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Review article: Biomedical intelligence

Vol. 145 No. 0506 (2015)

Cancer immunology – development of novel anti-cancer therapies

  • Sacha I Rothschild
  • Daniela S Thommen
  • Wolfgang Moersig
  • Philipp Müller
  • Alfred Zippelius
DOI
https://doi.org/10.4414/smw.2015.14066
Cite this as:
Swiss Med Wkly. 2015;145:w14066
Published
25.01.2015

Summary

The vast majority of tumours are characterised by high frequencies of genetic and epigenetic alterations resulting in tumour-specific antigens, which may, in principle, be recognised by cytotoxic T cells. Though early clinical immunotherapy trials have yielded mixed results with ambiguous clinical benefit, cancer immunotherapy is now attracting increasing attention as a viable therapeutic option, mainly in melanoma and lung cancer, but increasingly also in other malignancies. In particular, recent therapeutic efforts targeting inhibitory receptors on T cells to overcome tumour-induced immune dysfunction have the potential to reshape current treatment standards in oncology. The clinical development has been pioneered by the antibody ipilimumab, which blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and has demonstrated survival benefit in two randomised landmark trials in melanoma. Capitalising on this success, the research on the clinical implication of T cell checkpoint inhibition has been boosted. Early clinical trials have demonstrated meaningful response rates, sustained clinical benefits with encouraging survival rates and good tolerability of next-generation checkpoint inhibitors, including programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors, across multiple cancer types. Attractive perspectives include the concurrent blockade of immunological (non-redundant) checkpoints, which has recently been demonstrated using combinations of immune checkpoint modulators themselves or with other therapies, such as chemotherapy, targeted therapy or radiotherapy. This article summarises the mechanism of action and subsequent clinical studies of immune checkpoint antibodies in oncology with a particular focus on melanoma and lung cancer.

