Pharmacological inhibition of TGFβ as a strategy to augment the antitumor immune response

Current Opinion in Investigational Drugs

Volumn 11, Issue 12, 2010, Pages 1342-1353

  Hanks, Brent A ^a   Morse, Michael A ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Immunosuppression; immunosurveillance; immunotherapy; serine threonine kinase inhibitor; TGF ; vaccine

Indexed keywords

ADENOVIRUS VECTOR; ANTINEOPLASTIC AGENT; FRESOLIMUMAB; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; PEPTIDE VACCINE; PROTEIN SERINE THREONINE KINASE INHIBITOR; SD 208; SM 16; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA ANTIBODY; TRANSFORMING GROWTH FACTOR BETA RECEPTOR; TUMOR CELL VACCINE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER IMMUNOTHERAPY; CANCER INHIBITION; COLON CANCER; GLIOMA; HUMAN; IMMUNE SYSTEM; IMMUNOREGULATION; IN VITRO STUDY; IN VIVO STUDY; KIDNEY CARCINOMA; LYMPHOCYTIC INFILTRATION; MELANOMA; MESOTHELIOMA; NEOPLASM; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; TUMOR IMMUNITY;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; HUMANS; IMMUNOTHERAPY; MOLECULAR WEIGHT; NEOPLASMS; TRANSFORMING GROWTH FACTOR BETA;

EID: 79952766630     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (65)

1. Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA: Transforming growth factor-β regulation of immune responses. Annu Rev Immunol (2006) 24:99-146.
2. Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, Yin M, Allen R, Sidman C, Proetzel G, Calvin D, Annunziata N et al: Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease. Nature (1992) 359(6397):693-699.
3. Gorelik L, Flavell R: Transforming growth factor-β in T cell biology. Nature Rev Immunol (2002) 2(1):46-53. (Pubitemid 37328775)
4. Fainaru O, Shseyov D, Hantisteanu S, Groner Y: Accelerated chemokine receptor 7-mediated dendritic cell migration in Runx3 knockout mice and the spontaneous development of asthma-like disease. Proc Natl Acad Sci USA (2005) 102(30):10598-10603. (Pubitemid 41061600)
5. Strobl H, Knapp W: TGF-β1 regulation of dendritic cells. Microbes Infection (1999) 1(15):1283-1290.
6. Yamazaki S, Inaba K, Tarbell KV, Steinman RM: Dendritic cells expand antigen-specific FoxP3+ CD25+ CD4+ regulatory T cells including suppressors of alloreactivity. Immunol Rev (2006) 212:314-329. (Pubitemid 44116717)
7. Laouar Y, Town T, Jeng D, Tran E, Wan Y, Kuchroo VK, Flavell RA: TGF-β signaling in dendritic cells is a prerequisite for the control of autoimmune encephalomyelitis. Proc Natl Acad Sci USA (2008) 105(31):10865-10870.
8. Hersey P: Impediments to successful immunotherapy. Pharmacol Ther (1999) 81(2):111-119. (Pubitemid 29073559)
9. Teicher BA: Transforming growth factor-β and the immune response to malignant disease. Clin Cancer Res (2007) 13(21):6247-6251. (Pubitemid 350075011)
10. Kirkbride KC, Blobe GC: Inhibiting the TGF-β signalling pathway as a means of cancer immunotherapy. Expert Opin Biol Ther (2003) 3(2):251-261. (Pubitemid 36458757)
11. Gajewski TF, Meng Y, Blank C, Brown I, Kacha A, Kline J, Harlin H: Immune resistance orchestrated by the tumor microenvironment. Immunol Rev (2006) 213:131-145. (Pubitemid 44401498)
12. Torre-Amione G, Beauchamp RD, Koeppen H, Park BH, Schreiber H, Moses HL, Rowley DA: A highly immunogenic tumor transfected with a murine transforming growth factor type β1 cDNA escapes immune surveillance. Proc Natl Acad Sci USA (1990) 87(4):1486-1490.
