A Phase I Multicenter Study of E1A Gene Therapy for Patients with Metastatic Breast Cancer and Epithelial Ovarian Cancer That Overexpresses HER-2/neu or Epithelial Ovarian Cancer. M.D. Anderson Cancer Center, Houston, Texas

Human Gene Therapy

Volumn 9, Issue 12, 1998, Pages 1775-1798

  Hortobagyi, Gabriel N ^a   Carey, Mary M ^b   Hung, Mien Chie ^a   Lopez Berestein, Gabriel ^a  

^a Department of Breast Medical Oncology ^*  (United States)

^b Sr Clinical Research Associate   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

E1A PROTEIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2;

ARTICLE; BREAST TUMOR; CLINICAL PROTOCOL; CLINICAL TRIAL; FEMALE; GENE THERAPY; GENETICS; HUMAN; METASTASIS; MULTICENTER STUDY; OVARY TUMOR; PATHOLOGY; PHASE 1 CLINICAL TRIAL;

ADENOVIRUS E1A PROTEINS; BREAST NEOPLASMS; CLINICAL PROTOCOLS; FEMALE; GENE THERAPY; HUMANS; NEOPLASM METASTASIS; OVARIAN NEOPLASMS; RECEPTOR, ERBB-2;

EID: 0032504347     PISSN: 10430342     EISSN: 15577422     Source Type: Journal    
DOI: 10.1089/hum.1998.9.12-1775     Document Type: Article

References (89)

