Das Medizinportal


Immuntherapien: Weiter auf dem Vormarsch

Barbara Mayer, Elfriede Nößner; München (S. 10-14)


  1. Couzin-Frankel J, Science 2013;342(6165):1432-1433
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  5. Kantoff PW, Higano CS, et al. N Engl J Med 2010;363:411-22.
  6. Wolchok JD et al. N Engl J Med 2013;369:122-33
  7. Choudhury and Nakamura, Cancer Sci 2015,Dec. 17
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Aktuelle Entwicklungen bei Checkpoint-Inhibitoren

I. Cosgarea, B. Schilling; Duisburg-Essen (S. 16-18)


  1. Coulie, P.G., et al., Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer, 2014. 14(2): p. 135-46.
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  4. Balch, C.M., et al., Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol, 2009. 27(36): p. 6199-206.
  5. Topalian, S.L., C.G. Drake, and D.M. Pardoll, Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell, 2015. 27(4): p. 450-61.
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  7. Spranger, S., et al., Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med, 2013. 5(200): p. 200ra116.
  8. Robert, C., et al., Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med, 2015. 372(4): p. 320-30.
  9. Ribas, A., et al., Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol, 2015. 16(8): p. 908-18.
  10. Robert, C., et al., Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med, 2015.
  11. Brahmer, J., et al., Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med, 2015. 373(2): p. 123-35.
  12. Motzer, R.J., et al., Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med, 2015. 373(19): p. 1803-13.
  13. Buisseret , L., et al., 14P - KEYNOTE-012: A phase Ib study of pembrolizumab (MK-3475) in patients (pts) with metastatic triple-negative breast cancer (mTNBC). Annals of Oncology (2015) 26 (suppl_3): 6-9. 10.1093/annonc/mdv115
  14. Powles, T., et al., MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature, 2014. 515(7528): p. 558-62.
  15. Berger, R., et al., Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin Cancer Res, 2008. 14(10): p. 3044-51.
  16. Westin, J.R., et al., Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial. Lancet Oncol, 2014. 15(1): p. 69-77.
  17. Ansell, S.M., et al., PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma. N Engl J Med, 2014.
  18. Postow, M.A., et al., Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma. N Engl J Med, 2015.
  19. Larkin, J., et al., Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med, 2015. 373(1): p. 23-34.
  20. Carbognin, L., et al., Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers. PLoS One, 2015. 10(6): p. e0130142.
  21. van Rooij, N., et al., Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J Clin Oncol, 2013. 31(32): p. e439-42.
  22. Van Allen, E.M., et al., Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science, 2015. 350(6257): p. 207-11.
  23. Kaehler, K.C., et al., Update on immunologic therapy with anti-CTLA-4 antibodies in melanoma: identification of clinical and biological response patterns, immune-related adverse events, and their management. Semin Oncol, 2010. 37(5): p. 485-98.

Immuntherapie mit Bi- oder Multispezifischen Antikörpern

Th. Köhnke, Chr. Krupka, M. Subklewe; München (S. 19-22)


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  14. Ott MG, Marmé F, Moldenhauer G, Lindhofer H, Hennig M, Spannagl R, et al. Humoral response to catumaxomab correlates with clinical outcome: results of the pivotal phase II/III study in patients with malignant ascites. Int J Cancer 2012;130:2195–203. doi:10.1002/ijc.26258.
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  20. Krupka C, Kufer P, Kischel R, Zugmaier G, Lichtenegger FS, Köhnke T, et al. Blockade of the PD-1/PD-L1 axis augments lysis of AML cells by the CD33/CD3-BiTE® antibody construct AMG 330: reversing a T-cell induced immune escape mechanism. Leukemia 2015. doi:10.1038/leu.2015.214.
  21. Vela M, Aris M, Llorente M, Garcia-Sanz JA, Kremer L. Chemokine receptor-specific antibodies in cancer immunotherapy: achievements and challenges. Front Immunol 2015;6:12. doi:10.3389/fimmu.2015.00012.
  22. Papadopoulos KP, Isaacs R, Bilic S, Kentsch K, Huet HA, Hofmann M, et al. Unexpected hepatotoxicity in a phase I study of TAS266, a novel tetravalent agonistic Nanobody® targeting the DR5 receptor. Cancer Chemotherapy and Pharmacology 2015:1–9. doi:10.1007/s00280-015-2712-0.
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T-Zell-Therapien: aktueller Stand der Entwicklung

Richard Klar, Angela Krackhardt;  München (S. 24-26)


  1. Fridman, W.H., et al., The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer, 2012. 12(4): p. 298-306.
  2. Rizvi, N.A., et al., Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science, 2015. 348(6230): p. 124-8.
  3. Snyder, A., et al., Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med, 2014. 371(23): p. 2189-99.
  4. Hinrichs, C.S. and S.A. Rosenberg, Exploiting the curative potential of adoptive T-cell therapy for cancer. Immunol Rev, 2014. 257(1): p. 56-71.
  5. Joseph, R.W., et al., Impact of clinical and pathologic features on tumor-infiltrating lymphocyte expansion from surgically excised melanoma metastases for adoptive T-cell therapy. Clin Cancer Res, 2011. 17(14): p. 4882-91.
  6. Maher, J., et al., Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta /CD28 receptor. Nat Biotechnol, 2002. 20(1): p. 70-5.
  7. Porter, D.L., et al., Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med, 2011. 365(8): p. 725-33.
  8. Maude, S.L., et al., Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med, 2014. 371(16): p. 1507-17.
  9. van der Stegen, S.J., M. Hamieh, and M. Sadelain, The pharmacology of second-generation chimeric antigen receptors. Nat Rev Drug Discov, 2015. 14(7): p. 499-509.
  10. Kershaw, M.H., J.A. Westwood, and P.K. Darcy, Gene-engineered T cells for cancer therapy. Nat Rev Cancer, 2013. 13(8): p. 525-41.
  11. Di Stasi, A., et al., Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med, 2011. 365(18): p. 1673-83.
  12. Beatty, G.L., et al., Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res, 2014. 2(2): p. 112-20.
  13. Kloss, C.C., et al., Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat Biotechnol, 2013. 31(1): p. 71-5.
  14. Morgan, R.A., et al., Cancer regression in patients after transfer of genetically engineered lymphocytes. Science, 2006. 314(5796): p. 126-9.
  15. Johnson, L.A., et al., Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood, 2009. 114(3): p. 535-46.
  16. Robbins, P.F., et al., Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol, 2011. 29(7): p. 917-24.
  17. Linnemann, C., et al., High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4+ T cells in human melanoma. Nat Med, 2015. 21(1): p. 81-5.
  18. Klar, R., et al., Therapeutic targeting of naturally presented myeloperoxidase-derived HLA peptide ligands on myeloid leukemia cells by TCR-transgenic T cells. Leukemia, 2014. 28(12): p. 2355-66.
  19. Cameron, B.J., et al., Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. Sci Transl Med, 2013. 5(197): p. 197ra103.
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  21. Chen, D.S. and I. Mellman, Oncology meets immunology: the cancer-immunity cycle. Immunity, 2013. 39(1): p. 1-10.
  22. Mahoney, K.M., P.D. Rennert, and G.J. Freeman, Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov, 2015. 14(8): p. 561-84.
  23. Howe, S.J., et al., Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest, 2008. 118(9): p. 3143-50.
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