13. Mathews E, Yang T, Janulis L, Goodwin S, Kundu SD, Karpus WJ, Lee C: Down-regulation of TGF-β1 production restores immunogenicity in prostate cancer cells. Brit J Cancer (2000) 83(4):519-525. (Pubitemid 30487867)
14. Won J, Kim H, Park EJ, Hong Y, Kim SJ, Yun Y: Tumorigenicity of mouse thymoma is suppressed by soluble type II transforming growth factor β receptor therapy. Cancer Res (1999) 59(6):1273-1277. (Pubitemid 29136258)
15. Disis ML, Wallace DR, Gooley TA, Dang Y, Slota M, Lu H, Coveler AL, Childs JS, Higgins DM, Fintak PA, dela Rosa C et al: Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer. J Clin Oncol (2009) 27(28):4685-4692.
16. Gorelik L, Flavell RA: Immune-mediated eradication of tumors through the blockade of transforming growth factor-β signaling in T cells. Nat Med (2001) 7(10):1118-1122. (Pubitemid 33010019)
17. Zhang Q, Yang X, Pins M, Javonovic B, Kuzel T, Kim SJ, Parijs LV, Greenberg NM, Liu V, Guo Y, Lee C: Adoptive transfer of tumor-reactive transforming growth factor-β-insensitive CD8+ T cells: Eradication of autologous mouse prostate cancer. Cancer Res (2005) 65(5):1761-1769. (Pubitemid 40478602)
18. Wang L, Wen W, Yuan J, Helfand B, Li Y, Shi C, Tian F, Zheng J, Wang F, Chen L, Liang L et al: Immunotherapy for human renal cell carcinoma by adoptive transfer of autologous transforming growth factor β-insensitive CD8+ T cells. Clin Cancer Res (2010) 16(1):164-173.
19. Saunier E, Akhurst R: TGF β inhibition for cancer therapy. Curr Cancer Drug Targets (2006) 6(7):565-578.
20. Biswas S, Criswell TL, Wang SE, Arteaga CL: Inhibition of transforming growth factor-β signaling in human cancer: Targeting a tumor suppressor network as a therapeutic strategy. Clin Cancer Res (2006) 12(14 Pt 1):4142-4146.
21. Nagaraj NS, Datta PK: Targeting the transforming growth factor-β signaling pathway in human cancer. Expert Opin Investig Drugs (2010) 19(1):77-91.
22. Bierie B, Moses HL: Tumour microenvironment: TGFβ: The molecular Jekyll and Hyde of cancer. Nature Rev Cancer (2006) 6(7):506-520. (Pubitemid 43980540)
23. Arteaga CL, Hurd SD, Winnier AR, Johnson MD, Fendly BM, Forbes JT: Anti-transforming growth factor (TGF)-β antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity: Implications for a possible role of tumor cell/host TGF-β interactions in human breast cancer progression. J Clin Invest (1993) 92(6):2569-2576. (Pubitemid 24006519)
24. Kobie JJ, Wu RS, Kurt RA, Lou S, Adelman MK, Whitesell LJ, Ramanathapuram LV, Arteaga CL, Akporiaye ET: Transforming growth factor b inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines. Clin Cancer Res (2003) 63(8):1860-1864. (Pubitemid 36460849)
25. Suzuki E, Kapoor V, Cheung HK, Ling LE, DeLong PA, Kaiser LR, Albelda SM: Soluble type II transforming growth factor-β receptor inhibits established murine malignant mesothelioma tumor growth by augmenting host antitumor immunity. Clin Cancer Res (2004) 10(17):5907-5918. (Pubitemid 39180973)
26. Nam JS, Terabe M, Mamura M, Kang MJ, Chae H, Stuelten C, Kohn E, Tang B, Sabzevari H, Anver MR, Lawrence S et al: An anti-TGF-β antibody suppresses metastasis via cooperative effects on multiple cell compartments. Cancer Res (2008) 68(10):3835-3843.
