New Gene and Cell-Based Therapies for Lung Cancer

Raj K. Batra; Sherven Sharma; Steven M. Dubinett

doi:10.1055/s-2000-9455

Seminars in Respiratory and Critical Care Medicine, Table of Contents

Semin Respir Crit Care Med 2000; Volume 021(Number 05): 463-472
DOI: 10.1055/s-2000-9455

New Gene and Cell-Based Therapies for Lung Cancer

Raj K. Batra¹ , Sherven Sharma² , Steven M. Dubinett³

¹Division of Pulmonary and Critical Care Medicine, GLA-VAHCS, UCLA School of Medicine and Member, Jonsson Comprehensive Cancer Center
²Department of Medicine, Division of Pulmonary and Critical Care Medicine, West Los Angeles VA Medical Center, UCLA School of Medicine
³UCLA/Wadsworth Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, GLA-VAHCS, UCLA School of Medicine and Member, Jonsson Comprehensive Cancer Center, Los Angeles, California

Abstract

ABSTRACT

Lung cancer is the leading cause of cancer-related mortality in men and women in the United States, in part, because of the poor treatment options available. New treatment strategies that specifically target discreet steps in the molecular and cellular pathogenesis of this disease are under development. This review highlights many of the basic defects that result in the cellular transformation and subsequent progression of lung cancer, and how the understanding of those fundamental defects lead to the formulation of rational gene-based or cell-based therapies.