1. Boring, C.C., Squires, T.S., Tong, T.: Cancer Statistics. 1992. Ca-A Cancer Journal for Physicians 42 (1992) 19–38.
2. Piver, M., Baker, T., Piedmonte, M. and Sandecki, A.: Epidemiology and etiology of ovarian cancer. Seminars in Oncology 18(3) (1991) 177–185.
3. Creasman, W. and DiSaia, P.: Screening in ovarian cancer. Am. J. Obstet. Gynecol. 165(1) (1991) 7–10.
4. Yan, D. H., Chang, L. S. and Hung, M. C., Repressed expression of the HER-2/c-erbB-2 proto-oncogene by the adenovirus E1A gene products. Oncogene 6 (1991) 343–345.
5. Yan, D. H. and Hung, M. C., Identification and characterization of a novel enhancer for the rat neu promoter. Mol. Cell. Biol. 11 (1991)1875–1882.
6. Yu, D., Hamada, J., Zhang, H., Nicolson, G.L. and Hung, M. C., Mechanisms of c-erbB-2/neu oncogene-induced metastasis and repression of metastatic properties by adenovirus 5 E1A gene products. Oncogene 7 (1992a) 2263–2270.
7. Yu, D., Wolf, J.K., Scanlon, M., Price, J.E. and Hung, M. C., Enhanced c-erbB-2/neu expression in human ovarian cancer cells correlates with more severe malignancy that can be suppressed by E1A. Cancer Res. 53 (1993) 891–898.
8. Bargmann, C.I., Hung, M.C. and Weinberg, R.A.: The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature 319(1986) 226–230.
9. Hung, M.C., Schechter, A.L., Churay, P.Y.M., Stern, D.F. and Weinberg, R.A.: Molecular cloning of the neu gene: Absence of gross structural alterations in oncogenic alleles. Proc. Natl. Acad. Sci. U.S.A. 83 (1986) 261–264.
10. Yamamoto, T.M., Ikawa, S., Akjiyana, T., Semba, K., Normura, N., Miyajima, N., Saito, T. and Toyoshima, K.: Similarity of protein encoded by the human c-erbB-2 gene to the epidermal growth factor receptor. Nature 319 (1986) 230–234.
11. Coussens, L., Yang-Feng, T.L., Liao, Y.C., Chen, E., Gray, A., McGrath, J., Seeburg, P.H., Libermann, T.A., Schlessinger, J., Francke, U., Lavinson, A. and Ullrich, A.: Tyrosine kinase receptor with extensive homology to the EGF receptor shares chromosomal location with the neu oncogene. Science 230 (1985) 132–1138.
12. Bargmann, C.I., Hung, M.C., and Weinberg, R.A.: Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185. Cell 45 (1986) 649–657.
13. Nikitin, A., Ballering, L.A., Lyons, J. and Rajewsky, M.F.; Early mutation of the neu (c-erbB-2) gene during ethylnitrosourea-induced oncogenesis in the rat Schwann cell lineage. Proc. Natl. Acad. Sci. U.S.A. 88 (1991) 9939–9943.
14. Schechter, A.L., Hung, M.C., Vaidyanathan, L., Decker, S., Drebin, J., Greene, M.I. and Weinberg, R.A.: The neu gene: An erb-B-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science 229 (1985) 976–978.
15. Boni-Schnetzler, M. and Pilch, P.F.: Mechanism of epidermal growth factor receptor autophosphorylation and high-affinity binding. Proc. Natl. Acad. Sci. 84 (1987) 7832–7836.
16. Weiner, D.B., Liu, J., Cohen, J.A., Williams, W.V. and Greene, M.I.: A point mutation in the neu oncogene mimics ligand induction of receptor aggregation. Nature 339 (1989) 230–231.
17. Wada, T., Qian, X. and Greene, M.I.: Intermolecular association of the p185neu protein and EGF receptor modulates EGF receptor function. Cell 61 (1990) 1339–1347.
18. Dobashi, K., Davis, J.G., Mikami, Y., Freeman, J.K., Hamuro, J. and Greene, M.I.: Characterization of a new/c-erbB-2 protein-specific activating factor. Proc. Natl. Acad. Sci. USA. 88 (1991) 8582–8586.
19. Holmes, W.E., Sliwkowski, M.X., Akita, R.W., Henzel, W.J., Lee, J., Park, J.W., Yansura, D., Abadi, N., Raab, H., Lewis, G.D., Shepard, H.M., Kuang, W.J., Wood, W.I., Goeddel, D.V. and Vandlen, R.L.: Identification of Heregulin, a Specific Activator of p185erbB2. Science. 256 (1992) 1205–1210.