References

  1. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med. [Internet]. 2004;10:909–915. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15340416.
  2. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science (80–. ). [Internet]. 2011;331:1565–1570. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21436444.
  3. Mittal D, Gubin MM, Schreiber RD, Smyth MJ. New insights into cancer immunoediting and its three component phases – elimination, equilibrium and escape. Curr Opin Immunol. [Internet]. 2014 [cited 2014 Jun 3];27:16–25. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24531241.
  4. Gajewski TF, Woo S-R, Zha Y, Spaapen R, Zheng Y, Corrales L, et al. Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment. Curr Opin Immunol. [Internet]. 2013 [cited 2014 May 29];25:268–276. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23579075.
  5. Sharma P, Wagner K, Wolchok JD, Allison JP. Novel cancer immunotherapy agents with survival benefit: recent successes and next steps. Nat Rev Cancer [Internet]. 2011 [cited 2014 Jun 25];11:805–812. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3426440&tool=pmcentrez&rendertype=abstract.
  6. Chambers CA, Allison JP. Costimulatory regulation of T cell function. Curr Opin Cell Biol. [Internet]. 1999 Apr [cited 2014 Jun 28];11:203–210. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10209159.
  7. Walunas TL, Lenschow DJ, Bakker CY, Linsley PS, Freeman GJ, Green JM, et al. CTLA-4 can function as a negative regulator of T cell activation. Immunity [Internet]. 1994 [cited 2014 May 27];1:405–413. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7882171.
  8. Simpson TR, Li F, Montalvo-Ortiz W, Sepulveda MA, Bergerhoff K, Arce F, et al. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med. [Internet]. 2013 [cited 2014 May 27];210:1695–1710. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3754863&tool=pmcentrez&rendertype=abstract.
  9. Callahan MK, Wolchok JD. At the bedside: CTLA-4– and PD-1–blocking antibodies in cancer immunotherapy. J Leukoc Biol. [Internet]. 2013 [cited 2014 Jun 17];94:41–53. Available from: http://www.jleukbio.org/search?submit=yes&pubdate_year=&volume=&firstpage=&author1=.
  10. Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol [Internet]. 1999 [cited 2014 Jun 6];17:2105–2116. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10561265.
  11. Rosenberg SA, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA [Internet]. [cited 2014 Jun 5];271:907–913. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8120958.
  12. Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. [Internet]. 2011 [cited 2014 Jun 11];364:2119–2127. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3517182&tool=pmcentrez&rendertype=abstract.
  13. Gure AO, Chua R, Williamson B, Gonen M, Ferrera CA, Gnjatic S, et al. K. Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer. Clin Cancer Res. [Internet]. 2005 [cited 2014 Jun 8];11:8055–8062. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16299236.
  14. Ulloa-Montoya F, Louahed J, Dizier B, Gruselle O, Spiessens B, Lehmann FF, et al. Predictive gene signature in MAGE-A3 antigen-specific cancer immunotherapy. J Clin Oncol. [Internet]. 2013 [cited 2014 May 29];31:2388–2395. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23715562.
  15. Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, Ha TT, 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. [Internet]. 2013 [cited 2014 May 27];5:200ra116. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23986400.
  16. Andtbacka RHI, Collichio FA, Amatruda T, Senzer NN, Chesney J, Delman KA, et al. OPTiM: A randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma. J Clin Oncol. 2013;31(suppl; abstr LBA9008)..
  17. Robert C, Thomas L, Bondarenko I, O’Day S, M DJ, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med [Internet]. 2011;364:2517–2526. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21639810.
  18. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med [Internet]. 2010;363:711–723. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20525992.
  19. Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in metastatic or locally advanced, unresectable melanoma. Eur Cancer Congr. 2013. p. abstract 24..
  20. Robert C, Schadendorf D, Messina M, Hodi FS, O’Day S. Efficacy and safety of retreatment with ipilimumab in patients with pretreated advanced melanoma who progressed after initially achieving disease control. Clin Cancer Res. [Internet]. 2013 [cited 2014 Jun 28];19:2232–2239. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23444228.
  21. Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, 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 [Internet]. 2010;28:3167–3175. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20516446.
  22. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med [Internet]. 2012;366:2443–2454. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22658127.
  23. Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. [Internet]. 2014 Apr [cited 2014 May 23];32:1020–1030. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24590637.
  24. Hamid O, Robert C, Daud A, Hodi FS, Hwu W-J, Kefford R, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. [Internet]. 2013 [cited 2014 May 24];369:134–144. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23724846.
  25. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med [Internet]. 2012;366:2455–2465. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22658128.