KEYWORD

Lung cancer - gene therapy - immunotherapy

Full Text

References

REFERENCES

1 Parker S, Davis K, Wingo P, Ries L, Heath C J. Cancer statistics by race and ethnicity. CA Cancer J Clin . 1998; 48 31-48
2 Ramanathan R, Belani C. Chemotherapy for advanced non-small cell lung cancer: Past, present and future. Semin Oncol . 1997; 24 440-454
3 Salgia R, Skarin A T. Molecular abnormalities in lung cancer. J Clin Oncol . 1998; 16 1207-1217
4 Carbone D. The biology of lung cancer. Semin Oncol . 1997; 24 388-401
5 Sethi T. Science, medicine, and the future. Lung cancer. Br Med J . 1997; 314 652-655
6 Nishio M, Koshikawa T, Kuroishi T. Prognostic significance of abnormal p53 accumulation in primary, resected non-small-cell lung cancers. J Clin Oncol . 1996; 14 497-502
7 Kern S, Pietenpol J, Thiagalingam S, Seymour A, Kinzler K, Vogelstein B. Oncogenic forms of p53 inhibit p53-regulated gene expression. Science . 1992; 256 827-830
8 Kern J A, Schwartz D A, Nordberg J E. p185neu expression in human lung adenocarcinomas predicts shortened survival. Cancer Res . 1990; 50 5184-5187
9 Roth J, Nguyen D, Lawrence D. Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer. Nature Med . 1996; 2 985-991
10 Qazilbash M, Xiao X, Cowan K, Walsh C. Cancer gene therapy using a novel adeno-associated virus vector expressing human wild-type p53. Gene Ther . 1997; 4 675-682
11 Takahashi T, Carbone D, Takahashi T. Wild-type but not mutant p53 suppresses the growth of human lung cancer cells bearing multiple genetic lesions. Cancer Res . 1992; 52 2340-2343
12 Freeman S M, Abboud C N, Whartenby K A. The ``bystander effect'': Tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res . 1993; 53 5274-5283
13 Nishizaki M, Fujiwara T, Tanida T. Recombinant adenovirus expressing wild-type p53 is antiangiogenic: A proposed mechanism for bystander effect. Clin Cancer Res . 1999; 5 1015-1023
14 Chen H, Carbone D. p53 as a target for anti-cancer immunotherapy. Mol Med Today . 1997; 3 160-167
15 Vierboom M, Nijman H, Offringa R. Tumor eradication by wild-type p53-specific cytotoxic T lymphocytes. J Exp Med . 1997; 186 695-704
16 Swisher S G, Roth J A, Nemunaitis J. Adenovirus-mediated p53 gene transfer in advanced non-small-cell lung cancer. J Natl Cancer Inst . 1999; 91 763-771
17 Bischoff J R, Kirn D H, Williams A. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science . 1996; 274 373-376
18 Heise C, Sampson-Johannes A, Williams A, McCormick F, Von Hoff D, Kirn D. ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nature Med . 1997; 3 639-645
19 Hall A R, Dix B R, O'Carroll S J, Braithwaite A W. p53-dependent cell death/apoptosis is required for a productive adenovirus infection. Nat Med . 1998; 4 1068-1072
20 Harada J N, Berk A J. p53-Independent and -dependent requirements for E1B-55K in adenovirus type 5 replication. J Virol . 1999; 73 5333-5344
21 Rothmann T, Hengstermann A, Whitaker N J, Scheffner M, zur Hausen H. Replication of ONYX-015, a potential anticancer adenovirus, is independent of p53 status in tumor cells. J Virol . 1998; 72 9470-9478
22 Gibbs J B, Oliff A, Kohl N E. Farnesyltransferase inhibitors: Ras research yields a potential cancer therapeutic. Cell . 1994; 77 175-178
23 Mukhopadhyay T, Tainsky M, Cavender A. Specific inhibition of K-ras expression and tumorigenicity of lung cancer cells by antisense RNA. Cancer Res . 1991; 51 1744-1748
24 Roth J. Modification of mutant K-ras gene expression in non-small cell lung cancer (NSCLC). Hum Gene Ther . 1996; 7 875-889
25 Yamamoto T, Ikawa S, Akiyama T. Similarity of protein encoded by the human c-erbB-2 gene to the epidermal growth factor receptor. Nature . 1986; 319 230-234
26 Noguchi M, Murahami M, Bennett W. Biologic consequences of over-expression of a transfected c-erbB-2 gene in immortalized human bronchial epithelial cells. Cancer Res . 1993; 53 2035-2043
27 Deshane J, Siegal G, Alvarez R. Targeted tumor killing via an intracellular antibody against erbB-2. J Clin Invest . 1995; 96 2980-2989
28 Shapiro G I, Edwards C D, Kobzik L. Reciprocal Rb inactivation and p16INK4 expression in primary lung cancers and cell lines. Cancer Res . 1995; 55 505-509
