Immunotherapy of Urothelial Carcinoma of the Bladder – from BCG Vaccines to Targeted Therapy

Česká verzia

Authors: M. Matoušková
Authors place of work: Urocentrum Praha
Published in the journal: Klin Onkol 2015; 28(Supplementum 4): 95-102
Category: Specials
doi: https://doi.org/10.14735/amko20154S95

Summary

Bladder cancer has high prevalence in men and women. Bladder cancer usually originates from urothelium. More than 75% of cases are classified as non‑muscle‑ invasive bladder cancer. Urothelial bladder carcinoma is usually managed by transurethral resection of the bladder tumor. Role of transurethral resection of the bladder tumor is also essential in bladder cancer staging. Local prophylaxis is used in non‑muscle‑ invasive bladder cancer to reduce risk of recurrence. While local chemoprophylaxis is sufficient in low and middle risk patients, intravesical instillation of Mycobacterium bovis bacillus Calmette‑Guerin (BCG) is preferred in high risk bladder cancer. Chemotherapy alone or in combination with locoregional treatment is used in advanced bladder cancer. New immunotherapy modalities have proven their efficacy in several clinical studies in advanced bladder cancer.

Key words:
urothelial bladder cancer – immunotherapy – BCG vaccine – checkpoint inhibitor

The author declares she has no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
3. 9. 2015

Accepted:
23. 10. 2015

Zdroje

1. Ferlay J, Bray F, Forman D et al. GLOBOCAN 2008 v1.2, Cancer incidence and mortality worldwide: IARC cancer base No. 10 [monograph on the Internet]. Lyon: International Agency for Research on Cancer 2010. Available from: www.iarc.fr/ en/ publications/ eresources/ cancerbases/ index.php.

2. Globocan 2012: estimated cancer incindence, mortality and prevalence worldwide in 2012 [online]. Lyon: International Agency for Research on Cancer 2015. Available from: www.globocan.iarc.fr.

3. Nádory močového měchýře – Epidemiologie a populační data ČR [online]. Masarykova univerzita, Brno, 2015. [citováno 30. září 2015]. Dostupné z: www.uroweb.cz/ index.php?pg=dg‑ nadory‑ mocoveho‑ mechyre‑ epidemiologie‑ ceska‑ republika‑ vyvoj‑ incidence‑ mortalitahttp:/ / www.uroweb.cz.

4. Babjuk M, Böhle A, Burger M el al. Guidelines on non‑muscle‑ invasive bladder cancer (Ta, T1 and CIS), limited update March 2015 [monograph on the Internet]. European Association of Urology 2015. Available from: http:/ / uroweb.org/ wp‑ content/ uploads/ EAU‑ Guidelines‑ Non‑ muscle‑ invasive‑ Bladder‑ Cancer‑ 2015-v1.pdf.

5. Zhoubný novotvar močového měchýře (C67) [online]. Modrá kniha. [citováno 30. září 2015]. Dostupné z: www.linkos.cz/ informace‑ pro‑praxi/ modra‑ kniha/ 22- zhoubny‑ novotvar‑ mocoveho‑ mechyre‑c67/ .

6. Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette Guerin in the treatment of superficial bladder tumors. J Urol 1976; 116(2): 180– 183.

7. Lamm DL, Blumenstein BA, Crawford ED et al. A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette‑ Guerin for transitional‑ cell carcinoma of the bladder. N Engl J Med 1991; 325(17): 1205– 1209.

8. Malmström PU, Wijkström H, Lundholm C et al. 5‑year followup of a randomized prospective study comparing mitomycin C and bacillus Calmette‑ Guerin in patients with superficial bladder carcinoma. J Urol 1999; 161(4): 1124– 1127.

9. van der Meijden AP, Sylvester RJ, Oosterlinck W et al. Maintenance bacillus Calmette‑ Guerin for Ta T1 bladder tumors is not associated with increased toxicity: results from a European organisation for research and treatment of cancer genito‑ urinary group phase III trial. Eur Urol 2003; 44(4): 429– 434.

10. Morales A, Ottenhof P, Emerson L. Treatment of residual, non‑infiltrating bladder cancer with bacillus Calmette‑ Guerin. J Urol 1981; 125(5): 649– 651.

11. Hall MC, Chang SS, Dalbagni G et al. Guideline for the management of nonmuscle invasive bladder cancer (stages Ta, T1, and Tis): 2007 update. J Urol 2007; 178(6): 2314– 2330.

12. Kavoussi R, Brown JE, Ritchey JK et al. Fibronectin‑mediated Calmette‑ Guerin bacillus attachment to murine bladder mucosa. Requirement for the expression of an antitumor response. J Clin Invest 1990; 85(1): 62– 67.