27. Liu VC, Wong LY, Jang T, Shah AH, Park I, Yang X, Zhang Q, Lonning S, Teicher BA, Lee C: Tumor evasion of the immune system by converting CD4+CD25+ T regulatory cells: Role of tumor-derived TGF-β. J Immunol (2007) 178(5):2883-2892.
28. Shimizu J, Yamazaki S, Sakaguchi S: Induction of tumor immunity by removing CD25+CD4+ T cells: A common basis between tumor immunity and autoimmunity. J Immunol (1999) 163(10):5211-5218.
29. Morris J, Shapiro G, Tan A, Lawrence D, Olencki T, Dezube B, Hsu F, Reiss M, Berzofsky J: Phase I/II study of GC1008: A human anti-transforming growth factor-β (TGFβ) monoclonal antibody (mAb) in patients with advanced malignant melanoma (MM) or renal cell carcinoma (RCC). J Clin Oncol (2008) 26(15S):9028.
30. Morris J, Wood L, Terabe M, Shapiro G, Tan A, Lawrence D, Olencki T, Dezube B, Reiss M, Hsu F, Berzofsky J: Anti-TGF-β as a cancer therapeutic in mice and humans: A phase I study of GC1008, a human anti-TGF-β monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma. NCI Translational Science Meeting, Vienna, VA, USA (2009):Abs 416
31. Zhong Z, Carroll KD, Policarpio D, Osborn C, Gregory M, Bassi R, Jimenez X, Prewett M, Liebisch G, Persaud K, Burtrum D et al: Anti-transforming growth factor β receptor II antibody has therapeutic efficacy against primary tumor growth and metastasis through multieffects on cancer, stroma, and immune cells. Clin Cancer Res (2010) 16(4):1191-1205.
32. Bandyopadhyay A, Zhu Y, Cibull M, Bao L, Chen C, Sun L: A soluble transforming growth factor β type III receptor suppresses tumorigenicity and metastasis of human breast cancer MDA-MB-231 cells. Cancer Res (1999) 59(19):5041-5046. (Pubitemid 29472913)
33. Bandyopadhyay A, López-Casillas F, Malik SN, Montiel JL, Mendoza V, Yang J, Sun LZ: Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft. Cancer Res (2002) 62(16):4690-4695.
34. Rowland-Goldsmith MA, Maruyama H, Kusama T, Ralli S, Korc M: Soluble type II transforming growth factor-β (TGF-β) receptor inhibits TGF-β signaling in COLO-357 pancreatic cancer cells in vitro and attenuates tumor formation. Clin Cancer Res (2001) 7(9):2931-2940. (Pubitemid 32911404)
35. Muraoka RS, Dumont N, Ritter CA, Dugger TC, Brantley DM, Chen J, Easterly E, Roebuck LR, Ryan S, Gotwals PJ, Koteliansky V et al: Blockade of TGF-β inhibits mammary tumor cell viability, migration, and metastases. J Clin Invest (2002) 109(12):1551-1559. (Pubitemid 34663517)
36. Verona EV, Tang Y, Millstead TK, Hinck AP, Agyin JK, Sun L-Z: Expression, purification, and characterization of BGERII: A novel pan-TGFβ inhibitor. Protein Eng Design Selection (2008) 21(7):463-473. (Pubitemid 351882136)
37. Yingling JM, Blanchard KL, Sawyer JS: Development of TGF-β signalling inhibitors for cancer therapy. Nature Rev Drug Discov (2004) 3(12):1011-1022. (Pubitemid 39642364)
38. Guckian K, Carter M, Lin E, Choi M, Sun L, Boriack-Sjodin P, Chuaqui C, Lane B, Cheung K, Ling L, Lee W-C: Pyrazolone based TGFβR1 kinase inhibitors. Bioorg Med Chem Lett (2009) 50(1):326-329.
