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DOI: 10.1055/s-0043-121594
Immunotherapy – The New Era of Oncology
Artikel in mehreren Sprachen: deutsch | EnglishPublikationsverlauf
Publikationsdatum:
22. März 2018 (online)
![](https://www.thieme-connect.de/media/lro/2018S01/lookinside/thumbnails/4982227_10-1055-s-0043-121594_en-1.jpg)
Abstract
In the field of immunotherapy, essential progress was achieved over the past years partially demonstrating long lasting therapeutic responses in different tumor entities. A better understanding of the interactions between the tumor and the immune system as well as the integration of immunotherapeutic approaches into clinical routine were the foundations for this development. The different approaches intervene on multiple levels of the immune response and directly or indirectly mount the patient‘s own immune defense against tumor cells. Immunotherapeutic approaches are represented by cytokine therapies, vaccinations, the use of oncolytic viruses and monoclonal antibody therapies as well as adoptive cell transfer strategies.
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Literatur
- 1 Coley II WB. Contribution to the Knowledge of Sarcoma. Annals of surgery 1891; 14: 199-220
- 2 Hodi FS, O'Day SJ, McDermott DF. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363: 711-723
- 3 Topalian SL, Hodi FS, Brahmer JR. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366: 2443-2454
- 4 Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science (New York, NY) 2013; 342: 1432-1433
- 5 Mantovani A, Sozzani S, Locati M. et al. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends in immunology 2002; 23: 549-555
- 6 Komohara Y, Jinushi M, Takeya M. Clinical significance of macrophage heterogeneity in human malignant tumors. Cancer science 2014; 105: 1-8
- 7 Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science (New York, NY) 2015; 348: 62-68
- 8 Keir ME, Butte MJ, Freeman GJ. et al. PD-1 and its ligands in tolerance and immunity. Annual review of immunology 2008; 26: 677-704
- 9 Dunn GP, Bruce AT, Ikeda H. et al. Cancer immunoediting: from immunosurveillance to tumor escape. Nature immunology 2002; 3: 991-998
- 10 Burnet FM. The concept of immunological surveillance. Progress in experimental tumor research 1970; 13: 1-27
- 11 Mittal D, Gubin MM, Schreiber RD. et al. New insights into cancer immunoediting and its three component phases — elimination, equilibrium and escape. Current opinion in immunology 2014; 27: 16-25
- 12 Teng MW, Vesely MD, Duret H. et al. Opposing roles for IL-23 and IL-12 in maintaining occult cancer in an equilibrium state. Cancer Res 2012; 72: 3987-3996
- 13 Grandis JR, Falkner DM, Melhem MF. et al. Human leukocyte antigen class I allelic and haplotype loss in squamous cell carcinoma of the head and neck: clinical and immunogenetic consequences. Clin Cancer Res 2000; 6: 2794-2802
- 14 Mizukami Y, Kono K, Maruyama T. et al. Downregulation of HLA Class I molecules in the tumour is associated with a poor prognosis in patients with oesophageal squamous cell carcinoma. Br J Cancer 2008; 99: 1462-1467
- 15 Ogino T, Shigyo H, Ishii H. et al. HLA class I antigen down-regulation in primary laryngeal squamous cell carcinoma lesions as a poor prognostic marker. Cancer Res 2006; 66: 9281-9289
- 16 Goeppert B, Frauenschuh L, Zucknick M. et al. Major histocompatibility complex class I expression impacts on patient survival and type and density of immune cells in biliary tract cancer. Br J Cancer 2015; 113: 1343-1349
- 17 Zhang J, Xu Z, Zhou X. et al. Loss of expression of MHC class I-related chain A (MICA) is a frequent event and predicts poor survival in patients with hepatocellular carcinoma. International journal of clinical and experimental pathology 2014; 7: 3123-3131
- 18 Watson NF, Ramage JM, Madjd Z. et al. Immunosurveillance is active in colorectal cancer as downregulation but not complete loss of MHC class I expression correlates with a poor prognosis. Int J Cancer 2006; 118: 6-10
- 19 Wang JH, Bi XW, Li PF. et al. Overexpression of MYC and BCL2 Predicts Poor Prognosis in Patients with Extranodal NK/T-cell Lymphoma, Nasal Type. Journal of Cancer 2017; 8: 793-800
