Conclusions
The experimental results from the use of gene transfer techniques for cancer therapy are promising but, at the same time, somewhat perplexing. Progress will depend on the further understanding of the biology of tumour interaction with the immune system, as this would be important for the development of optimal strategies for harnessing an effective immune response against tumours. On the other hand, extrapolation from laboratory models to human disease is limited and, therefore, there is a requirement for well-planned clinical studies. Although numerous viral and non-viral methods of gene transfer are available currently, in order to achieve realistic therapeutic efficacy for in vivo gene therapy of cancer there is a pressing need to improve on existing vectors. Hopefully, effort being directed at this objective will result in the development of safer, more highly efficient and well-targeted vectors which in turn will lead to the reality of wide clinical application.
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References
Addison CL, Braciak T, Ralston R, Muller WJ, Gauldie J, Graham FL (1995) Intratumoral injection of an adenovirus expressing interleukin 2 induces regression and immunity in a murine breast cancer model. Proc Natl Acad Sci USA 92: 8522
Ali M, Lemoine NR, Ring CJA (1994). The use of DNA viruses as vectors for gene therapy. Gene Ther 1: 367
Allison JP, Hurwitz AA, Leach DR (1995) Manipulation of costimulatory signals to enhance antitumor T-cell responses. Curr Opin Immunol 7: 682
Allison JP, Krummel MF (1995) The Yin and Yang of T cell costimulation. Science 270: 932
Azuma M, Ito D, Yagita H, Okumura K, Phillips JH, Lanier LL, Somoza C (1993) B70 antigen is a second ligand for CTLA-4 and CD28. Nature 366: 76
Bannerji R, Arroyo CD, Cordon-Cardo C, Gilboa E (1994) The role of IL-2 secreted from genetically modified tumor cells in the establishment of antitumor immunity. J Immunol 152: 2324
Barba D, Hardin J, Sadelain M, Gage F (1994) Development of anti-tumor immunity following thymidine kinase-mediated killing of experimental brain tumors. Proc Natl Acad Sci USA 91: 4348
Baskar S, Glimcher L, Nabavi N, Jones R, Ostrand-Rosenberg S (1995) Major histocompatibility complex class II+B7-1+ tumor cells are potent vaccines for stimulating tumor rejection in tumorbearing mice. J Exp Med 181: 619
Baum C, Hegewisch-Becker S, Eckert HG, Stocking C, Ostertag W (1995) Novel retroviral vectors for efficient expression of the multidrug resistance (mdr-1) gene in early hematopoietic cells. J Virol 69: 7541
Baum C, Margison GP, Eckert H-G, Fairbairn LJ, Ostertag W, Rafferty JA (1996) Gene transfer to augment the therapeutic index of anticancer chemotherapy. Gene Ther 3: 1
Bett AJ, Haddara W, Prevec L, Graham FL (1994) An efficient and flexible system for construction of adenovirus vectors with insertions or deletions in early regions 1 and 3. Proc Natl Acad Sci USA 91: 8802
Bi WL, Parysek LM, Wamick R, Stambrook PJ (1993) In vitro evidence that metabolic cooperation is responsible for the bystander effect observed with HSV tk retroviral gene therapy. Hum Gene Ther 4: 725
Blankenstein T (1994) Increasing tumour immunogenicity by genetic modification. Eur J Cancer 30A: 1182
Bluestone JA (1995) New perspectives of C1328-137-mediated T cell costimulation. Immunity 2: 555
Bonnekoh B, Greenhalgh DA, Bundman DS, Eckhardt JN, Longley MA, Chen SH, Woo SLC, Roop DR (1995) Inhibition of melanoma growth by adenovirul-mediated HSV thymidine kinase gene transfer in vivo. J Invest Dermatol 104: 313
Boon T, Cerottini J-C, Van den Eynde B, van der Bruggen P, Van Pel A (1994) Tumor antigens recognised by lymphocytes. Annu Rev Immunol 12: 337