39. Sawyer JS, Anderson BD, Beight DW, Campbell RM, Jones ML, Herron DK, Lampe JW, McCowan JR, McMillen WT, Mort N, Parsons S et al: Synthesis and activity of new aryl-and heteroaryl-substituted pyrazole inhibitors of the transforming growth factor-β type I receptor kinase domain. J Med Chem (2003) 46(19):3953-3956. (Pubitemid 37122441)
40. Inman GJ, Nicolás FJ, Callahan JF, Harling JD, Gaster LM, Reith AD, Laping NJ, Hill CS: SB-431542 is a potent and specific inhibitor of transforming growth factor-β superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol Pharmacol (2002) 62(1):65-74. (Pubitemid 34680517)
41. Ge R, Rajeev V, Ray P, Lattime E, Rittling S, Medicherla S, Protter A, Murphy A, Chakravarty J, Dugar S, Schreiner G et al: Inhibition of growth and metastasis of mouse mammary carcinoma by selective inhibitor of transforming growth factor-β type I receptor kinase in vivo. Clin Cancer Res (2006) 12(14):4315-4330.
42. Uhl M, Aulwurm S, Wischhusen J, Weiler M, Ma JY, Almirez R, Mangadu R, Liu YW, Platten M, Herrlinger U, Murphy A et al: SD-208, a novel transforming growth factor β receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenecity of murine and human glioma cells in vitro and in vivo. Cancer Res (2004) 64(21):7954-7961. (Pubitemid 39446929)
43. Suzuki E, Kim S, Cheung HK, Corbley MJ, Zhang X, Sun L, Shan F, Singh J, Lee WC, Albelda SM, Ling LE: A novel small-molecule inhibitor of transforming growth factor β type I receptor kinase (SM16) inhibits murine mesothelioma tumor growth in vivo and prevents tumor recurrence after surgical resection. Cancer Res (2007) 67(5):2351-2359. (Pubitemid 46424257)
44. Rausch MP, Hahn T, Ramanathapuram L, Bradley-Dunlop D, Mahadevan D, Mercado-Pimentel ME, Runyan RB, Besselsen DG, Zhang X, Cheung HK, Lee WC et al: An orally active small molecule TGF-β receptor I antagonist inhibits the growth of metastatic murine breast cancer. Anticancer Res (2009) 29(6):2099-2109.
45. Pardoll D, Allison J: Cancer immunotherapy: Breaking the barriers to harvest the crop. Nature Med (2004) 10(9):887-892. (Pubitemid 39273721)
46. Kim S, Buchlis G, Fridlender ZG, Sun J, Kapoor V, Cheng G, Haas A, Cheung HK, Zhang X, Corbley M, Kaiser LR et al: Systemic blockade of transforming growth factor-β signaling augments the efficacy of immunogene therapy. Cancer Res (2008) 68(24):10247-10256.
47. Wallace A, Kapoor V, Sun J, Mrass P, Weninger W, Heitjan DF, June C, Kaiser LR, Ling LE, Albelda SM: Transforming growth factor-β receptor blockade augments the effectiveness of adoptive T cell therapy of established solid cancers. Clin Cancer Res (2008) 14(12):3966-3974.
48. Bodmer S, Strommer K, Frei K, Siepl C, de Tribolet N, Heid I, Fontana A: Immunosuppression and transforming growth factor-β in glioblastoma. Preferential production of transforming growth factor-β 2. J Immunol (1989) 143(10): 3222-3229. (Pubitemid 20010149)
49. Xiao BG, Link H: Immune regulation within the CNS. J Neuro Sci (1998) 157(1):1-12
50. Ueda R, Fujita M, Zhu X, Sasaki K, Kastenhuber ER, Kohanbash G, McDonald HA, Harper J, Lonning S, Okada H: Systemic inhibition of transforming growth factor-β in glioma-bearing mice improves the therapeutic efficacy of glioma-associated antigen peptide vaccines. Clin Cancer Res (2009) 15(21): 6551-6559.
51. Terabe M, Ambrosino E, Takaku S, O'Konek JJ, Venzon D, Lonning S, McPherson JM, Berzofsky JA: Synergistic enhancement of CD8+ T cell-mediated tumor vaccine efficacy by an anti-transforming growth factor-β monoclonal antibody. Clin Cancer Res (2009) 15(21):6560-6569.