13. Zuiverloon TC, Nieuweboer AJ, Vékony H el al. Markers predicting response to bacillus Calmette‑ Guérin immunotherapy in high‑risk bladder cancer patients: a systematic review. Eur Urol 2012; 61(1): 128– 145. doi: 10.1016/ j.eururo.2011.09.026.

14. Luo Y, Chen X, O‘Donnell MA. Role of Th1 and Th2 cytokines in BCG‑induced IFN‑ γ production: cytokine promotion and simulation of BCG effect. Cytokine 2003; 21(1): 17– 26.

15. Saint F, Patard JJ, Maille P et al. Prognostic value of a T helper 1 urinary cytokine response after intravesical bacillus Calmette‑ Guerin treatment for superficial bladder cancer. J Urol 2002; 167(1): 364– 367.

16. Lamm DL, Blumenstein BA, JCrissman JD et al. Maintenance bacillus Calmette‑ Guerin immunotherapy for recurrent Ta, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group study. J Urol 2000; 163(4): 1124– 1129.

17. Jonasch E, Haluska FG. Interferon in oncological practice: review of interferon biology, clinical applications, and toxicities. Oncologist 2001; 6(1): 34– 55.

18. Kamat AM, Lamm DL. Immunotherapy for bladder cancer. Curr Urol Rep 2001; 2(1): 62– 69.

19. Belardelli F, Ferrantini M, Proietti E et al. Interferon‑alpha in tumor immunity and immunotherapy. Cytokine Growth Factor Rev 2002; 13(2): 119– 134.

20. Droller MJ, Gomolka D. Enhancement of natural cytotoxicity in lymphocytes from animals with carcinogen‑induced bladder cancer. J Urol 1983; 129(3): 625– 629.

21. Parronchi P, De Carli M, Manetti R et al. IL‑4 and IFN (α and γ) exert opposite regulatory effects on the development of cytolytic potential by Th1 or Th2 human T cell clones. J Immunol 1992; 149(9): 2977– 2983.

22. Slaton JW, Perrotte P, Inoue K el al. Interferon‑ α‑ mediated down‑ regulation of angiogenesis‑related genes and therapy of bladder cancer are dependent on optimization of biological dose and schedule. Clin Cancer Res 1999; 5(10): 2726– 2734.

23. Giannopoulos A, Adamakis I, Evangelou K et al. Interferon‑ a2b reduces neo‑ microvascular density in the ‚normal‘ urothelium adjacent to the tumor after transurethral resection of superficial bladder carcinoma. Onkologie 2003; 26(2): 147– 152.

24. Glashan RW. A randomized controlled study of intravesical α‑ 2b‑ interferon in carcinoma in situ of the bladder. J Urol 1990; 144(3): 658– 661.

25. Hudson MA, Ratliff TL. Failure of intravesical interferon‑alfa‑2b for the treatment of patients with superficial bladder cancer previously failing intravesical BCG therapy. Urol Oncol 1995; 1(3): 115– 118.

26. Portillo J, Martin B, Hernandez R et al. Results at 43 months‘ follow‑up of a double‑blind, randomized, prospective clinical trial using intravesical interferon alpha‑ 2b in the prophylaxis of stage pT1 transitional cell carcinoma of the bladder. Urology 1997; 49(2): 187– 190.

27. Gan YH, Zhang Y, Khoo HE et al. Antitumour immunity of bacillus Calmette‑ Guerin and interferon alpha in urine bladder cancer. Eur J Cancer 1999; 35(7): 1123– 1129.

28. Luo Y, Chen X, Downs TM el al. IFN‑ α 2B enhances Th1 cytokine responses in bladder cancer patients receiving Mycobacterium bovis bacillus Calmette‑ Guerin immunotherapy. J Immunol 1999; 162(4): 2399– 2405.

29. Lam JS, Benson MC, O‘Donnell MA et al. Bacillus Calmete‑ Guérin plus interferon‑ α2B intravesical therapy maintains an extended treatment plan for superficial bladder cancer with minimal toxicity. Urol Oncol 2003; 21(5): 354– 360.

30. Nagabhushan TL, Maneval DC, Benedict WF et al. Enhancement of intravesical delivery with Syn3 potentiates interferon‑ α2b gene therapy for superficial bladder cancer. Cytokine Growth Factor Rev 2007; 18(5– 6): 389– 394.

31. Gillis S, Smith KA. Long term culture of tumour specific cytotoxic T cells. Nature 1977; 268(5616): 154– 156.

32. Di Sabato G, Chen DM, Erickson JW. Production by murine spleen cells of an activity stimulating the PHA responsiveness of thymus lymphocytes. Cell Immunol 1975; 17(2): 495– 504.

