Der Internist

, Volume 56, Issue 8, pp 907–917 | Cite as

Immunologische Tumortherapie

CME Zertifizierte Fortbildung
First Online:

Zusammenfassung

Grundsätzlich kann das Immunsystem Tumorzellen erkennen und eliminieren. Trotzdem gelingt es Tumorzellen, der Immunüberwachung zu entgehen. Grundgedanke der Immuntherapie ist es, das körpereigene Abwehrsystem so zu aktivieren, dass es maligne Zellen wieder erkennt und beseitigt. In den letzten Jahren wurden vielfältige immunonkologische Therapiestrategien entwickelt, z. B. bi- und multispezifische oder immunregulatorische Antikörper, genmodifizierte T-Lymphozyten oder Tumorvakzinen. Einige Therapeutika sind bereits zugelassen, andere in klinischen Studien zugänglich. Dieser Beitrag stellt die aktuell aussichtsreichen Ansätze der Immunonkologie und deren immunbiologische Grundlagen vor. Derzeit besteht noch erheblicher Forschungsbedarf – so müssen Biomarker für zielgerichtete Therapiestrategien etabliert und die Langzeitwirkung sowie Kombinierbarkeit von Therapien untersucht werden. Dennoch wird die Immunonkologie in wenigen Jahren fester Bestandteil onkologischer Behandlungskonzepte sein.

Schlüsselwörter

Tumorvakzinen Immunmodulation Adoptiver Transfer immunologischer Effektoren Immuncheckpoint, Inhibition Chimäre Antigenrezeptoren 

Immunological tumor therapy

Abstract

Tumor cells could fundamentally be recognized and eliminated by the immune system but malignant cells are able to escape the immune surveillance system. The idea of immunotherapy of cancer is to activate, modulate and amplify the host immune response or to genetically equip the immune repertoire of patients with anti-tumor specificities and effectors. In recent years, a variety of promising immunotherapy strategies have been developed, such as bispecific, multispecific and immunoregulatory antibodies, gene-modified T lymphocytes and tumor vaccines. Some drugs have already been approved and others are available for patients in clinical trials. This article presents the current anti-tumor immune strategies and their molecular basis. Even though further research is needed in some areas, such as the establishment of biomarkers for targeted therapy, duration of therapeutic activity and compatibility of combined strategies, cancer immunotherapy is likely to be a key component in oncological treatment concepts in the very near future.

Keywords

Cancer vaccines Immunomodulation Immunological effectors, adoptive transfer Immune checkpoint, blockade Antigen receptors, chimeric 
This is a preview of subscription content, log in to check access.

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt. K. Dietrich und M. Theobald geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Maus MV, Grupp SA, Porter DL et al (2014) Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood 123:2625–2635PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Palucka K, Banchereau J (2012) Cancer immunotherapy via dendritic cells. Nat Rev Cancer 12:265–277PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Kantoff PW, Higano CS, Shore ND et al (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363:411–422Google Scholar
  4. 4.
    Weber JS (2014) Current perspectives on immunotherapy. Semin Oncol 41(Suppl 5):S14–S29PubMedCrossRefGoogle Scholar
  5. 5.
    Disis ML (2014) Mechanism of action of immunotherapy. Semin Oncol 41(Suppl 5):S3–S13PubMedCrossRefGoogle Scholar
  6. 6.
    Browning MJ (2013) Antigen presenting cell/tumor cell fusion vaccines for cancer immunotherapy. Hum Vaccin Immunother 9:1545–1548PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Chiang CL, Kandalaft LE, Coukos G (2011) Adjuvants for enhancing the immunogenicity of whole tumor cell vaccines. Int Rev Immunol 30:150–182PubMedCrossRefGoogle Scholar
  8. 8.
    Makkouk A, Weiner GJ (2015) Cancer immunotherapy and breaking immune tolerance: new approaches to an old challenge. Cancer Res 75:5–10PubMedCrossRefGoogle Scholar
  9. 9.
    Mellman I, Coukos G, Dranoff G (2011) Cancer immunotherapy comes of age. Nature 480:480–489PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Sahin U, Karikó K, Türeci Ö (2014) mRNA-based therapeutics – developing a new class of drugs. Nat Rev Drug Discov 13:759–780PubMedCrossRefGoogle Scholar
  11. 11.
    Kreiter S, Vormehr M, Roemer N van de et al (2015) Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature 520:692–696PubMedCrossRefGoogle Scholar
  12. 12.
    Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12:252–264PubMedCrossRefGoogle Scholar
  13. 13.
    Hodi FS, O’Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723Google Scholar
  14. 14.
    Hamid O, Robert C, Daud A et al (2013) Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 369:134–144Google Scholar
  15. 15.
    Robert C, Long GV, Brady B et al (2015) Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372:320–330Google Scholar
  16. 16.
    Curti BD, Kovacsovics-Bankowski M, Morris N et al (2013) OX40 is a potent immune-stimulating target in late-stage cancer patients. Cancer Res 73:7189–7198PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Vanneman M, Dranoff G (2012) Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer 12:237–251PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Rizvi NA, Hellmann MD, Snyder A et al (2015) Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124–128PubMedCrossRefGoogle Scholar
  19. 19.
    Duong CMP, Yong CSM, Kershaw MH et al (2015) Cancer immunotherapy utilizing gene-modified T cells: from the bench to the clinic. Mol Immunol (im Druck). http://dx.doi.org/10.1016/j.molimm.2014.12.009Google Scholar
  20. 20.
    Weidle UH, Kontermann RE, Brinkmann U (2014) Tumor-antigen-binding bispecific antibodies for cancer treatment. Semin Oncol 41:653–660PubMedCrossRefGoogle Scholar
  21. 21.
    Topp MS, Gökbuget N, Stein AS et al (2015) Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol 16:57–66PubMedCrossRefGoogle Scholar
  22. 22.
    Huehls AM, Coupet TA, Sentman CL (2015) Bispecific T-cell engagers for cancer immunotherapy. Immunol Cell Biol 93:290–296PubMedCrossRefGoogle Scholar
  23. 23.
    Topalian SL, Solomon D, Avis FP et al (1988) Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study. J Clin Oncol 6:839–853Google Scholar
  24. 24.
    Dudley ME, Yang JC, Sherry R et al (2008) Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol 26:5233–5239Google Scholar
  25. 25.
    Rosenberg SA, Yang JC, Sherry RM et al (2011) Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res 17:4550–4557PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Morgan RA, Dudley ME, Wunderlich JR et al (2006) Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314:126–129PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Stanislawski T, Voss RH, Lotz C et al (2001) Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer. Nat Immunol 2:962–970PubMedCrossRefGoogle Scholar
  28. 28.
    Parkhurst MR, Joo J, Riley JP et al (2009) Characterization of genetically modified T-cell receptors that recognize the CEA:691–699 peptide in the context of HLA-A2.1 on human colorectal cancer cells. Clin Cancer Res 15:169–180PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Robbins PF, Morgan RA, Feldman SA et al (2011) Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 29:917–924Google Scholar
  30. 30.
    Kuball J, Schmitz FW, Voss RH et al (2005) Cooperation of human tumor-reactive CD4+ and CD8+ T cells after redirection of their specificity by a high-affinity p53A2.1-specific TCR. Immunity 22:117–129PubMedCrossRefGoogle Scholar
  31. 31.
    Kershaw MH, Westwood JA, Slaney CY et al (2014) Clinical application of genetically modified T cells in cancer therapy. Clin Transl Immunology 3:e16PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.III. Medizinische Klinik und PoliklinikUniversitätsmedizin MainzMainzDeutschland

Personalised recommendations