- 20 Wang T, Niu G, Kortylewski M. et al. Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nature medicine 2004; 10: 48-54
- 21 Gastman BR, Atarshi Y, Reichert TE. et al. Fas ligand is expressed on human squamous cell carcinomas of the head and neck, and it promotes apoptosis of T lymphocytes. Cancer Res 1999; 59: 5356-5364
- 22 Lu P, Weaver VM, Werb Z. The extracellular matrix: a dynamic niche in cancer progression. The Journal of cell biology 2012; 196: 395-406
- 23 Paszek MJ, Zahir N, Johnson KR. et al. Tensional homeostasis and the malignant phenotype. Cancer Cell 2005; 8: 241-254
- 24 Mott JD, Werb Z. Regulation of matrix biology by matrix metalloproteinases. Current opinion in cell biology 2004; 16: 558-564
- 25 Levental KR, Yu H, Kass L. et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 2009; 139: 891-906
- 26 Pickup MW, Mouw JK, Weaver VM. The extracellular matrix modulates the hallmarks of cancer. EMBO reports 2014; 15: 1243-1253
- 27 Meyaard L. The inhibitory collagen receptor LAIR-1 (CD305). Journal of leukocyte biology 2008; 83: 799-803
- 28 Vesely MD, Kershaw MH, Schreiber RD. et al. Natural innate and adaptive immunity to cancer. Annual review of immunology 2011; 29: 235-271
- 29 Fox SB, Gasparini G, Harris AL. Angiogenesis: pathological, prognostic, and growth-factor pathways and their link to trial design and anticancer drugs. The Lancet Oncology 2001; 2: 278-289
- 30 Fayette J, Soria JC, Armand JP. Use of angiogenesis inhibitors in tumour treatment. Eur J Cancer 2005; 41: 1109-1116
- 31 Li H, Fan X, Houghton J. Tumor microenvironment: the role of the tumor stroma in cancer. J Cell Biochem 2007; 101: 805-815
- 32 Xing F, Saidou J, Watabe K. Cancer associated fibroblasts (CAFs) in tumor microenvironment. Frontiers in bioscience: a journal and virtual library 15: 166-179
- 33 Koukourakis MI, Giatromanolaki A, Harris AL. et al. Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma. Cancer Res 2006; 66: 632-637
- 34 Thomasset N, Lochter A, Sympson CJ. et al. Expression of autoactivated stromelysin-1 in mammary glands of transgenic mice leads to a reactive stroma during early development. Am J Pathol 1998; 153: 457-467
- 35 Herrera M, Herrera A, Dominguez G. et al. Cancer-associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients. Cancer science 2013; 104: 437-444
- 36 Comito G, Giannoni E, Segura CP. et al. Cancer-associated fibroblasts and M2-polarized macrophages synergize during prostate carcinoma progression. Oncogene 2014; 33: 2423-2431
- 37 Chaudhary B, Elkord E. Regulatory T Cells in the Tumor Microenvironment and Cancer Progression: Role and Therapeutic Targeting. Vaccines 2016; 4:
- 38 Shevach EM. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity 2009; 30: 636-645
- 39 Elkord E, Alcantar-Orozco EM, Dovedi SJ. et al. T regulatory cells in cancer: recent advances and therapeutic potential. Expert opinion on biological therapy 2010; 10: 1573-1586
- 40 Ghiringhelli F, Menard C, Terme M. et al. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J Exp Med 2005; 202: 1075-1085
- 41 Jie HB, Gildener-Leapman N, Li J. et al. Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients. Br J Cancer 2013; 109: 2629-2635
- 42 Ostrand-Rosenberg S, Sinha P. Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 2009; 182: 4499-4506
- 43 Srivastava MK, Sinha P, Clements VK. et al. Myeloid-derived Suppressor Cells Inhibit T Cell Activation by Depleting Cystine and Cysteine. Cancer Res 2010; 70: 68-77
- 44 Rodriguez PC, Quiceno DG, Zabaleta J. et al. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res 2004; 64: 5839-5849
- 45 Barnie PA, Zhang P, Lv H. et al. Myeloid-derived suppressor cells and myeloid regulatory cells in cancer and autoimmune disorders. Experimental and therapeutic medicine 2017; 13: 378-388
- 46 Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature 2013; 496: 445-455
- 47 Quail DF, Joyce JA. Molecular Pathways: Deciphering Mechanisms of Resistance to Macrophage-Targeted Therapies. Clin Cancer Res 2017; 23: 876-884
