title: Targeted therapy in renal cell carcinoma: moving from molecular agents to specific immunotherapy.
abstract: Non-specific immunotherapy has been for a long time a standard treatment option for patients with metastatic renal cell carcinoma but was redeemed by specific targeted molecular therapies, namely the VEGF and mTOR inhibitors. After moving treatment for mRCC to specific molecular agents with a well-defined mode of action, immunotherapy still needs this further development to increase its accuracy. Nowadays, an evolution from a rather non-specific cytokine treatment to sophisticated targeted approaches in specific immunotherapy led to a re-launch of immunotherapy in clinical studies. Recent steps in the development of immunotherapy strategies are discussed in this review with a special focus on peptide vaccination which aims at a tumor targeting by specific T lymphocytes. In addition, different combinatory strategies with immunomodulating agents like cyclophosphamide or sunitinib are outlined, and the effects of immune checkpoint modulators as anti-CTLA-4 or PD-1 antibodies are discussed.
authors: Department of Urology, Eberhard Karls University Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany, bedke@live.com.
authors: Jens
authors: J
authors: Bedke
authors: Cécile
authors: C
authors: Gouttefangeas
authors: Harpreet
authors: H
authors: Singh-Jasuja
authors: Stefan
authors: S
authors: Stevanović
authors: Carl-Ludwig
authors: CL
authors: Behnes
authors: Arnulf
authors: A
authors: Stenzl
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D019496:Cancer Vaccines / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods / Q000639:trends*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D042461:Vascular Endothelial Growth Factor A; D058570:TOR Serine-Threonine Kinases
references: Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4163-70
references: 16857787
references: Annu Rev Immunol. 1996;14:483-510
references: 8717522
references: J Clin Oncol. 2010 May 1;28(13):2144-50
references: 20368553
references: Clin Cancer Res. 2008 Oct 15;14(20):6674-82
references: 18927310
references: Eur Urol. 2010 Sep;58(3):398-406
references: 20633979
references: J Cancer. 2011;2:333-8
references: 21716852
references: Clin Cancer Res. 2007 Apr 1;13(7):2100-8
references: 17404092
references: Lancet. 2004 Feb 21;363(9409):594-9
references: 14987883
references: J Immunol. 1999 Aug 1;163(3):1690-5
references: 10415076
references: J Clin Oncol. 2010 May 1;28(13):2137-43
references: 20368558
references: J Clin Oncol. 2003 Aug 15;21(16):3127-32
references: 12915604
references: Blood. 2006 Mar 15;107(6):2409-14
references: 16304057
references: Nat Rev Cancer. 2008 Aug;8(8):618-31
references: 18633355
references: J Clin Invest. 2007 May;117(5):1167-74
references: 17476346
references: Cancer J. 2011 Sep-Oct;17(5):325-30
references: 21952282
references: Am J Clin Oncol. 1997 Aug;20(4):416-8
references: 9256902
references: Clin Cancer Res. 2008 Dec 15;14(24):8270-8
references: 19088044
references: Hum Gene Ther. 2005 Jul;16(7):799-810
references: 16000062
references: Nat Med. 2012 Aug;18(8):1254-61
references: 22842478
references: Clin Cancer Res. 2005 May 15;11(10):3714-21
references: 15897568
references: Prostate. 2009 Jun 15;69(9):917-27
references: 19267352
references: N Engl J Med. 2010 Aug 19;363(8):711-23
references: 20525992
references: Clin Cancer Res. 2009 Oct 1;15(19):6225-31
references: 19755389
references: Cancer Immunol Immunother. 2012 Jul;61(7):967-78
references: 22714399
references: Nat Rev Clin Oncol. 2009 Aug;6(8):478-87
references: 19546865
references: Clin Cancer Res. 2010 Nov 15;16(22):5539-47
references: 20881001
references: J Immunol. 1993 Oct 15;151(8):4209-20
references: 8409397
references: Annu Rev Immunol. 1993;11:213-44
references: 8476560
references: Clin Cancer Res. 2006 Mar 15;12(6):1768-75
references: 16551861
references: N Engl J Med. 2012 Jun 28;366(26):2443-54
references: 22658127
references: Cancer Res. 2009 Nov 1;69(21):8412-9
references: 19843860
references: Ann Oncol. 2012 Sep;23 Suppl 8:viii35-40
references: 22918926
references: Expert Rev Anticancer Ther. 2012 Jun;12(6):777-85
references: 22716494
references: Cancer Immunol Immunother. 2008 Mar;57(3):289-302
references: 17721783
references: J Immunol. 2000 Jun 1;164(11):5583-9
references: 10820232
references: Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11895-9
references: 20547850
references: Clin Cancer Res. 2009 Mar 15;15(6):2148-57
references: 19276286
references: Tissue Antigens. 2010 Feb;75(2):110-8
references: 19912575
references: Cancer Res. 2006 Jun 1;66(11):5910-8
references: 16740731
references: Expert Rev Vaccines. 2011 Jun;10(6):837-52
references: 21692704
references: Cancer. 2003 Jan 1;97(1):186-200
references: 12491520
references: J Clin Oncol. 2010 Nov 1;28(31):4722-9
references: 20921459
references: Lancet. 2008 Jul 12;372(9633):145-54
references: 18602688
references: Science. 1991 Dec 13;254(5038):1643-7
references: 1840703
references: N Engl J Med. 2007 Jan 11;356(2):115-24
references: 17215529
references: Ann Oncol. 2012 Oct;23 Suppl 7:vii65-71
references: 22997456
references: Sci Transl Med. 2011 Nov 9;3(108):108ps44
references: 22072636
references: J Immunother. 2007 Nov-Dec;30(8):825-30
references: 18049334
references: Nature. 2008 Jul 24;454(7203):436-44
references: 18650914
references: Cancer Res. 2002 Oct 15;62(20):5818-27
references: 12384544
references: Blood. 2008 Jun 15;111(12):5610-20
references: 18310500