20. Lupu, R., Colomer, R., Zugmaier, G., Sarup, J., Shepard, M., Slamon, D. and Lippman, M.E.: Direct interaction of a ligand for the erbB-2 oncogene product with the EGF receptor and p185erbB2. Science 249 (1990) 1552–1555.
21. Peles, E., Bacus, S.S., Koski, R.A., Lu, H.S., Wen, D., Ogden, S.G., Levy, R.B. and Yarden, Y.: Isolation of the Neu/HER-2 Stimulatory Ligand: A 44 kd Glycoprotein That Induces Differentiation of Mammary Tumor Cells. Cell 69 (1992) 205–216.
22. Shan, R., Matsuda, S., Ichino, M. and Yamamoto, T.: Detection of the ligand activity of the c-erbB-2 protein in calf serum. Jpn. J. Cancer Res. 83 (1992) 15–19.
23. Bargmann, C.I., and Weinberg, R.A.: Increased tyrosine activity associated with the protein encoded by the activated neu oncogene. Proc. Natl. Acad. Sci. U.S.A. 85 (1988) 5394–5398.
24. Wen, D., E. Peles, R. Cupples, S.V. Suggs, S.S. Bacus, Y. Luo, G. Trail, S. Hu, S.M. Silbiger, R. Ben Levy, R.A. Koski, H.S. Lu, and Yarden, Y.: Neu Differentiation Factor: A Transmembrane Glycoprotein Containing an EGF Domain and an Immunoglobulin Homology Unit. Cell 69 (1992) 559–572.
25. Samanta, A., LeVea, C.M., Dougall, W.C., Qian, X. and Greene, M.I.: Ligand and p185c-neu density govern receptor interactions and tyrosine kinase activation. Proc. Natl. Acad. Sci. U.S.A. 91 (1994) 1711–1715.
26. Saya, H., Ara, S., Lee, P., Ro, J. and Hung, M.C.: Direct sequencing analysis of transmembrane region of human neu gene by polymerase chain reaction. Mol. Carcinogenesis 3 (1990) 198–201.
27. Lemoine, N.R., Staddon, S., Dickson, C. and Gullick, W.J.: Absence of activating transmembrane mutations in the c-erbB-2 proto-oncogene in human breast cancer. Oncogene 5 (1990) 237–239.
28. Kamitani, H., Mariyama, M., Hori, T. and Nishimura, S.: Mutations in transmembrane domain of c-erbB-2 gene in human malignant tumors of the central nervous system. Neurological Res. 14 (1992)236–240.
29. Bargmann, C.I. and Weinberg, R.A.: Increased tyrosine kinase activity associated with the protein encoded by the activated neu oncogene. Proc. Natl. Acad. Sci. U.S.A. 85 (1988) 5394–5398.
30. Stern, D.F., Kamps, M.P. and Cao, H. (1988) Oncogenic activation of p185neu stimulates tyrosine phosphorylation in vivo. Mol. Cell. Biol. 8 3969–3973.
31. di Diore, P., Pierce, J., Kraus, M., Segatto, O., King, C., and Aaronson, S.: erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science 237 (1987) 178–182.
32. Hudzaik, R., Schlessinger, J. and Ullrich, A.: Increased expression of the putative growth factor receptor p 185 HER-2 causes transformation and tumorigenesis of NIH-3T3 cells. Proc. Natl. Acad. Sci. U.S.A. (1987)7159–7163.
33. Hung, M.C., Yan, D.H. and Zhao, X.: Amplification of the proto-neu oncogene facilitates oncogenic activation by a single point mutation. Proc. Natl. Acad. Sci., U.S.A. 86 (1989) 2545–2548.
34. Bouchard, L., Lamarre, L., Tremblay, P.J. and Jolicoeur, P.: Stochastic appearance of mammary tumors in transgenic mice carrying the MMTV/c-neu oncogene. Cell 57 (1989) 931–936.
35. Muller, W.I., Sinn, E., Pallengale, P.K., Wallace, R. and Leder, P.: Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 54 (1988) 105–115.
36. Guy, L.T., Webster, M.A., Schaler, M., Parsons, T.J., Cardiff, R.A. and Muller, W.J.: Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc. Natl. Acad. Sci. U.S.A. 89 (1992) 10578–10582.
37. Slamon, D.J., Clark, G.M., Wong, S.G., Levin, W.J., Ullrich, A. and McGuire, W.L.: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235 (1987) 177–182.