- 48 Solinas G, Germano G, Mantovani A. et al. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. Journal of leukocyte biology 2009; 86: 1065-1073
- 49 Allavena P, Sica A, Solinas G. et al. The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages. Critical reviews in oncology/hematology 2008; 66: 1-9
- 50 Reya T, Morrison SJ, Clarke MF. et al. Stem cells, cancer, and cancer stem cells. Nature 2001; 414: 105-111
- 51 Yoo MH, Hatfield DL. The cancer stem cell theory: is it correct?. Molecules and cells 2008; 26: 514-516
- 52 Chen J, Li Y, Yu TS. et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 2012; 488: 522-526
- 53 Tang C, Ang BT, Pervaiz S. Cancer stem cell: target for anti-cancer therapy. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 2007; 21: 3777-3785
- 54 Auffinger B, Tobias AL, Han Y. et al. Conversion of differentiated cancer cells into cancer stem-like cells in a glioblastoma model after primary chemotherapy. Cell Death Differ 2014; 21: 1119-1131
- 55 Bhatia A, Kumar Y. Cancer stem cells and tumor immunoediting: putting two and two together. Expert Rev Clin Immunol 2016; 12: 605-607
- 56 Wei J, Barr J, Kong LY. et al. Glioblastoma cancer-initiating cells inhibit T-cell proliferation and effector responses by the signal transducers and activators of transcription 3 pathway. Molecular cancer therapeutics 2010; 9: 67-78
- 57 Anestakis D, Petanidis S, Kalyvas S. et al. Mechanisms and Αpplications of Ιnterleukins in Cancer Immunotherapy. International journal of molecular sciences 2015; 16: 1691-1710
- 58 Amedei A, Prisco D, MM DE. The use of cytokines and chemokines in the cancer immunotherapy. Recent patents on anti-cancer drug discovery 2013; 8: 126-142
- 59 Morgan DA, Ruscetti FW, Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science (New York, NY) 1976; 193: 1007-1008
- 60 Baluna R, Vitetta ES. Vascular leak syndrome: a side effect of immunotherapy. Immunopharmacology 1997; 37: 117-132
- 61 Rosenberg SA, Yang JC, White DE. et al. Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2: identification of the antigens mediating response. Annals of surgery 1998; 228: 307-319
- 62 Sim GC, Radvanyi L. The IL-2 cytokine family in cancer immunotherapy. Cytokine & growth factor reviews 2014; 25: 377-390
- 63 Belperio JA, Keane MP, Arenberg DA. et al. CXC chemokines in angiogenesis. Journal of leukocyte biology 2000; 68: 1-8
- 64 Balkwill F. Cancer and the chemokine network. Nature reviews Cancer 2004; 4: 540-550
- 65 Yoshie O, Matsushima K. CCR4 and its ligands: from bench to bedside. International immunology 2015; 27: 11-20
- 66 Taeger G, Grabellus F, Podleska LE. et al. Effectiveness of regional chemotherapy with TNF-alpha/melphalan in advanced soft tissue sarcoma of the extremities. International journal of hyperthermia: the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 2008; 24: 193-203
- 67 van Horssen R, Ten Hagen TL, Eggermont AM. TNF-alpha in cancer treatment: molecular insights, antitumor effects, and clinical utility. The oncologist 2006; 11: 397-408
- 68 Parker BS, Rautela J, Hertzog PJ. Antitumour actions of interferons: implications for cancer therapy. Nature reviews Cancer 2016; 16: 131-144
- 69 Srivastava S, Koch MA, Pepper M. et al. Type I interferons directly inhibit regulatory T cells to allow optimal antiviral T cell responses during acute LCMV infection. J Exp Med 2014; 211: 961-974
- 70 Zoglmeier C, Bauer H, Norenberg D. et al. CpG blocks immunosuppression by myeloid-derived suppressor cells in tumor-bearing mice. Clin Cancer Res 2011; 17: 1765-1775
- 71 Greiner JW, Hand PH, Noguchi P. et al. Enhanced expression of surface tumor-associated antigens on human breast and colon tumor cells after recombinant human leukocyte alpha-interferon treatment. Cancer Res 1984; 44: 3208-3214
- 72 Abiko K, Matsumura N, Hamanishi J. et al. IFN-gamma from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer. Br J Cancer 2015; 112: 1501-1509
- 73 Zaidi MR, Merlino G. The two faces of interferon-gamma in cancer. Clin Cancer Res 2011; 17: 6118-6124
- 74 Rozati S, Naef L, Levesque MP. et al. Real-life experience with pegylated interferon and conventional interferon in adjuvant melanoma therapy. Journal of immunotherapy (Hagerstown, Md: 1997) 2013; 36: 52-56
