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Vakzinierungen in der Therapie des Mammakarzinoms

Stand klinischer Studien

Vaccination in the therapy of breast cancer

  • Update Onkologie
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Der Onkologe Aims and scope

Zusammenfassung

Für Brustkrebspatientinnen wurden therapeutische Vakzinierungen bisher selten und dann in Pilot- bzw. Phase-I-Studien beim metastasiertem Mammakarzinom erprobt. Dabei kam international ein breites Spektrum verschiedener Strategien zum Einsatz: tumorzellbasierte Vakzinen, antigenspezifische Impfungen (definierte Peptid-, RNA- und DNA-Vakzinen) sowie Vakzinierungen gegen Karbohydrate. Allen Ansätzen ist gemeinsam, dass sie ein tolerierbares Nebenwirkungsprofil hatten und in der palliativen Situation zumindest vereinzelt zur Stabilisierung der Erkrankung beitrugen. In aktuelleren Studien wurde anhand diverser immunologischer Parameter gezeigt, dass die Induktion tumorspezifischer T-Zellen und/oder Antikörper in Mammakarzinompatientinnen prinzipiell möglich ist. Da es für die Validierung antitumoraler Immunreaktionen jedoch keine verbindlichen Standards gibt und da klinische Endpunkte meist nur als sekundäre Zielkriterien erfasst wurden, ist es derzeit noch nicht möglich, induzierte Immunreaktionen als Surrogatparameter für die therapeutische Wirksamkeit verschiedener Impfstrategien zu werten. In der metastasierten Situation führte die Zusammensetzung, Ausprägung und Persistenz der induzierten Immunrantwort noch nicht zu einem dauerhaften klinischen Benefit. Jedoch zeigte eine erste prospektiv kontrollierte Vakzinierungsstudie mit insgesamt 53 Patientinnen in der Adjuvanz, dass nodalpositive, Her-2/neu+ Hochrisikopatientinnen von der Vakzination mit Her-2/neu-abgeleiteten Peptiden profitierten und die Rückfallrate reduziert wurde. Zur Optimierung immuntherapeutischer Strategien sollen Kombinationen verschiedener Ansätze führen, die multiple Targetstrukturen erreichen und multiple immunologische Effektorarme aktivieren können. Zudem müssen Patientenkollektive definiert werden, die tatsächlich von Immuntherapien profitieren können.

Abstract

Therapeutic vaccinations have seldom been tested in patients with breast cancer and only in pilot or phase I trials involving metastatic breast cancer. A wide spectrum of different strategies has been applied internationally in this area including tumor-based vaccines, antigen-specific vaccinations (defined peptide-, RNA-, and DNA-vaccines), and vaccinations against carbohydrates. These strategies all have one thing in common, they have been shown to have a profile of side effects that is tolerable and in the palliative situation, in certain cases, contributed to stabilization of the disease. By applying diverse immunological parameters, current investigations have demonstrated that the induction of tumor-specific T cells and/or antibodies in patients with breast cancer is, in principle, possible. However, as there are no binding standards for validating anti-tumor immune reactions and as clinical end points are usually only recorded as secondary target criteria, it is not currently possible to classify induced immune reactions as a surrogate parameter for the therapeutic effectiveness of different vaccination strategies. In situations involving metastasis, the composition, expression and persistence of the induced immune response has not yet led to a long-lasting clinical benefit. Nevertheless, the first prospective controlled vaccination study involving 53 patients revealed that nodal-positive, Her-2/neu+ high-risk patients profited from vaccination with Her-2/neu-derived peptides and that recidivism was reduced. The combination of various approaches should lead to the optimization of immunotherapeutic strategies. These combinations should reach multiple target structures and should activate multiple immunological effector arms. The patient collectives that can actually profit from immunotherapies must, however, still be defined.

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  1. Frauenklinik der Eberhard-Karls-Universität Tübingen

    B. Gückel

  2. Frauenklinik der Eberhard-Karls-Universität Tübingen, Calwerstraße 7, 72 076, Tübingen

    B. Gückel

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Gückel, B. Vakzinierungen in der Therapie des Mammakarzinoms. Onkologe 12, 253–262 (2006). https://doi.org/10.1007/s00761-005-0999-x

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