38. McCann, A.H., Dervan, P.A., O'Regan, M., Codd, M.B., Gullick, W.I., Tobin, B.M.J., and Camey, D.N.: Prognostic significance of c-erbB-2 and estrogen receptor status in human breast cancer. Cancer Res. 51 (1991) 3296–3303.
39. Vijver, M.V.D., Bersselaar, R.V.D., Devilee, P., Comelisse, C., Peterse, J. and Nusse, R.: Amplification of the neu (c-erbB-2) oncogene in human mammary tumors is relatively frequent and is often accompanied by amplification of the linked c-erbA oncogene. Mol. Cell. Biol. 7 (1987) 2019–2023.
40. Gusterson, B., Gelber, R., Goldhirsch, A., Price, K., Save-Soderberg, J., Anbazhagan, R., Styles, J., Rudenstam, C.M., Golouh, R., Reed, R., Martinez-Tello, F., Tiltman, A., Torhorst, J., Grigolato, P., Bettelheim, R., Neville, A., Burki, K., Castiglione, M., Collins, J., Lindtner, J. and Senn, H.J.: prognostic importance of c-erbB-2 expression in breast cancer. J Clin. Oncol. 10(7) (1992) 1049–1056.
41. Toikkanen, S., Helin, H., Isola, J. and Joensuu, H.: Prognostic significance of HER-2 oncoprotein expression in breast cancer: a 30-year follow-up. J. Clin. Oncol. 10 (1992) 1044–1048.
42. Slamon, D.J., Godolphin, W., Jones, L.A., Holt, J.A., Wong, S.G., Keith, D.E., Levin, W.J., Stuart, S.G., Udove, J., Ullrich, A. and Press, M.F.: Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244 (1989) 707–712.
43. Berchuck, A., Rodriguez, G., Kinney, R., Soper, J., Dodge, R., Clarke-Pearson, D. and Bast C., Jr.: Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease. Am. J. Obstet. Gynecol. 164 (1/1) (1991) 15–21.
44. Berchuck, A., Kamel, A., Whitaker, R., Kems, B., Olt, G., Kinney, R., Soper, J.T., Dodge, R., Clarke-Pearson, D.L., Marks, P., McKenzie, S., Yin, S. and Bast C., Jr.: Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res. 50 (1990) 4087–4091.
45. Zhang, X., Silva, E., Gershenson, D. and Hung, M.C.: Amplification and rearrangement of c-erbB proto-oncogenes in cancer of human female genital tract. Oncogene 4 (1989) 985–989.
46. Berns, E., Klun, J., Henzen-Longmans, S., Rodenburg, C., Van Der Burg, M. and Foekens, J.: Receptors for hormones and growth factors and onco-gene amplification in human ovarian cancer. Int. J. Cancer 52 (1992) 218–224.
47. Hung, M.C., Zhang, X., Yan, D.H., Zhang, H.Z., He, G.P., Zhang, T.Q. and Shi, D.R.: Aberrant expression of the c-erbB-2/neu protooncogene in ovarian cancer. Cancer Letters 61 (1992) 95–103.
48. Tyson, F., Boyer, C., Kaufman, R., O'Briant, K., Cram, G., Crews, J., Soper, J., Daly, L., Fowler, Jr., W., Haskill, J. and Bast, Jr., R.: Expression and amplification of the WR-2/neu (c-erb-2) protooncogene in epithelial ovarian tumors and cell lines. Am. J. Obstet. Gynecol. 165 (3) (1991) 640–646.
49. Schneider, P.M., Hung, M.C., Chiocca, S.M., Manning, J., Zhao, X., Fang, K. and Roth, J.A.: Differential expression of the c-erbB-2 gene in human small cell and non-small cell lung cancer. Cancer Res. 49 (1989) 4968–4971.
50. Shi, D., He, G., Cao, S., Pan, W., Zhang, H.Z., Yu, Z. and Hung, M.C.: Overexpression of the c-erbB-2/neu-encoded p185 protein in primary lung cancer. Mol. Carcinogenesis 5 (1992) 213–218.
51. Weiner, D.B., Nordberg, J., Robinson, R., Nowell, P.C., Gazdar, A., Greene, M.I., Williams, W.V., Cohen, J.A. and Kern, J.A.: Expression of the neu gene-encoded protein (P185neu) in human non-small cell carcinomas of the lung. Cancer Res. 50 (1990) 421–425.
52. D'Emilia, J., Bulovas, K., D'Ercole, K., Wolf, B., Steele, G.J. and Summerhayes, I.C.: Expression of the c-erbB-2 gene product (p185) at different stages of neoplastic progression in the colon. Oncogene. 4 (1989) 1233–1239.