- 75 Eggermont AM, Suciu S, Testori A. et al. Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma. J Clin Oncol 2012; 30: 3810-3818
- 76 von Tresckow B, Morschhauser F, Ribrag V. et al. An Open-Label, Multicenter, Phase I/II Study of JNJ-40346527, a CSF-1 R Inhibitor, in Patients with Relapsed or Refractory Hodgkin Lymphoma. Clin Cancer Res 2015; 21: 1843-1850
- 77 Ries CH, Cannarile MA, Hoves S. et al. Targeting tumor-associated macrophages with anti-CSF-1 R antibody reveals a strategy for cancer therapy. Cancer Cell 2014; 25: 846-859
- 78 Waller EK. The role of sargramostim (rhGM-CSF) as immunotherapy. The oncologist 2007; 12 (Suppl. 02) 22-26
- 79 Yan WL, Shen KY, Tien CY. et al. Recent progress in GM-CSF-based cancer immunotherapy. Immunotherapy 2017; 9: 347-360
- 80 Okamoto M, Oshikawa T, Tano T. et al. Mechanism of anticancer host response induced by OK-432, a streptococcal preparation, mediated by phagocytosis and Toll-like receptor 4 signaling. Journal of immunotherapy (Hagerstown, Md: 1997) 2006; 29: 78-86
- 81 Goldinger SM, Dummer R, Baumgaertner P. et al. Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8(+) T-cell responses in melanoma patients. European journal of immunology 2012; 42: 3049-3061
- 82 Lichty BD, Breitbach CJ, Stojdl DF. et al. Going viral with cancer immunotherapy. Nature reviews Cancer 2014; 14: 559-567
- 83 Andtbacka RH, Kaufman HL, Collichio F. et al. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol 2015; 33: 2780-2788
- 84 Kaufman HL, Andtbacka RHI, Collichio FA. et al. Durable response rate as an endpoint in cancer immunotherapy: insights from oncolytic virus clinical trials. Journal for immunotherapy of cancer 2017; 5: 72
- 85 Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975; 256: 495-497
- 86 Ecker DM, Jones SD, Levine HL. The therapeutic monoclonal antibody market. mAbs 2015; 7: 9-14
- 87 Lanitis E, Dangaj D, Hagemann IS et al. Primary Human Ovarian Epithelial Cancer Cells Broadly Express HER2 at Immunologically-Detectable Levels. PLoS One 2012; 7:
- 88 Wang Z. ErbB Receptors and Cancer. Methods in molecular biology (Clifton, NJ) 2017; 1652: 3-35
- 89 Francisco LM, Salinas VH, Brown KE. et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med 2009; 206: 3015-3029
- 90 Brahmer JR, Drake CG, Wollner I. et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010; 28: 3167-3175
- 91 Lipson EJ, Sharfman WH, Drake CG. et al. Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clin Cancer Res 2013; 19: 462-468
- 92 Hodi FS, Mihm MC, Soiffer RJ. et al. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci U S A 2003; 100: 4712-4717
- 93 Giuroiu I, Weber J. Novel Checkpoints and Cosignaling Molecules in Cancer Immunotherapy. Cancer journal (Sudbury, Mass) 2017; 23: 23-31
- 94 Ma SR, Deng WW, Liu JF. et al. Blockade of adenosine A2A receptor enhances CD8+ T cells response and decreases regulatory T cells in head and neck squamous cell carcinoma. Molecular cancer 2017; 16: 99
- 95 Chen YW, Tekle C, Fodstad O. The immunoregulatory protein human B7H3 is a tumor-associated antigen that regulates tumor cell migration and invasion. Current cancer drug targets 2008; 8: 404-413
- 96 Spodzieja M, Lach S, Iwaszkiewicz J. et al. Design of short peptides to block BTLA/HVEM interactions for promoting anticancer T-cell responses. PLoS One 2017; 12: e0179201
- 97 Muntasell A, Ochoa MC, Cordeiro L. et al. Targeting NK-cell checkpoints for cancer immunotherapy. Current opinion in immunology 2017; 45: 73-81
- 98 Andrews LP, Marciscano AE, Drake CG. et al. LAG3 (CD223) as a cancer immunotherapy target. Immunological reviews 2017; 276: 80-96
- 99 Zhu C, Anderson AC, Kuchroo VK. TIM-3 and its regulatory role in immune responses. Current topics in microbiology and immunology 2011; 350: 1-15
- 100 Kakavand H, Jackett LA, Menzies AM. et al. Negative immune checkpoint regulation by VISTA: a mechanism of acquired resistance to anti-PD-1 therapy in metastatic melanoma patients. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 2017; DOI: 10.1038/modpathol.2017.89.