29 Craig C, Kim M, Ohri E. Effects of adenovirus-mediated p16INK4A expression on cell cycle arrest are determined by endogenous p16 and Rb status in human cancer cells. Oncogene . 1998; 16 265-272
30 Pezzella F, Turley H, Kuzu I. bcl-2 Protein in non-small cell lung carcinoma. NEJM . 1993; 329 690-694
31 Ziegler A, Luedke G H, Fabbro D, Altmann K H, Stahel R A, Zangemeister-Wittke U. Induction of apoptosis in small-cell lung cancer cells by an antisense oligodeoxynucleotide targeting the Bcl-2 coding sequence. J Natl Cancer Inst . 1997; 89 1027-1036
32 Fearon E, Pardoll D, Itaya T. Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell . 1990; 60 397-403
33 Allione A, Consalvo M, Nanni P. Immunizing and curative potential of replicating and nonreplicating murine mammary adenocarcinoma cells engineered with interleukin (IL)-2, IL-4, IL-6, IL-7, IL-10, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and gamma-interferon gene or admixed with conventional adjuvants. Cancer Research . 1994; 54 6022-6026
34 Bottazzi B, Walter S, Govoni D, Colotta F, Mantovani A. Monocyte chemotactic cytokine gene transfer modulates macrophage infiltration, growth, and susceptibility to IL-2 therapy of a murine melanoma. J Immunol . 1992; 148 1280-1285
35 Colombo M P, Ferrari G, Stoppacciaro A. Granulocyte colony-stimulation factor (G-CSF) gene transfer suppress tumorigenicity of a murine adenocarcinoma in vivo. J Exp Med . 1991; 173 889-897
36 Heike Y, Takahashi M, Kanegae Y, Sato Y, Saito I, Saijo N. Interleukin-2 gene transduction into freshly isolated lung adenocarcinoma cells with adenoviral vectors. Human Gene Ther . 1997; 8 1-14
37 Pardoll D M. Paracrine cytokine adjuvants in cancer immunotherapy. Annu Rev Immunol . 1995; 13 399-415
38 Zitvogel L, Mayordomo J I, Tjandrawan T. Therapy of murine tumors with tumor peptide-pulsed dendritic cells: Dependence on T cells, B7 costimulation, and T helper cell 1-associated cytokines. J Exp Med . 1996; 183 87-97
39 Zitvogel L, Tahara H, Robbins P. Cancer immunotherapy of established tumors with IL-12: Effective delivery by genetically engineered fibroblasts. J Immunol . 1995; 155 1393-1403
40 Dranoff G, Jaffee E, Lazenby A. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA . 1993; 90 3539-3543
41 Sharma S, Wang J, Huang M. Interleukin-7 gene transfer in non-small cell lung cancer decreases tumor proliferation, modifies cell surface molecule expression, and enhances antitumor reactivity. Can Gene Ther . 1996; 3 302-313
42 Sica D, Rayman P, Stanley J. Interleukin 7 enhances the proliferation and effector function of tumor-infiltrating lymphocytes from renal-cell carcinoma. International J Cancer . 1993; 53 941-947
43 Welch P A, Namen A E, Goodwin R G, Armitage R, Cooper M D. Human IL-7: A novel T cell growth factor. J Immunol . 1989; 143 3562-3567
44 Chazen G, Pereira G, Le Gros G, Gillis S, Shevach E. Interleukin 7 is a T cell growth factor. Proc Natl Acad Sci USA . 1989; 86 5923-5927
45 Jicha D L, Mule J J, Rosenberg S A. Interleukin 7 generates antitumor cytotoxic T lymphocytes against murine sarcomas with efficacy in cellular adoptive immunotherapy. J Exp Med . 1991; 174 1511-1515
46 Stotter H, Custer M C, Bolton E S, Guedez L, Lotze M T. IL-7 induces human lymphokine-activated killer cell activity and is regulated by IL-4. J Immunol . 1991; 146 150-155
47 Dubinett S M, Huang M, Dhanani S, Wang J, Beroiza T. Down-regulation of macrophage transforming growth factor-βmessenger RNA expression by interleukin-7. J Immunol . 1993; 151 6670-6680
48 Dubinett S, Huang M, Dhanani S. Down-regulation of murine fibrosarcoma transforming growth factor-β1 expression by interleukin 7. JNCI . 1995; 87 593-597
49 Miller P, Sharma S, Stolina M. Intratumoral administration of adenoviral interleukin-7 gene-modified dendritic cells augments specific antitumor immunity and achieves tumor eradication. Hum Gene Ther . 2000; 11 53-65
50 Sharma S, Miller P, Stolina M. Multi-component gene therapy vaccines for lung cancer: Effective eradication of established murine tumors in vivo with interleukin 7/herpes simplex thymidine kinase-transduced autologous tumor and ex vivo-activated dendritic cells. Gene Ther . 1997; 4 1361-1370