33. Lotze MT, Grimm EA, Mazumder A. Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T‑ cell growth factor. Cancer Res 1981; 41(11): 4420– 4425.

34. Henney CS, Kuribayashi K, Kern DE et al. Interleukin‑2 augments natural killer cell activity. Nature 1981; 291(5813): 335– 338.

35. Waldmann TA, Goldman CK, Robb RJ. Expression of interleukin 2 receptors on activated human B cells. J Exp Med 1984; 160(5): 1450– 1466.

36. Mosmann TR, Cherwinski H, Bond MW et al. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986; 136(7): 2348– 2357.

37. De Reijke TM, De Boer EC, Kurth KH et al. Urinary interleukin‑2 monitoring during prolonged bacillus Calmette‑ Guerin treatment: can it predict the optimal number of instillations? J Urol 1999; 161(1): 67– 71.

38. De Boer EC, De Jong WH, Steerenberg PA et al. Leukocytes and cytokines in the urine of superficial bladder cancer patients after intravesical immunotherapy with bacillus Calmette‑ Guerine. In Vivo 1991; 5(6): 671– 677.

39. Magno C, Melloni D, Galì A et al. The anti‑tumor activity of bacillus Calmette‑ Guerin in bladder cancer is associated with an increase in the circulating level of interleukin‑2. Immunol Lett 2002; 81(3): 235– 238.

40. Merguerian PA, Donahue L, Cockett AT. Intraluminal interleukin 2 and bacillus Calmette‑ Guerin for treatment of bladder cancer: a preliminary report. J Urol 1987; 137(2): 216– 219.

41. Huland E, Huland H. Local continuous high dose interleukin 2: a new therapeutic model for the treatment of advanced bladder carcinoma. Cancer Res 1989; 49(19): 5469– 5474.

42. Cockett AT, Davis RS, Cos LR et al. Bacillus calmette‑ guerin and interleukin‑2 for treatment of superficial bladder cancer. J Urol 1991; 146(3): 766– 769.

43. Gomella LG, McGinnis DE, Lattime EC et al. Treatment of transitional cell carcinoma of the bladder with intravesical interleukin‑2: a pilot study. Cancer Biother 1993; 8(3): 223– 227.

44. Den Otter W, Dobrowolski Z, Bugajski A et al. Intravesical interleukin‑2 in T1 papillary bladder carcinoma: regression of marker lesion in 8 of 10 patients. J Urol 1998; 159(4): 1183– 1186.

45. O‘Donnell MA, Aldovini A, Duda RB et al. Recombinant Mycobacterium bovis BCG secreting functional interleukin‑2 enhances gamma interferon production by splenocytes. Infect Immun 1994; 62(6): 2508– 2514.

46. Young SL, O‘Donnell MA, Buchan GS. IL‑2secreting recombinant bacillus Calmette Guerin can overcome a type 2 immune response and corticosteroid‑induced immunosupression to elicit a type 1 immune response. Int Immunol 2002; 14(7): 793– 800.

47. Zhang X, Shi X, Li J et al. Novel immunotherapy for metastatic bladder cancer using vaccine of human interleukin‑2 surface‑ modified MB 49 cells. Urology 2011; 78(3): 722. doi: 10.1016/ j.urology.2011.04.044.

48. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12(4): 252– 264. doi: 10.1038/ nrc3239.

49. Finn OJ. Immuno‑ oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol 2012, 23 (Suppl 8): viii6– viii9. doi: 10.1093/ annonc/ mds256.

50. Kim JW, Tomita Y, Trepel J et al. Emerging immunotherapies for bladder cancer. Curr Opin Oncol 2015; 27(3): 191– 200. doi: 10.1097/ CCO.0000000000000177.

51. Powels T, Eder JP, Fine GD et al. MPDL3280A (anti‑PD‑ L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014; 515(7528): 558– 562. doi: 10.1038/ nature13904.

52. Tarhini A, Lo E, Minor DR. Releasing the brake on the immune system: ipilimumab in melanoma and other tumors. Cancer Biother Radiopharm 2010; 25(6): 601– 613. doi: 10.1089/ cbr.2010.0865.

53. Plimack ER, Gupta S, Bellmunt J et al. A phase 1b study of pembrolizumab (Pembro; MK‑ 3475) in patients (pts) with advanced urothelial tract cancer. Ann Oncol 2014; 25(5): 1– 41. doi: 10.1093/ annonc/ mdu438.

54. Segal NH, Hamid O, Hwu W et al. A phase I multi‑arm dose‑expansion study of the anti‑programmed cell death‑ligand‑ 1 (PD‑ L1) antibody MEDI4736: preliminary data. Ann Oncol 2014; 25 (Suppl 4): iv361– iv372. doi: 10.1093/ annonc/mdu342.