53. Park, J.B., Rhim, J.S., Park, S.C., Kimm, S.W. and Kraus, M.H.: Amplification, overexpression, and rearrangement of the erbB-2 protooncogene in primary human stomach carcinomas. Cancer Res. 49 (1989) 6005–6009.
54. Yokota, J., T. Yamamoto, N. Miyajima, K. Toyoshima, N. Nomura, H. Sakakoto, T. Yoshida, M. Terada, and Sugimura, T.: Genetic alterations of the c-erbB-2 oncogene occur frequently in tubular adenocarcinoma of the stomach and are often accompanied by amplification of the v-erbA homologue. Oncogene 2 (1988) 283–287.
55. Hou, L., Shi, D., Tu, S.M., Zhang, H.Z., Hung, M.C. and Ling, D.: Oral cancer progression of the c-erbB-2/neu proto-oncogene in ovarian cancer. Cancer Letters 61 (1992) 95–103.
56. Mitra, A.B., Murty, V.V.V.S., Pratap, M., Sodhani, P. and Chaganti, R.S.K.: ERBB-2 (HER-2/neu) oncogene is frequently amplified in squamous cell carcinoma of the uterine cervix. Cancer Res. 54 (1994) 637–639.
57. Yonemura, Y., Ninomiya, I., Ohoyama, S., Fushida, S., Kimura, H., Tsugawa, K., Kamata, T., Yamaguchi, A., Miyazaki, I., Enodou, Y., Tanaka, M., Sasaki, T.: Correlation of c-erbB-2 protein expression and lymph node status in early gastric cancer. Oncology 49 (1992) 363–367.
58. Yu, D. and Hung, M.C.: Expression of activated rat neu oncogene is sufficient to induce experimental metastasis in 3T3 cells. Oncogene 6(1991) 1991–1996.
59. Yusa, K., Sugimoto, Y., Yamori, T., Yamamoto, T., Toyoshima, K. and Tsuruo, T.: Low metastatic potential of clone from murine colon adenocarcinoma 26 increased by transfection of activated c-erbB-2 gene. J. Natl. Cancer. Inst. 82 (1990) 1633–1636.
60. Yu, D., Wang, S.S., Dulski, K.M., Tsai, C.M., Nicolson, G.L. and Hung, M.C.: C-erbB-2/neu overexpression enhances metastatic potential of human lung cancer cells by induction of metastasis-associated properties. Cancer Res. 54 (1994) 3260–3266.
61. Tsai, C.M., Chang, K.T., Perng, R.P., Mitsudomi, T., Chen, M.H., Kadoyama, C. and Gazdar, A.F.: Correlation of intrinsic chemoresistance of non-small-cell lung cancer cell lines with HER-2/neu gene expression but not with ras gene mutations. J. Natl. Cancer Inst. 85 (11) (1993) 897–901.
62. Tooze, J.: DNA tumor viruses. (1981) In Molecular Biology of Tumor Viruses, 2nd Edition (Cold Spring Harbor, New York: Cold Spring Harbor Laboratory).
63. Yu, D., Suen, T.C., Yan, D.H., Chang, L.S. and Hung, M.C.: Transcriptional repression of the neu protooncogene by the adenovirus 5 E1A gene products. Proc. Natl. Acad. Sci. U.S.A. 87 (1990) 4499–4503.
64. Yu, D., Scorsone, K. and Hung, M.C.: Adenovirus type 5 E1A gene products act as transformation suppressors of the neu oncogene. Mol. Cell. Biol. 11 (1991) 1745–1750.
65. Land, H., Parada, L.F. and Weinberg, R.A.: Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature (London) 304 (1983) 596–602.
66. Gao, X., and Huang, L.: A novel cationic liposome reagent for efficient transfection of mammalian cells. Biochem. Biophy. Res. Commun. 179 (1991) 280–285.
67. Nabel, G.J., Nabel, E.G., Yang, Z.Y., Fox, B.A., Plautz, G.E., Gao, X., Huang, L., Shu, S., Gordon, D., Chang, A.E.: Direct gene transfer with DNA-liposome complexes in melanoma: Expression, biological activity, and lack of toxicity in humans. Proc. Natl. Acad. Sci. 90(1993) 11307–11311.
68. Caplen, N.J., Alton, E.W., Middleton, P.G., Dorin, J.R. Stevenson, B.J. Gao, X., Durham, S.R., Jeffrey, P.K., Hodson, M.E., Coutelle, C., Huang, L., Porteous, D.J., Williamson, R., Geddes, D.M.: Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Nature Medicine 1 (1995) 39–46.