52. Takaku S, Terabe M, Ambrosino E, Peng J, Lonning S, McPherson JM, Berzofsky JA: Blockade of TGF-β enhances tumor vaccine efficacy mediated by CD8+ T cells. Int J Cancer (2009) 126(7):1666-1674.
53. Levéen P, Larsson J, Ehinger M, Cilio CM, Sundler M, Sjöstrand LJ, Holmdahl R, Karlsson S: Induced disruption of the transforming growth factor β type II receptor gene in mice causes a lethal inflammatory disorder that is transplantable. Blood (2002) 100(2):560-568. (Pubitemid 34761120)
54. Garber K: Companies waver in efforts to target transforming growth factor β in cancer. J Nat Cancer Inst (2009) 101(24): 1664-1667.
55. Yang YA, Dukhanina O, Tang B, Mamura M, Letterio JJ, MacGregor J, Patel SC, Khozin S, Liu ZY, Green J, Anver MR et al: Lifetime exposure to a soluble TGF-β antagonist protects mice against metastasis without adverse side effects. J Clin Invest (2002) 109(12):1607-1615. (Pubitemid 34663523)
56. Ruzek M, Hawes M, Pratt B, McPherson J, Ledbetter S, Richards S, Garman R: Minimal effects on immune paramaters following chronic anti-TGF-β monoclonal antibody administration to normal mice. Immunopharmacol Immunotoxicol (2003) 25(2): 235-237.
57. Arteaga C: Inhibition of TGFβ signaling in cancer therapy. Curr Opin Genet Devel (2006) 16:30-37. (Pubitemid 43089609)
58. Forrester E, Chytil A, Bierie B, Aakre M, Gorska AE, Sharif-Afshar AR, Muller WJ, Moses HL: Effect of conditional knockout of the type II TGF-β receptor gene in mammary epithelia on mammary gland development and polyomavirus middle T antigen induced tumor formation and metastasis. Cancer Res (2005) 65(6):2296-2302. (Pubitemid 40490139)
59. Kanzler S, Meyer E, Lohse AW, Schirmacher P, Henninger J, Galle PR, Blessing M: Hepatocellular expression of a dominantnegative mutant TGF-β type II receptor accelerates chemically induced hepatocarcinogenesis. Oncogene (2001) 20(36):5015-5024. (Pubitemid 32769791)
60. Huntley SP, Davies M, Matthews JB, Thomas G, Marshall J, Robinson CM, Eveson JW, Paterson IC, Prime SS: Attenuated type II TGF-β receptor signalling in human malignant oral keratinocytes induces a less differentiated and more aggressive phenotype that is associated with metastatic dissemination. Int J Cancer (2004) 110(2):170-176. (Pubitemid 38580386)
61. Mythreye K, Blobe GC: The type III TGF-β receptor regulates epithelial and cancer cell migration through β-arrestin2-mediated activation of Cdc42. Proc Natl Acad Sci USA (2009) 106(20):8221-8226.
62. Lee JD, Hempel N, Lee NY, Blobe GC: The type III TGF-p receptor suppresses breast cancer progression through GIPC-mediated inhibition of TGF-β signaling. Carcinogenesis (2009) 31(2):175-183.
63. You HJ, How T, Blobe GC: The type III transforming growth factor-β receptor negatively regulates nuclear factor i B signaling through its interaction with β-arrestin2. Carcinogenesis (2009) 30(8):1281-1287.
64. Li M, Flavell R: TGF-β: A master of all T cell trades. Cell (2008) 134(3):392-404.
65. Hannigan A, Smith P, Kalna G, Lo Nigro C, Orange C, O'Brien DI, Shah R, Syed N, Spender LC, Herrera B, Thurlow JK et al: Epigenetic downregulation of human disabled homolog 2 switches TGF-β from a tumor suppressor to a tumor promoter. J Clin Invest (2010) 120(8):2842-2857.