Long term follow up: Phase i trial of "bi-shRNA furin/GMCSF DNA/ autologous tumor cell" immunotherapy (FANG™) in advanced cancer

Journal of Vaccines and Vaccination

Volumn 4, Issue 8, 2013, Pages

  Senzer, Neil ^a,b,c,d   Barve, Minal ^c   Nemunaitis, Jacklyn ^a   Kuhn, Joseph ^e   Melnyk, Anton ^f   Beitsch, Peter ^d   Magee, Mitchell ^g   Oh, Jonathan ^c   Bedell, Cynthia ^a   Kumar, Padmasini ^b   Rao, Donald D ^b   Pappen, Beena O ^b   Wallraven, Gladice ^b   Charles Brunicardi, F ^h   Maples, Phillip B ^b   Nemunaitis, John ^a,b,c,d  

^a Mary Crowley Cancer Research Centers   (United States)

^b GRADALIS INC   (United States)

^c TEXAS ONCOLOGY   (United States)

^d MEDICAL CITY DALLAS HOSPITAL   (United States)

^e WLS Surgical Associates PA   (United States)

^f Texas Cancer Center   (United States)

^g Cardiovascular Specialty Associates of North Texas PA   (United States)

^h UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Cancer; Clinical; RNA interference; Vaccine

Indexed keywords

EID: 84892150536     PISSN: None     EISSN: 21577560     Source Type: Journal    
DOI: 10.4172/2157-7560.1000209     Document Type: Article

References (79)