51 Huang M, Wang J, Lee P. Human non-small cell lung cancer cells express a type 2 cytokine pattern. Cancer Res . 1995; 55 3847-3853
52 Kobayashi M, Fitz L, Ryan M. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med . 1989; 170 827
53 Chan S H, Perussia B, Gupta J W. Induction of interferon γproduction by natural killer cell stimulatory factor: Characterization of the responder cells and synergy with other inducers. J Exp Med . 1991; 173 869
54 Chehimi J, Starr S, Frank I. Natural killer (NK) cell stimulatory factor increases the cytotoxic activity of NK cells from both healthy donors and human immunodeficiency virus-infected patients. J Exp Med . 1992; 175 789
55 Gately M K, Wolitzky A G, Quinn P M, Chizzonite R. Regulation of human cytolytic lymphocyte responses by interleukin-12. Cell Immunol . 1992; 143 127-142
56 Yao L, Sgadari C, Furuke K, Bloom E T, Teruya-Feldstein J, Tosato G. Contribution of natural killer cells to inhibition of angiogenesis by interleukin-12. Blood . 1999; 93 1612-1621
57 Angiolillo A, Sgadari C, Tosato G. A role for the interferon-inducible protein 10 in inhibition of angiogenesis by interleukin-12. Ann N Y Acad Sci . 1996; 795 158-167
58 Brunda M J, Luistro L, Warrier R R. Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med . 1993; 178 1223-1230
59 Nastala C L, Edington H D, McKinney T G. Recombinant IL-12 administration induces tumor regression in association with IFN-γproduction. J Immunol . 1994; 153 1697-1706
60 Haku T, Yanagawa H, Nabioullin R, Takeuchi E, Sone S. Interleukin-12-mediated killer activity in lung cancer patients. Cytokine . 1997; 9 846-852
61 Yoshino I, Goedegebuure P S, Peoples G E. HER2/neu-derived peptides are shared antigens among human non-small cell lung cancer and ovarian cancer. Cancer Res . 1994; 54 3387-3390
62 Restifo N P, Esquivel F, Kawakami Y. Identification of human cancers deficient in antigen processing. J Exp Med . 1993; 177 265-272
63 Huang A YC, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, Levitsky H. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science . 1994; 264 961-965
64 Caux C, Liu Y, Banchereau J. Recent advances in the study of dendritic cells and follicular dendritic cells. Immunol Today . 1995; 16 2-4
65 Steinman R M. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol . 1991; 9 271-296
66 Hsu F, Benike C, Fagnoni F. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nature Med . 1996; 2 52-58
67 Nestle F, Alijagic S, Gilliet M. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nature Med . 1998; 4 328-332
68 Ribas A, Butterfield L, McBride W. Genetic immunization for the melanoma antigen MART-1/Melan-A using recombinant adenovirus-transduced murine dendritic cells. Cancer Res . 1997; 57 2865-2869
69 Miller P W, Sharma S, Stolina M. Dendritic cells augment granulocyte-macrophage colony-stimulating factor (GM-CSF)/herpes simplex virus thymidine kinase-mediated gene therapy of lung cancer. Cancer Gene Ther . 1998; 5 380-389
70 Chouaib S, Assellin-Paturel C, Mami-Chouaib F, Caignard A, Blay J. The host-tumor immune conflict: From immunosuppression to resistance and destruction. Immunol Today . 1997; 18 493-497
71 Huang M, Stolina M, Sharma S. Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: Up-regulation of interleukin 10 and down-regulation of interleukin 12 production. Cancer Res . 1998; 58 1208-1216
72 Stolina M, Sharma S, Lin Y. Specific inhibition of cyclooxygenase 2 restores antitumor immunity by altering the balance of IL-10 and IL-12 synthesis. J Immunol . 2000; 164 361-370
73 Handel-Fernandez M E, Ching X, Herbert L M, Lopez D M. Down-regulation of IL-12, not a shift from a T helper-1 to a T helper-2 phenotype, is responsible for impaired IFN-γ production in mammary tumor-bearing mice. J Immunol . 1997; 158 280-286
74 Alleva D G, Burger C J, Elgert K D. Tumor-induced regulation of suppressor macrophage nitric oxide and TNF-alpha production: Role of tumor-derived IL-10, TGF-beta and prostaglandin E2. J Immunol . 1994; 153 1674
75 Huang M, Sharma S, Mao J T, Dubinett S M. Non-small cell lung cancer-derived soluble mediators and prostaglandin E₂ enhance peripheral blood lymphocyte IL-10 transcription and protein production. J Immunol . 1996; 157 5512-5520