  26. Sosman JA, Hamid O, Lawrence D, Sullivan RJ, Ibrahim N, Kluger HM, et al. A study of MPDL3280A (engineered anti-PDL1): activity, safety and characterization of immune response in pre- and on-treatment tumors in metastatic melanoma (mM) pts. Soc Melanoma Res. 2013 Congr. 2013..
  27. Curran MA, Montalvo W, Yagita H, Allison JP. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A. [Internet]. 2010 [cited 2014 May 30];107:4275–4280. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2840093&tool=pmcentrez&rendertype=abstract.
  28. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. [Internet]. 2013 [cited 2014 May 30];369:122–133. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23724867.
  29. Ribas A, Hodi FS, Callahan M, Konto C, Wolchok J. Hepatotoxicity with combination of vemurafenib and ipilimumab. N Engl J Med. [Internet]. 2013 [cited 2014 Jun 7];368:1365–1366. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23550685.
  30. Hodi FS, Lawrence D, Lezcano C, Wu X, Zhou J, Sasada T, et al. Bevacizumab plus Ipilimumab in Patients with Metastatic Melanoma. Cancer Immunol Res. [Internet]. 2014 [cited 2014 May 27]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/24838938.
  31. Holt GE, Podack ER, Raez LE. Immunotherapy as a strategy for the treatment of non-small-cell lung cancer. Therapy [Internet]. 2011 [cited 2014 Jun 28];8:43–54. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3042692&tool=pmcentrez&rendertype=abstract.
  32. Sato Y, Mukai K, Watanabe S, Gotoh M, Matsuno Y, Furuya S, et al. Lymphocyte subsets in pulmonary venous and arterial blood of lung cancer patients. Jpn. J Clin Oncol. [Internet]. 1989 [cited 2014 Jun 28];19:229–236. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2478739.
  33. Wesselius LJ, Wheaton DL, Manahan-Wahl LJ, Sherard SL, Taylor SA, Abdou NA. Lymphocyte subsets in lung cancer. Chest [Internet]. 1987 [cited 2014 Jun 28];91:725–729. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3032522.
  34. Woo EY, Yeh H, Chu CS, Schlienger K, Carroll RG, Riley JL, et al. Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J Immunol. [Internet]. 2002 [cited 2014 Jun 28];168:4272–4276. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11970966.
  35. Al-Shibli KI, Donnem T, Al-Saad S, Persson M, Bremnes RM, Busund L-T. Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin Cancer Res. [Internet]. 2008 [cited 2014 Jun 6];14:5220–5227. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18698040.
  36. Dieu-Nosjean M-C, Antoine M, Danel C, Heudes D, Wislez M, Poulot V, et al. Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. J Clin Oncol. [Internet]. 2008 [cited 2014 Jun 11];26:4410–4417. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18802153.
  37. Hiraoka K, Miyamoto M, Cho Y, Suzuoki M, Oshikiri T, Nakakubo Y, et al. Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma. Br J Cancer [Internet]. 2006 [cited 2014 Jun 17];94:275–280. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2361103&tool=pmcentrez&rendertype=abstract.
  38. Zhuang X, Xia X, Wang C, Gao F, Shan N, Zhang L, Zhang L. A high number of CD8+ T cells infiltrated in NSCLC tissues is associated with a favorable prognosis. Appl. Immunohistochem. Mol. Morphol. [Internet]. 2010 [cited 2014 Jun 28];18:24–28. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19713832.
  39. Takanami I, Takeuchi K, Giga M. The prognostic value of natural killer cell infiltration in resected pulmonary adenocarcinoma. J Thorac Cardiovasc Surg. [Internet]. 2001 [cited 2014 Jun 28];121:1058–1063. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11385371.
  40. Villegas FR, Coca S, Villarrubia VG, Jiménez R, Chillón MJ, Jareño J, et al. Prognostic significance of tumor infiltrating natural killer cells subset CD57 in patients with squamous cell lung cancer. Lung Cancer [Internet]. 2002 [cited 2014 Jun 28];35:23–28. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11750709.
  41. Nemunaitis J, Dillman RO, Schwarzenberger PO, Senzer N, Cunningham C, Cutler J, et al. Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer. J Clin Oncol. [Internet]. 2006 [cited 2014 Jun 28];24:4721–4730. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16966690.
  42. Giaccone G, Bazhenova L, Nemunaitis J, Juhasz E, Ramlau R, van den Heuvel MM, et al. A phase III study of belagenpumatucel-L therapeutic tumor cell vaccine for non-small cell lung cancer (NSCLC). Eur Cancer Congr. 2013. 2013. p. LBA2..
  43. Vansteenkiste J, Zielinski M, Linder A, Dahabreh J, Gonzalez EE, Malinowski W, et al. Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase II randomized study results. J Clin Oncol. [Internet]. 2013 Jul [cited 2014 Jun 3];31:2396–2403. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23715567.
  44. Vansteenkiste JF, Zielinski M, Dahabreh IJ, Linder A, Lehmann F, Gruselle O, et al. Association of gene expression signature and clinical efficacy of MAGE-A3 antigen-specific cancer immunotherapeutic (ASCI) as adjuvant therapy in resected stage IB/II non-small cell lung cancer (NSCLC). J Clin Oncol Off J Am Soc Clin Oncol. 2008;26:abstract 7501..
  45. Sangha R, Butts C. L-BLP25: a peptide vaccine strategy in non small cell lung cancer. Clin Cancer Res. [Internet]. 2007 [cited 2014 May 29];13:s4652–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17671159.
  46. Gendler SJ, Lancaster CA, Taylor-Papadimitriou J, Duhig T, Peat N, Burchell J, et al. Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin. J Biol Chem. [Internet]. 1990 [cited 2014 Jun 28];265:15286–15293. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1697589.
