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Neue Studienprodukte in der onkologischen Immuntherapie

Novel study products in oncological immunotherapy

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Zusammenfassung

Die Entwicklung von Immuntherapeutika hat eine lange Geschichte in der Tumortherapie. Zytokine stellten über längere Zeit den elementaren Baustein der Immuntherapie von Tumoren dar. Ihre Wirksamkeit war beschränkt und nur bei sog. immunogenen Tumoren nachweisbar, wie z. B. beim malignen Melanom oder Nierenzellkarzinom. Das Ziel der Immuntherapie war das Erreichen einer anhaltenden Remission, was allerdings nur bei einer Minderheit der Patienten erzielt werden konnte. Mit Checkpoint-Inhibitoren ließ sich eine deutliche Verbesserung der klinischen Wirksamkeit und des Überlebens nachgeweisen. Aktuelle Studien erweitern das therapeutische Spektrum durch Inkorporation klassischer Medikamente der Tumortherapie, aber auch neuer Immuntherapeutika. Das Ziel ist die Entwicklung individueller Immuntherapien.

Abstract

The clinical development of immunotherapeutic agents has a long history in oncological treatment. Cytokines were the elementary foundations of immunotherapy for a long time; however, the effectiveness was limited and only detectable in so-called immunogenic tumors, such as malignant melanomas or renal cell carcinomas. The aim of immunotherapy is to achieve permanent remission, which, however, was only successful in the minority of patients. The introduction of checkpoint inhibitors resulted in a clear improvement in the clinical outcome of cancer patients as well as overall survival. Current clinical studies extend the spectrum of immunotherapy by incorporation of conventional medications for anti-tumor therapy as well as by novel immunotherapeutic drugs. The main goal is the development of individualized immunotherapy.

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Literatur

  1. Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12:252–264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hodi FS, O’Day SJ, Mcdermott DF, Weber RW, Sosman JA, Haanen JB et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723. doi:10.1056/NEJMoa1003466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O et al (2015) Pooled analysis of long-term survival data from phase II and phase III trials of Ipilimumab in unresectable or metastatic melanoma. J Clin Oncol ;33:1889–1894

    Article  PubMed  Google Scholar 

  4. Robert C, Schachter J, Long GV, Arance A, Grob J‑J, Mortier L et al (2015) Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med 372:2521–2532. doi:10.1056/NEJMoa1503093

    Article  CAS  PubMed  Google Scholar 

  5. Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D et al (2015) Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 372:2006–2017 (May)

    Article  PubMed  Google Scholar 

  6. Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L et al (2015) Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350:207–211

    Article  PubMed  PubMed Central  Google Scholar 

  7. Desrichard A, Snyder A, Chan TA (2015) Cancer neoantigens and applications for immunotherapy. Clin Cancer Res. doi:10.1158/1078-0432.CCR-14-3175

    PubMed  Google Scholar 

  8. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ et al (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124–128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gerlinger M, Horswell S, Larkin J, Rowan AJ, Salm MP, Varela I et al (2014) Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing. Nat Genet 46:225–233 (Feb)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. McGranahan N et al (2016) Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 14:1–11. doi:10.1126/science.aaf1490

    Google Scholar 

  11. Kleffel S, Posch C, Barthel SR, Mueller H, Schlapbach C, Guenova E et al (2015) Melanoma cell-intrinsic PD-1 receptor functions promote tumor growth. Cell 162:1242–1256 (Sep)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wolchok JD, Hoos A, O’Day S, Weber JS, Hamid O, Lebbe C et al (2009) Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 15:7412–7420

    Article  CAS  PubMed  Google Scholar 

  13. Hoos A, Wolchok JD, Humphrey RW, Hodi FS (2015) CCR 20th anniversary commentary: Immune-related response criteria-capturing clinical activity in immuno-oncology. Clin Cancer Res 21:4989–4991. doi:10.1158/1078-0432.CCR-14-3128

    Article  CAS  PubMed  Google Scholar 

  14. Hodi FS, Hwu W‑J, Kefford R, Weber JS, Daud A, Hamid O et al (2016) Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with Pembrolizumab. J Clin Oncol 34:1510–1517

    Article  PubMed  Google Scholar 

  15. George S, Motzer RJ, Hammers HJ, Redman BG, Kuzel TM, Tykodi SS et al (2016) Safety and efficacy of Nivolumab in patients with metastatic renal cell carcinoma treated beyond progression: A subgroup analysis of a randomized clinical trial. JAMA Oncol. doi:10.1001/jamaoncol.2016.0775

    Google Scholar 

  16. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S et al (2015) Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med 373:1803–1813. doi:10.1056/NEJMoa1510665

    Article  CAS  PubMed  Google Scholar 

  17. Prasad V, Kim C, Burotto M, Vandross A (2015) The strength of association between surrogate end points and survival in oncology. JAMA Intern Med 175:1389–1310

    Article  PubMed  Google Scholar 

  18. Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A et al (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial. Lancet 387:1–12

    Article  Google Scholar 

  19. Hughes T, Klairmont M, Broucek J, Iodice G, Basu S, Kaufman HL (2015) The prognostic significance of stable disease following high-dose interleukin-2 (IL-2) treatment in patients with metastatic melanoma and renal cell carcinoma. Cancer Immunol Immunother 64:459–465 (Apr)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Callea M, Albiges L, Gupta M, Cheng S‑C, Genega EM, Fay AP et al (2015) Differential expression of PD-L1 between primary and metastatic sites in clear-cell renal cell carcinoma. Cancer Immunol Res 3:1158–1164 (Oct)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gandini S, Massi D, Mandalà M (2016) PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis. Crit Rev Oncol Hematol 100:88–98. doi:10.1016/j.critrevonc.2016.02.001

    Article  PubMed  Google Scholar 

  22. Ferris RL, Blumenschein GR, Fayette J, Guigay J, Colevas, Licitra LF (2016) Further evaluations of nivolumab (nivo) versus investigator’s choice (IC) chemotherapy for recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): CheckMate 141. J Clin Oncol 34(suppl):abstr 6009

    Google Scholar 

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Correspondence to Viktor Grünwald MD.

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Interessenkonflikt

V. Grünwald erhält Honorare von den Firmen Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD) und Roche. Er ist als Berater für BMS und MSD tätig, wobei ihm die Reisekosten erstattet werden. Ferner erhält er Studienunterstützung von BMS, MSD und AstraZeneca.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Grünwald, V. Neue Studienprodukte in der onkologischen Immuntherapie. Forum 31, 398–401 (2016). https://doi.org/10.1007/s12312-016-0130-9

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  • DOI: https://doi.org/10.1007/s12312-016-0130-9

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