76 Bolon I, Devouassoux M, Robert C, Moro D, Brambilla C, Brambilla E. Expression of urokinase-type plasminogen activator, stromelysin 1, stromelysin 3, and matrilysin genes in lung carcinomas. Am J Pathol . 1997; 150 1619-1629
77 Garbisa S, Scagliotti G, Masiero L. Correlation of serum metalloproteinase levels with lung cancer metastasis and response to therapy. Cancer Res . 1992; 52 4548-4549
78 Kawano N, Osawa H, Ito T. Expression of gelatinase A, tissue inhibitor of metalloproteinases-2, matrilysin, and trypsin(ogen) in lung neoplasms: An immunohistochemical study. Hum Pathol . 1997; 28 613-622
79 Mari B, Anderson I, Mari S. Stromelysin-3 is induced in tumor/stroma cocultures and inactivated via a tumor-specific and basic fibroblast growth factor-dependent mechanism. J Biol Chem . 1998; 273 618-626
80 DeClerck Y, Perez N, Shimada H, Boone T, Langley K, Taylor S. Inhibition of invasion and metastatis in cells transfected with an inhibitor of metalloproteinases. Cancer Res . 1992; 52 701-708
81 Noel A, Lefebvre O, Maquoi E. Stromelysin-3 expression promotes tumor take in nude mice. J Clin Invest . 1996; 97 1924-1930
82 Skobe M, Rockwell P, Goldstein N, Vosseler S, Fusenig N. Halting angiogenesis suppresses carcinoma cell invasion. Nature Med . 1997; 3 1222-1227
83 Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat med . 1995; 1 27-31
84 Fontanini G, Vignati S, Lucchi M. Neoangiogenesis and p53 protein in lung cancer: Their prognostic role and their relation with vascular endothelial growth factor (VEGF) expression. Br J Cancer . 1997; 75 1295-1301
85 O'Reilly M S, Holmgren L, Shing Y. Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell . 1994; 79 315-328
86 O'Reilly M, Boehm T, Shing Y. Endostatin: And endogenous inhibitor of angiogenesis and tumor growth. Cell . 1997; 88 277-285
87 Rak J, Kerbel R. Treating cancer by inhibiting angiogenesis: New hopes and potential pitfalls. Cancer Metastasis Rev . 1996; 15 231-236
88 Cyster J. Chemokines and cell migration in secondary lymphoid organs. Science . 1999; 286 2098-2102
89 Ohta Y, Watanabe Y, Murakami S. Vascular endothelial growth factor and lymph node metastasis in primary lung cancer. Br J Cancer . 1997; 76 1041-1045
90 Arenberg D, Polverini P, Kunkel S. The role of CXC chemokines in the regulation of angiogenesis in non-small cell lung cancer. J Leukocyte Biol . 1997; 62 554-562
91 Arenberg D, Kunkel S, Polverini P, Glass M, Burdick M, Strieter R. Inhibition of Interleukin-8 reduces tumorigenesis of human non-small cell lung cancer in SCID mice. J Clin Invest . 1996; 97 2792-2802
92 Hynes R. Integrins: Versatility, modulation, and signaling in cell adhesion. Cell . 1992; 69 11-25
93 Leavesley P, Schwartz M, Rosenfeld M, Cheresh D. Integrin b1- and b3-mediated endothelial cell migration is triggered through distinct signaling mechanisms. J Cell Biol . 1993; 121 163-170
94 Brooks P, Montgomery A, Rosenfeld M. Integrin α_vβ₃ antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell . 1994; 79 1157-1164
95 Arap W, Pasqualini R, Ruoslahti E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science . 1998; 279 377-380
96 Wang C-Y, Mayo M W, Baldwin A SJ. TNF- and cancer therapy-induced apoptosis: Potentiation by inhibition of NF-κB. Science . 1996; 274 784-787
97 Batra R K, Guttridge D C, Brenner D A, Dubinett S M, Baldwin A S, Boucher R C. IkappaBalpha gene transfer is cytotoxic to squamous-cell lung cancer cells and sensitizes them to tumor necrosis factor-alpha-mediated cell death. Am J Respir Cell Mol Biol . 1999; 21 238-245
98 Kim J H, Kim S H, Brown S L, Freytag S O. Selective enhancement be an antiviral agent of the radiation-induced cell killing of human glioma cells transduced with HSV-tk gene. Cancer Res . 1994; 54 6053-6056
99 McBride W, Dougherty G. Radiotherapy for genes that cause cancer. Nature Med . 1995; 1 1215-1217
100 Hanna N, Mauceri H, Wayne J, Hallahan D, Kufe D, Weichselbaum R. Virally directed cytosine deaminase/5-fluorocytosine gene therapy enhances radiation response in human cancer xenografts. Cancer Res . 1997; 57 4205-4209