  47. Rochlitz C, Figlin R, Squiban P, Salzberg M, Pless M, Herrmann R, et al. Phase I immunotherapy with a modified vaccinia virus (MVA) expressing human MUC1 as antigen-specific immunotherapy in patients with MUC1–positive advanced cancer. J Gene Med. [Internet]. 2003 [cited 2014 Jun 15];5:690–699. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12898638.
  48. Butts C, Murray N, Maksymiuk A, Goss G, Marshall E, Soulières D, et al. Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer. J Clin Oncol. [Internet]. 2005 [cited 2014 Jun 28];23:6674–6681. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16170175.
  49. Butts CA, Socinski MA, Mitchell P, Thatcher N, Havel L, Krzakowski MJ, et al. START: A phase III study of L-BLP25 (Tecemotide) cancer immunotherapy for unresectable stage III non-small cell lung cancer. J Clin Oncol. 2013;31:abstr 7500..
  50. Quoix E, Ramlau R, Westeel V, Papai Z, Madroszyk A, Riviere A, et al. Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial. Lancet Oncol. [Internet]. 2011 Nov [cited 2014 Jun 10];12:1125–1133. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22019520.
  51. Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol [Internet]. 2012 Jun [cited 2014 Jun 28];30:2046–2054. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22547592.
  52. Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol [Internet]. 2013 [cited 2014 Jun 28];24:75–83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22858559.
  53. Brahmer JR, Horn L, Antonia SJ, Spigel D, Gandhi L, Sequist L V, et al. NIVOLUMAB (ANTI-PD-1; BMS-936558; ONO- 4538) IN PATIENTS WITH NON-SMALL CELL LUNG CANCER (NSCLC): OVERALL SURVIVAL AND LONG-TERM SAFETY IN A PHASE 1 TRIAL. J Thorac Oncol. 2013;8:abstract MO18.03..
  54. Rizvi, Naiyer A, Garon EB, Patnaik A, Gandhi L, Leighl NB, et al. Safety and clinical activity of MK-3475 as initial therapy in patients with advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2014;32:abstr 8007..
  55. Horn L, Herbst RS, Spigel D, Gettinger SN, Gordon MS, Hollebecque A, et al. N ANALYSIS OF THE RELATIONSHIP OF CLINICAL ACTIVITY TO BASELINE EGFR STATUS, PD- L1 EXPRESSION AND PRIOR TREATMENT HISTORY IN PATIENTS WITH NON-SMALL CELL LUNG CANCER (NS- CLC) FOLLOWING PD-L1 BLOCKADE WITH MPDL3280A (ANTI-PDL1. J Thorac Oncol. 2013;8:abstract MO18.01..
  56. Lutzky J, Antonia SJ, Blake-Haskins A, Li X, Robbins PB, Shalabi AM, et al. A phase 1 study of MEDI4736, an anti–PD-L1 antibody, in patients with advanced solid tumors. J Clin Oncol. 2014;32:abstr 3001.
  57. Goldman B, DeFrancesco L. The cancer vaccine roller coaster. Nat Biotechnol. [Internet]. 2009 [cited 2014 Jun 28];27:129–139. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19204689.
  58. Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, et al. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol [Internet]. 2006;24:3089–3094. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16809734.
  59. Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, et al. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer [Internet]. 2009;115:3670–3679. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19536890.
  60. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med [Internet]. 2010;363:411–422. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20818862.
  61. Pardoll D, Drake C. Immunotherapy earns its spot in the ranks of cancer therapy. J Exp Med [Internet]. 2012;209:201–209. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22330682.
  62. Weber JS, Kähler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. [Internet]. 2012 Jul [cited 2014 Jun 4];30:2691–2697. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22614989.
  63. Lebbé C, O’Day S, Chiarion Sileni V, Al. E. Analysis of the onset and resolution of immune-related adverse events during treatment with ipilimumab in patients with metastatic melanoma. Proc. from Perspect. Melanoma XII; Oct. 2–4, 2008. 2008. p. Abstract O–015..
  64. Rubin KM. Managing immune-related adverse events to ipilimumab: a nurse’s guide. Clin J Oncol Nurs. [Internet]. 2012 [cited 2014 Jun 28];16:E69–75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22459539.
  65. Di Giacomo AM, Biagioli M, Maio M. The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical indications. Semin Oncol. [Internet]. 2010 [cited 2014 Jun 28];37:499–507. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21074065.
  66. Attia P, Phan GQ, Maker A V, Robinson MR, Quezado MM, Yang JC, et al. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J. Clin. Oncol. [Internet]. 2005 [cited 2014 Jun 12];23:6043–6053. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1473965&tool=pmcentrez&rendertype=abstract.
  67. Agarwala SS, Ribas A. Current experience with CTLA4–blocking monoclonal antibodies for the treatment of solid tumors. J Immunother. [Internet]. [cited 2014 Jun 28];33:557–569. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20551840.
  68. Patnaik A, Kang SP, Tolcher AW, Rasco DW, Papadopoulos KP, Beeram M, et al. Phase I study of MK-3475 (anti-PD-1 monoclonal antibody) in patients with advanced solid tumors. J Clin Oncol. 2012;30:abstr 2512..
  69. Davies M. New modalities of cancer treatment for NSCLC: focus on immunotherapy. Cancer Manag Res. [Internet]. 2014 [cited 2014 Jun 28];6:63–75. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3917949&tool=pmcentrez&rendertype=abstract.

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