1. Senzer N, Barve M, Kuhn J, Melnyk A, Beitsch P, et al. (2012) Phase I trial of "bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell" vaccine (FANG) in advanced cancer. Mol Ther 20: 679-686.
2. Maples PB, Kumar P, Yu Y, Wang Z, Jay CM, et al. (2010) FANG Vaccine: Autologous Tumor Vaccine Genetically Modified to Express GM-CSF and Block Production of Furin. BioProcessing Journal 8: 4-14.
3. Rao DD, Maples PB, Senzer N, Kumar P, Wang Z, et al. (2010) Enhanced target gene knockdown by a bifunctional shRNA: a novel approach of RNA interference. Cancer Gene Ther 17: 780-791.
4. Fox BA, Schendel DJ, Butterfield LH, Aamdal S, Allison JP, et al. (2011) Defining the critical hurdles in cancer immunotherapy. J Transl Med 9: 214.
5. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, et al. (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366: 883-892.
6. Willimsky G, Blankenstein T (2005) Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature 437: 141-146.
7. von Bubnoff D, Bausinger H, Matz H, Koch S, Häcker G, et al. (2004) Human epidermal langerhans cells express the immunoregulatory enzyme indoleamine 2,3-dioxygenase. J Invest Dermatol 123: 298-304.
8. Belladonna ML, Volpi C, Bianchi R, Vacca C, Orabona C, et al. (2008) Cutting edge: Autocrine TGF-beta sustains default tolerogenesis by IDO-competent dendritic cells. J Immunol 181: 5194-5198.
9. Pallotta MT, Orabona C, Volpi C, Vacca C, Belladonna ML, et al. (2011) Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells. Nat Immunol 12: 870-878.
10. Olivares J, Kumar P, Yu Y, Maples PB, Senzer N, et al. (2011) Phase I trial of TGF-beta 2 antisense GM-CSF gene-modified autologous tumor cell (TAG) vaccine. Clin Cancer Res 17: 183-192.
11. Wheler J, Tsimberidou AM, Hong D, Naing A, Falchook G, et al. (2012) Survival of 1,181 patients in a phase I clinic: the MD Anderson Clinical Center for targeted therapy experience. Clin Cancer Res 18: 2922-2929.
12. Chiong B, Wong R, Lee P, Delto J, Scotland R, et al. (2004) Characterization of long-term effector-memory T-cell responses in patients with resected high-risk melanoma receiving a melanoma Peptide vaccine. J Immunother 27: 368-379.
13. Arens R, Schoenberger SP (2010) Plasticity in programming of effector and memory CD8 T-cell formation. Immunol Rev 235: 190-205.
14. Prehn RT, Main JM (1957) Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst 18: 769-778.
15. Kripke ML (1974) Antigenicity of murine skin tumors induced by ultraviolet light. J Natl Cancer Inst 53: 1333-1336.
16. Yang JC, Perry-Lalley D, Rosenberg SA (1990) An improved method for growing murine tumor-infiltrating lymphocytes with in vivo antitumor activity. J Biol Response Mod 9: 149-159.
17. Barth RJ Jr, Mulé JJ, Spiess PJ, Rosenberg SA (1991) Interferon gamma and tumor necrosis factor have a role in tumor regressions mediated by murine CD8+ tumor-infiltrating lymphocytes. J Exp Med 173: 647-658.
18. Anichini A, Mazzocchi A, Fossati G, Parmiani G (1989) Cytotoxic T lymphocyte clones from peripheral blood and from tumor site detect intratumor heterogeneity of melanoma cells. Analysis of specificity and mechanisms of interaction. J Immunol 142: 3692-3701.
19. Topalian SL, Solomon D, Rosenberg SA (1989) Tumor-specific cytolysis by lymphocytes infiltrating human melanomas. J Immunol 142: 3714-3725.
20. Van den Eynde B, Hainaut P, Hérin M, Knuth A, Lemoine C, et al. (1989) Presence on a human melanoma of multiple antigens recognized by autologous CTL. Int J Cancer 44: 634-640.
21. Darrow TL, Slingluff CL Jr, Seigler HF (1989) The role of HLA class I antigens in recognition of melanoma cells by tumor-specific cytotoxic T lymphocytes. Evidence for shared tumor antigens. J Immunol 142: 3329-3335.
22. Knuth A, Wölfel T, Klehmann E, Boon T, Meyer Zum Büschenfelde KH (1989) Cytolytic T-cell clones against an autologous human melanoma: specificity study and definition of three antigens by immunoselection. Proc Natl Acad Sci U S A 86: 2804-2808.
23. Dunn GP, Old LJ, Schreiber RD (2004) The three Es of cancer immunoediting. Annu Rev Immunol 22: 329-360.
24. Sporn MB, Roberts AB, Wakefield LM, Assoian RK (1986) Transforming growth factor-beta: biological function and chemical structure. Science 233: 532-534.
25. Massagué J (1987) The TGF-beta family of growth and differentiation factors. Cell 49: 437-438.
26. Border WA, Ruoslahti E (1992) Transforming growth factor-beta in disease: the dark side of tissue repair. J Clin Invest 90: 1-7.
27. Jachimczak P, Bogdahn U, Schneider J, Behl C, Meixensberger J, et al. (1993) The effect of transforming growth factor-beta 2-specific phosphorothioateanti-sense oligodeoxynucleotides in reversing cellular immunosuppression in malignant glioma. J Neurosurg 78: 944-951.
28. Baker JC, Harland RM (1997) From receptor to nucleus: the Smad pathway. Curr Opin Genet Dev 7: 467-473.