101 McIlwrath A, Vasey P, Ross G, Brown R. Cell cycle arrests and radiosensitivity of human tumor cell lines: Dependence on wild-type p53 for radiosensitivity. Cancer Res . 1994; 54 3718-3722
102 Gallardo D, Drazen Z E, McBride W H. Adenovirus-based Transfer of Wild-Type p53 Gene Increases Ovarian Tumor Radiosensitivity. Cancer Res . 1996; 56 4891-4893
103 Nguyen D, Spitz F, Yen N, Cristiano R, Roth J. Gene therapy for lung cancer: Enhancement of tumor suppression by a combination of sequential systemic cisplatin and adenovirus-mediated p53 gene transfer. J Thorac Cardiovasc Surg . 1996; 112 1372-1377
104 Boris-Lawrie K, Temin H. The retroviral vector. Replication cycle and safety considerations for retrovirus-mediated gene therapy. Ann NY Acad Sci . 1994; 716 59-70
105 Kay M, Liu D, Hoogerbrugge P. Gene therapy. Proc Natl Acad Sci USA . 1997; 94 12744-12746
106 Naldini L, Blomer U, Gallay P. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science . 1996; 272 263-267
107 Naldini L, Blomer U, Gage F, Trono D, Verma I. Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc Natl Acad Sci USA . 1996; 93 11382-11388
108 Kasahara N, Dozy A, Kan Y. Tissue-specific targeting of retroviral vectors through ligand-receptor interactions. Science . 1994; 266 1373-1376
109 Batra R, Olsen J, Pickles R, Hoganson S, Boucher R. Transduction of non-small cell lung cancer cells by adenoviral and retroviral vectors. Am J Respir Cell Mol Biol . 1998; 18 402-410
110 Mastrangeli A, Danel C, Rosenfeld M. Diversity of airway epithelial cell targets for in vivo recombinant adenovirus-mediated gene transfer. J Clin Invest . 1993; 91 225-234
111 Dai Y, Schwarz E, Gu D, Zhang W, Sarvetnick N, Verma I. Cellular and humoral immune responses to adenoviral vectors containing factor IX gene: Tolerization of factor IX and vector antigens allows for long-term expression. Proc Natl Acad Sci USA . 1995; 92 1401-1405
112 Yang Y, Li Q, Ertl H, Wilson J. Cellular and humoral immune responses to viral antigens create barriers to long-directed gene therapy with recombinant adenoviruses. J Virol . 1995; 69 2004-2015
113 Yang Y, Su Q, Wilson J. Role of viral antigens in destructive cellular immune responses to adenovirus vector-transduced cells in mouse lungs. J Virol . 1996; 70 7209-7212
114 Mitani K, Graham F, Caskey C, Kochanek S. Rescue, propagation, and partial purification of a helper virus-dependent adenovirus vector. Proc Natl Acad Sci USA . 1995; 92 3854-3858
115 Jooss K, Yang Y, Wilson J M. Cyclophosphomide diminishes inflammation and prolongs transgene expression following delivery of adenoviral vectors to mouse liver and lung. Hum Gene Ther . 1996; 7 1555-1566
116 Bergelson J M, Cunningham J A, Droguett G. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science . 1997; 275 1320-1323
117 Douglas J T, Rogers B E, Rosenfeld M E, Michael S I, Feng M, Curiel D T. Targeted gene delivery by tropism-modified adenoviral vectors. Nat Biotechnol . 1996; 14 1574-1578
118 Wickham T, Roelvink P, Brough D, Kovesdi I. Adenovirus targeted to heparan-containing receptors increases its gene delivery efficiency to multiple cell types. Nature Biotechnol . 1996; 14 1570-1573
119 Tursz T, Cesne A, Baldeyrou P. Phase I study of a recombinant adenovirus-mediated gene transfer in lung cancer patients. J Natl Cancer Inst . 1996; 88 1857-1863
120 Gahery-Segard H, Molinier-Frenkel V, Le Boulaire C. Phase I trial of recombinant adenovirus gene transfer in lung cancer: Longitudinal study of the immune responses to transgene and viral products. J Clin Invest . 1997; 100 2218-2226
121 Sterman D, Treat J, Litzky L. Adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir gene therapy in patient with localized malignancy: Results of a phase I clinical trial in malignant mesothelioma. Hum Gene Ther . 1998; 9 1083-1092
122 Batra R, Olsen J, Hoganson D, Caterson B, Boucher R. Retroviral gene transfer is inhibited by chondroitin sulfate proteoglycans/glycosaminoglycans in malignant pleural effusions. J Biol Chem . 1997; 272 11736-11743
123 Crystal R G. Transfer of genes to humans: Early lessons and obstacles to success. Science . 1995; 270 404-410
124 Jain R K. Barriers to drug delivery in solid tumors. Sci Am . 1994; 271 58-65