- 101 Lee LY, Garland SM. Human papillomavirus vaccination: the population impact. F1000Research 2017; 6: 866
- 102 Hampton T. Nobel Prize honors HIV, HPV discoveries. Jama 2008; 300: 2109
- 103 Ramqvist T, Dalianis T. Oropharyngeal Cancer Epidemic and Human Papillomavirus. Emerging Infectious Diseases 2010; 16: 1671-1677
- 104 Osazuwa-Peters N. Human papillomavirus (HPV), HPV-associated oropharyngeal cancer, and HPV vaccine in the United States – do we need a broader vaccine policy?. Vaccine 2013; 31: 5500-5505
- 105 van der Burg SH, Arens R, Ossendorp F. et al. Vaccines for established cancer: overcoming the challenges posed by immune evasion. Nature reviews Cancer 2016; 16: 219-233
- 106 Kenter GG, Welters MJ, Valentijn AR. et al. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med 2009; 361: 1838-1847
- 107 van Poelgeest MI, Welters MJ, Vermeij R. et al. Vaccination against Oncoproteins of HPV16 for Noninvasive Vulvar/Vaginal Lesions: Lesion Clearance Is Related to the Strength of the T-Cell Response. Clin Cancer Res 2016; 22: 2342-2350
- 108 Welters MJ, Kenter GG, de Vos van Steenwijk PJ. et al. Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses. Proc Natl Acad Sci U S A 2010; 107: 11895-11899
- 109 Czerniecki BJ, Koski GK, Koldovsky U. et al. Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion. Cancer Res 2007; 67: 1842-1852
- 110 Morse MA, Niedzwiecki D, Marshall JL. et al. A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer. Annals of surgery 2013; 258: 879-886
- 111 Schuler PJ, Harasymczuk M, Visus C. et al. Phase I dendritic cell p53 peptide vaccine for head and neck cancer. Clinical cancer research: an official journal of the American Association for Cancer Research 2014; 20: 2433-2444
- 112 Mould RC, AuYeung AWK, van Vloten JP et al. Enhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections. Scientific Reports 2017; 7:
- 113 Mehrotra S, Britten CD, Chin S. et al. Vaccination with poly(IC:LC) and peptide-pulsed autologous dendritic cells in patients with pancreatic cancer. Journal of hematology & oncology 2017; 10: 82
- 114 Krishnadas DK, Wang Y, Sundaram K. et al. Expansion of cancer germline antigen-specific cytotoxic T lymphocytes for immunotherapy. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine 2017; 39: 1010428317701309
- 115 Dudley ME, Rosenberg SA. Adoptive-cell-transfer therapy for the treatment of patients with cancer. Nature reviews Cancer 2003; 3: 666-675
- 116 Maude SL, Frey N, Shaw PA. et al. Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia. N Engl J Med 2014; 371: 1507-1517
- 117 Dudley ME, Gross CA, Langhan MM. et al. CD8+ enriched "young" tumor infiltrating lymphocytes can mediate regression of metastatic melanoma. Clin Cancer Res 2010; 16: 6122-6131
- 118 Neal LR, Bailey SR, Wyatt MM. et al. The Basics of Artificial Antigen Presenting Cells in T Cell-Based Cancer Immunotherapies. Journal of immunology research and therapy 2017; 2: 68-79
- 119 O'Sullivan D, Pearce EL. Targeting T cell metabolism for therapy. Trends in immunology 2015; 36: 71-80
- 120 Dudley ME, Rosenberg SA. Adoptive Cell Transfer Therapy. Semin Oncol 2007; 34: 524-531
- 121 Sadelain M, Brentjens R, Riviere I. The basic principles of chimeric antigen receptor design. Cancer Discov 2013; 3: 388-398
- 122 Kochenderfer JN, Somerville RPT, Lu T. et al. Long-Duration Complete Remissions of Diffuse Large B Cell Lymphoma after Anti-CD19 Chimeric Antigen Receptor T Cell Therapy. Molecular therapy: the journal of the American Society of Gene Therapy 2017; DOI: 10.1016/j.ymthe.2017.07.004.