29. Heldin CH, Miyazono K, ten Dijke P (1997) TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 390: 465-471.
30. Stiles JD, Ostrow PT, Balos LL, Greenberg SJ, Plunkett R, et al. (1997) Correlation of endothelin-1 and transforming growth factor beta 1 with malignancy and vascularity in human gliomas. J Neuropathol Exp Neurol 56: 435-439.
31. Yingling JM, Datto MB, Wong C, Frederick JP, Liberati NT, et al. (1997) Tumor suppressor Smad4 is a transforming growth factor beta-inducible DNA binding protein. Mol Cell Biol 17: 7019-7028.
32. Merzak A, McCrea S, Koocheckpour S, Pilkington GJ (1994) Control of human glioma cell growth, migration and invasion in vitro by transforming growth factor beta 1. Br J Cancer 70: 199-203.
33. Jennings MT, Kaariainen IT, Gold L, Maciunas RJ, Commers PA (1994) TGF beta 1 and TGF beta 2 are potential growth regulators for medulloblastomas, primitive neuroectodermal tumors, and ependymomas: evidence in support of an autocrine hypothesis. Hum pathol 1994 25: 464-475.
34. Jennings MT, Pietenpol JA (1998) The role of transforming growth factor beta in glioma progression. J Neurooncol 36: 123-140.
35. Ashley DM, Kong FM, Bigner DD, Hale LP (1998) Endogenous expression of transforming growth factor beta1 inhibits growth and tumorigenicity and enhances Fas-mediated apoptosis in a murine high-grade glioma model. Cancer Res 58: 302-309.
36. Ashley DM, Sampson JH, Archer GE, Hale LP, Bigner DD (1998) Local production of TGF beta1 inhibits cerebral edema, enhances TNF-alpha induced apoptosis and improves survival in a murine glioma model. J Neuroimmunol 86: 46-52.
37. Constam DB, Philipp J, Malipiero UV, ten Dijke P, Schachner M, et al. (1992) Differential expression of transforming growth factor-beta 1,-beta 2, and-beta 3 by glioblastoma cells, astrocytes, and microglia. J Immunol 148: 1404-1410.
38. Levy L, Hill CS (2006) Alterations in components of the TGF-beta superfamily signaling pathways in human cancer. Cytokine Growth Factor Rev 17: 41-58.
39. Bierie B, Moses HL (2006) Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer 6: 506-520.
40. Eastham JA, Truong LD, Rogers E, Kattan M, Flanders KC, et al. (1995) Transforming growth factor-beta 1: comparative immunohistochemical localization in human primary and metastatic prostate cancer. Lab Invest 73: 628-635.
41. Friedman E, Gold LI, Klimstra D, Zeng ZS, Winawer S, et al. (1995) High levels of transforming growth factor beta 1 correlate with disease progression in human colon cancer. Cancer Epidemiol Biomarkers Prev 4: 549-554.
42. Jakowlew SB, Mathias A, Chung P, Moody TW (1995) Expression of transforming growth factor beta ligand and receptor messenger RNAs in lung cancer cell lines. Cell Growth Differ 6: 465-476.
43. Kong FM, Anscher MS, Murase T, Abbott BD, Iglehart JD, et al. (1995) Elevated plasma transforming growth factor-beta 1 levels in breast cancer patients decrease after surgical removal of the tumor. Ann Surg 222: 155-162.
44. Yamada N, Kato M, Yamashita H, Nistér M, Miyazono K, et al. (1995) Enhanced expression of transforming growth factor-beta and its type-I and type-II receptors in human glioblastoma. Int J Cancer 62: 386-392.
45. Eder IE, Stenzl A, Hobisch A, Cronauer MV, Bartsch G, et al. (1996) Transforming growth factors-beta 1 and beta 2 in serum and urine from patients with bladder carcinoma. J Urol 156: 953-957.
46. Bodmer S, Strommer K, Frei K, Siepl C, de Tribolet N, et al. (1989) Immunosuppression and transforming growth factor-beta in glioblastoma. Preferential production of transforming growth factor-beta 2. J Immunol 143: 3222-3229.
47. Chen TC, Hinton DR, Yong VW, Hofman FM (1997) TGF-B2 and soluble p55 TNFR modulate VCAM-1 expression in glioma cells and brain derived endothelial cells. J Neuroimmunol 73: 155-161.
48. Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA (2006) Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol 24: 99-146.
49. Scarlett UK, Rutkowski MR, Rauwerdink AM, Fields J, Escovar-Fadul X, et al. (2012) Ovarian cancer progression is controlled by phenotypic changes in dendritic cells. J Exp Med 209: 495-506.
50. Thomas DA, Massagué J (2005) TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell 8: 369-380.
51. Rook AH, Kehrl JH, Wakefield LM, Roberts AB, Sporn MB, et al. (1986) Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness. J Immunol 136: 3916-3920.
52. Kasid A, Bell GI, Director EP (1988) Effects of transforming growth factor-beta on human lymphokine-activated killer cell precursors. Autocrine inhibition of cellular proliferation and differentiation to immune killer cells. J Immunol 141: 690-698.
53. Tsunawaki S, Sporn M, Ding A, Nathan C (1988) Deactivation of macrophages by transforming growth factor-beta. Nature 334: 260-262.
