Katharina Leucht
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Correspondence to Marc-Oliver Grimm.

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Interessenkonflikt

M.-O. Grimm: Beratertätigkeit: AstraZeneca, Bristol Myers Squibb, Ipsen, MSD, Pfizer, Astellas Pharma, EUSA Pharma, Merck Serono, Roche Pharma AG, Eisai, Bayer Vital, Janssen, Gilead, Novartis; Honorare: AstraZeneca, Bristol Myers Squibb, MSD, Pfizer, lpsen, Merck Serono, EUSA Pharma, Janssen, Astellas Pharma, Takeda; Unterstützung für die Teilnahme an Sitzungen und/oder Konferenzen: Merck Serono, Brilstol Myers Squibb, Bayer, Pfizer, AstraZeneca. S. Foller: Beratertätigkeit: AstraZeneca, MSD, Merck Pfizer, Roche, Bristol-Myers Squibb; Referentenhonorare und/oder Kostenerstattungen (Reise- oder Übernachtungskosten, bezahlte Teilnehmergebühren): Bristol-Myers Squibb, AstraZeneca, MSD, Ipsen, Merck Pfizer. M. Leeder: Kostenerstattungen (Reise- oder Übernachtungskosten, bezahlte Teilnehmergebühren): Ipsen. K. Leucht: Medical Writing: Bristol Myers Squibb, Intuitive Surgical; Kostenerstattungen (Reise- oder Übernachtungskosten, bezahlte Teilnehmergebühren): Ipsen.

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

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Die Originalversion des Artikels wurde korrigiert: Tabelle 3 enthielt einen Fehler. Korrekt muss es in Zeile 4 heißen Sacituzumab-GOVITECAN + Pembrolizumab [17] (NCT03547973, TROPHY-U-01, Kohorte 3).

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Grimm, MO., Foller, S., Leeder, M. et al. Antikörper-Wirkstoff-Konjugate als neues Wirkprinzip in der Uroonkologie. Urologie 62, 679–684 (2023). https://doi.org/10.1007/s00120-023-02118-0

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