- 123 Morgan RA, Yang JC, Kitano M. et al. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Molecular therapy: the journal of the American Society of Gene Therapy 2010; 18: 843-851
- 124 Feng K, Guo Y, Dai H. et al. Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer. Science China Life sciences 2016; 59: 468-479
- 125 Katz SC, Burga RA, McCormack E. et al. Phase I Hepatic Immunotherapy for Metastases Study of Intra-Arterial Chimeric Antigen Receptor-Modified T-cell Therapy for CEA+ Liver Metastases. Clin Cancer Res 2015; 21: 3149-3159
- 126 Beatty GL, Haas AR, Maus MV. et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer immunology research 2014; 2: 112-120
- 127 Davis ID, Skrumsager BK, Cebon J. et al. An open-label, two-arm, phase I trial of recombinant human interleukin-21 in patients with metastatic melanoma. Clin Cancer Res 2007; 13: 3630-3636
- 128 Punch C, Schofield C, Harris P. Rituximab-Associated Inflammatory Progressive Multifocal Leukoencephalopathy. Case reports in infectious diseases 2016; 2016: 8915047
- 129 Hasheminasab SM, Tzvetkov MV, Schumann C. et al. High-throughput screening identified inherited genetic variations in the EGFR pathway contributing to skin toxicity of EGFR inhibitors. Pharmacogenomics 2015; 16: 1605-1619
- 130 Jain D, Ahmad T, Cairo M. et al. Cardiotoxicity of cancer chemotherapy: identification, prevention and treatment. Annals of translational medicine 2017; 5: 348
- 131 Morris KA, Golding JF, Blesing C. et al. Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort. Journal of neuro-oncology 2017; 131: 117-124
- 132 Kunert A, Obenaus M, Lamers CH. et al. T cell receptors for clinical therapy: in vitro assessment of toxicity risk. Clin Cancer Res 2017; DOI: 10.1158/1078-0432.ccr-17-1012.
- 133 Dogan V, Rieckmann T, Munscher A. et al. Current studies of immunotherapy in head and neck cancer. Clinical otolaryngology: official journal of ENT-UK; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery 2017; DOI: 10.1111/coa.12895.
- 134 Curti BD, Kovacsovics-Bankowski M, Morris N. et al. OX40 is a potent immune-stimulating target in late-stage cancer patients. Cancer Res 2013; 73: 7189-7198
- 135 Takada K, Okamoto T, Toyokawa G. et al. The expression of PD-L1 protein as a prognostic factor in lung squamous cell carcinoma. Lung cancer (Amsterdam, Netherlands) 2017; 104: 7-15
- 136 Daud AI, Wolchok JD, Robert C. et al. Programmed Death-Ligand 1 Expression and Response to the Anti-Programmed Death 1 Antibody Pembrolizumab in Melanoma. J Clin Oncol 2016; 34: 4102-4109
- 137 Kansy BA, Concha-Benavente F, Srivastava RM. et al. PD-1 status in CD8+ T cells associates with survival and anti-PD-1 therapeutic outcomes in head and neck cancer. Cancer Res 2017; DOI: 10.1158/0008-5472.can-16-3167.
- 138 Adams DL, Adams DK, He J. et al. Sequential Tracking of PD-L1 Expression and RAD50 Induction in Circulating Tumor and Stromal Cells of Lung Cancer Patients Undergoing Radiotherapy. Clin Cancer Res 2017; DOI: 10.1158/1078-0432.ccr-17-0802.
- 139 Shi X, Zhang X, Li J. et al. PD-1/PD-L1 blockade enhances the efficacy of SA-GM-CSF surface-modified tumor vaccine in prostate cancer. Cancer Lett 2017; 406: 27-35
- 140 Moesta AK, Cooke K, Piasecki J. et al. Local Delivery of OncoVEXmGM-CSF Generates Systemic Anti-Tumor Immune Responses Enhanced by Cytotoxic T-Lymphocyte-Associated Protein Blockade. Clin Cancer Res 2017; DOI: 10.1158/1078-0432.ccr-17-0681.
- 141 Hodi FS, Lee S, McDermott DF. et al. Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. Jama 2014; 312: 1744-1753