54. Hirte H, Clark DA (1991) Generation of lymphokine-activated killer cells in human ovarian carcinoma ascitic fluid: identification of transforming growth factor-beta as a suppressive factor. Cancer Immunol Immunother 32: 296-302.
55. Ruffini PA, Rivoltini L, Silvani A, Boiardi A, Parmiani G (1993) Factors, including transforming growth factor beta, released in the glioblastoma residual cavity, impair activity of adherent lymphokine-activated killer cells. Cancer Immunol Immunother 36: 409-416.
56. Naganuma H, Sasaki A, Satoh E, Nagasaka M, Nakano S, et al. (1996) Transforming growth factor-beta inhibits interferon-gamma secretion by lymphokine-activated killer cells stimulated with tumor cells. Neurol Med Chir (Tokyo) 36: 789-795.
57. Yamaguchi Y, Tsumura H, Miwa M, Inaba K (1997) Contrasting effects of TGFbeta 1 and TNF-alpha on the development of dendritic cells from progenitors in mouse bone marrow. Stem Cells 15: 144-153.
58. Geissmann F, Revy P, Regnault A, Lepelletier Y, Dy M, et al. (1999) TGF-beta 1 prevents the noncognate maturation of human dendritic Langerhans cells. J Immunol 162: 4567-4575.
59. Steinman RM, Hawiger D, Liu K, Bonifaz L, Bonnyay D, et al. (2003) Dendritic cell function in vivo during the steady state: a role in peripheral tolerance. Ann N Y Acad Sci 987: 15-25.
60. Ashcroft GS (1999) Bidirectional regulation of macrophage function by TGFbeta. Microbes Infect 1: 1275-1282.
61. Takeuchi M, Alard P, Streilein JW (1998) TGF-beta promotes immune deviation by altering accessory signals of antigen-presenting cells. J Immunol 160: 1589-1597.
62. Du C, Sriram S (1998) Mechanism of inhibition of LPS-induced IL-12p40 production by IL-10 and TGF-beta in ANA-1 cells. J Leukoc Biol 64: 92-97.
63. 2 signaling plays a critical role in promoting alternative macrophage activation. BMC Immunol 13: 31.
64. O'Sullivan T, Saddawi-Konefka R, Vermi W, Koebel CM, Arthur C, et al. (2012) Cancer immunoediting by the innate immune system in the absence of adaptive immunity. J Exp Med 209: 1869-1882.
65. Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, et al. (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proceedings of the National Academy of Sciences of the United States of America 90: 3539-3543.
66. Mach N, Dranoff G (2000) Cytokine-secreting tumor cell vaccines. Curr Opin Immunol 12: 571-575.
67. Senzer NN, Kaufman HL, Amatruda T, Nemunaitis M, Reid T, et al. (2009) Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol 27: 5763-5771.
68. Spitler LE, Grossbard ML, Ernstoff MS, Silver G, Jacobs M, et al. (2000) Adjuvant therapy of stage III and IV malignant melanoma using granulocytemacrophage colony-stimulating factor. J Clin Oncol 18: 1614-1621.
69. Rini BI, Weinberg V, Bok R, Small EJ (2003) Prostate-specific antigen kinetics as a measure of the biologic effect of granulocyte-macrophage colonystimulating factor in patients with serologic progression of prostate cancer. J Clin Oncol 21: 99-105.
70. Anderson PM, Markovic SN, Sloan JA, Clawson ML, Wylam M, et al. (1999) Aerosol granulocyte macrophage-colony stimulating factor: a low toxicity, lungspecific biological therapy in patients with lung metastases. Clin Cancer Res 5: 2316-2323.
71. Huang AY, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, et al. (1994) Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 264: 961-965.
72. Young JW, Inaba K (1996) Dendritic cells as adjuvants for class I major histocompatibility complex-restricted antitumor immunity. J Exp Med 183: 7-11.
73. Pulendran B, Lingappa J, Kennedy MK, Smith J, Teepe M, et al. (1997) Developmental pathways of dendritic cells in vivo: distinct function, phenotype, and localization of dendritic cell subsets in FLT3 ligand-treated mice. J Immunol 159: 2222-2231.
74. Shen Z, Reznikoff G, Dranoff G, Rock KL (1997) Cloned dendritic cells can present exogenous antigens on both MHC class I and class II molecules. J Immunol 158: 2723-2730.
75. Murtaza A, Kuchroo VK, Freeman GJ (1999) Changes in the strength of costimulation through the B7/CD28 pathway alter functional T cell responses to altered peptide ligands. International immunology 11: 407-416.
76. Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, et al. (1997) CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science 278: 1626-1629.
77. Yamaguchi H, Furukawa K, Fortunato SR, Livingston PO, Lloyd KO, et al. (1990) Human monoclonal antibody with dual GM2/GD2 specificity derived from an immunized melanoma patient. Proc Natl Acad Sci U S A 87: 3333-3337.
78. Bendelac A, Rivera MN, Park SH, Roark JH (1997) Mouse CD1-specific NK1 T cells: development, specificity, and function. Annu Rev Immunol 15: 535-562.
79. Smyth MJ, Crowe NY, Hayakawa Y, Takeda K, Yagita H, et al. (2002) NKT cells-conductors of tumor immunity? Curr Opin Immunol 14: 165-171.