69. Gomez-Foix, A.M., Coats, W.S., Baque, S., Alam, T., Gerard, R.D. and Newgard, C.B.: Adenovirus-mediated transfer of the muscle glycogen phosphorylase gene into hepatocytes confers altered regulation of glycogen metabolism. J. Biol. Chem. 267 (1992) 25129–25134.
70. Frisch S.M. Antioncogenic effect of adenovirus E1a in human tumor cells. Proc Natl Acad Sci USA. 1991; 88:9077–9081.
71. Frisch S.M. E1a induces the expression of epithelial characteristics. J Cell Biol. 1994; 127(4):1085–1096.
72. Frisch S.M., Dolter K.E. Adenovirus E1a-mediated tumor suppression by a c-erbB-2/neu-independent mechanism. Cancer Res. 1995;55:5551–5555.
73. Frisch S.M., Francis H. Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol. 1994;124(4):619–626.
74. van Groningen J.J.M., Comelissen I.M.A.H., van Muijen G.N.P., Bloemers H.P.J., Swart G.W.M. Simultaneous suppression of progression marker genes in the highly malignant human melanoma cell line BLM after transfection with the adenovirus-5 E1A gene. Biochem Biophys Res Com. 1996; 225:808–816.
75. Kraus, M.H., N.C. Popescu, S.C. Ambaugh, and King, C.R.: Over-expression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms. EMBO J. 6 (1987) 605–610.
76. Berger, M.S., Locher, G.W., Saurer, S., Gullick, W.J., Waterfield, M.D., Groner, B. and Hynes, N.E.: Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res. 48 (1988) 1238–1243.
77. Pasleau, F., Grooteclaes, M. and Gol-Winkler R.: Expression of the c-erbB-2 gene in the BT474 human mammary tumor cell line: measurement of the c-erbB-2 mRNA half-life. Oncogene 8 (1993) 849–854.
78. Hollywood, D.P. and Hurst, H.C.: A novel transcription factor, OB2–1, is required for overexpression of the proto-oncogene c-erbB-2 in mammary tumor lines. EMBO J 12 (1993) 2369–2375.
79. Miller, S.J., Suen, T.C., Sexton, T.B. and Hung, M.C.: Mechanism of deregulated HER-2/neu expression in breast cancer cell lines. Int. J. Oncology. 4 (1994) 599–608.
80. Suen, T.C., and Hung, M.C.: Multiple cis- and trans-acting elements involved in regulation of the neu gene. Mol. Cell. Biol. 10 (1990) 6306–6315.
81. White, M.R.A., and Hung, M.C.: Cloning and characterization of the mouse neu promoter. Oncogene 7 (1992) 677–683.
82. Hudson, L.G., Ertl., A.P. and Gill, G.N.: Structure and inducible regulation of the human c-erbB-2/neu promoter. J. Biol. Chem. 265 (1990) 4389–4393.
83. Zhao, X.Y. and Hung, M.C.: Negative autoregulation of the neu gene is mediated by a novel enhancer. Mol. Cell. Biol. 12 (1992) 2739–2748.
84. Russell, K.S. and Hung, M.C.: Transcriptional repression of the neu protooncogene by estrogen stimulated estrogen receptor. Cancer Res. 52 (1992) 6624–6629.
85. Matin, A., and Hung, M.C.: Negative regulation of the neu promoter by the SV 40 large T antigen. Cell Growth & Differ. 4 (1993) 1051–1056.
86. Yu, D., Matin, A. and Hung, M.C.: The retinoblastoma gene product suppresses neu oncogene-induced transformation via transcriptional repression of neu. J. Biol. Chem. 267 (1992) 10203–10206.
87. Matin, A. and Hung, M.C.: The retinoblastoma gene product, Rb, represses neu expression through two regions within the neu regulatory sequence. Oncogene 9 (1994) 1333–1339.
88. Grooteclaes, M., Francoise, P., Huguette, D., Berzi, P. Albert, A., and Winkler-Gol, R.: The 6-kilobase c-erbB-2 promoter contains positive and negative regulatory elements functional in human mammary cell lines. Cancer Res. 54 (1994) 4193–4199.
89. Yu, D., Matin, A., Xia, W., Sorgi, F., Huang, L., Hung, M.C.: Liposome-mediated E1A gene transfer as therapy for ovarian cancer that overexpresses HER-2/neu. In Press.