Bronte V, Tsung K, Rao JB, Chen PW, Wang M, Rosenberg SA, Restifo NP (1995) IL-2 enhances the function of recombinant poxvirus-based vaccines in the treatment of established pulmonary metastases. J Immunol 154: 5282
Carducci MA, Ayyagari SR, Sanda MG, Simons JW (1995) Gene therapy for human prostate cancer. Cancer 75: 2013
Cavallo F, Giovarelli M, Gulino A, Vacca A, Stoppaciaro A, Modesti A, Forni G (1992) Role of neutrophils and CD4+ T lymphocytes in the primary and memory response to nonimmunogenic murine mammary adenocarcinoma made immunogenic by IL-2 gene. J Immunol 149: 3627
Cayeux S, Beck C, Aicher A, Dorken B, Blankenstein T (1995) Tumor cells cotransfected with interleukin-7 and B7.1 genes induce CD25 and CD28 on tumor-infiltrating T lymphocytes and are strong vaccines. Eur J Immunol 25: 2325
Cayeux S, Beck C, Dorken B, Blankenstein T (1996) Coexpression of interleukin-4 and B7.1 in murine tumor cells leads to improved tumor rejection and vaccine effect compared to single gene transfectants and a classical adjuvant. Hum Gene Ther 7: 525
Chen L, Ashe S, Brady WA, Hellstrom I, Hellstrom KE, Ledbetter JA, McGowan P, Linsley P (1992) Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell 71: 1093
Chen L, McGowan P, Ashe S, Johnson J, Li Y, Hellstrom I, Hellstrom K (1994) Tumor immunogenicity determines the effect of B7 costimulation on T cell-mediated tumor immunity. J Exp Med 179: 523
Chen S-H, Chen XHL, Wanf Y, Kosai K-I, Finegold MJ, Rich SS, Woo SLC (1995) Combination gene therapy for liver metastasis of colon carcinoma in vivo. Proc Natl Acad Sci USA 92: 2577
Clayman GL, El-Naggar AK, Roth JA, Zhang W-W, Goepfert H, Taylor DL, Liu T-J (1995) In vivo molecular therapy with p53 adenovirus for microscopic residual head and neck squamous carcinoma. Cancer Res 55: 1
Colak A, Goodman JC, Chen SH, Woo SLC, Grossman RG, Shine HD (1995) Adenovirus-mediated gene therapy in an experimental model of breast cancer metastatic to the brain. Hum Gene Ther 6: 1317
Colombo MP, Form G (1994) Cytokine gene transfer in tumor inhibition and tumor therapy: where are we now? Immunol Today 15: 48
Colombo MP, Modesti A, Parmiani G, Forni G (1992) Local cytokine availability elicits tumor rejection and systemic immunity through granulocyte-T-lymphocyte cross-talk. Cancer Res 52: 4853
Connors TA (1995) The choice of prodrgs for gene directed enzyme prodrug therapy of cancer. Gene Ther 2: 702
Conry RM, LoBuglio AF, Loechel F, Moore SE, Sumerel LA, Barlow DL, Curiel DT (1995) A carcinoembryonic antigen polynucleotide vaccine has in vivo antitumor activity. Gene Ther 2: 59
Consalvo M, Mullen CA, Modesti A, Musiani P, Allione A, Cavallo F, Giovarelli M, Forni G (1995) 5-Fluorocytosine-induced eradication of murine adenocarcinomas engineered to express the cytosine deaminase suicide gene requires host immune competence and leaves an efficient memory. J Immunol 154: 5302
Cordier L, Duffour M-T, Sabourin J-C, Lee MG, Cabannes J, Ragot T, Perricaudet M, Haddada H (1995) Complete recovery of mice from a pre-established tumor by direct intratumoral delivery of an adenovirus vector harboring the murine IL-2 gene. Gene Ther 2: 16
Cometta K, Morgan RA, Anderson WF (1991) Safety issues related to retroviral-mediated gene transfer in humans. Hum Gene Ther 2: 5
Cosset F-L, Takeuchi Y, Battini J-L, Weiss RA, Collins MKL (1995) High-titre packaging cells producing recombinant retroviruses resistant to human serum. J Virol 69: 7430
Coughlin CM, Wysocka M, Kurzawa HL, Lee WMF, Trinchieri G, Eck SL (1995) B7-1 and interleukin 12 synergistically induce effective antitumor immunity. Cancer Res 55: 4980
Cox AL, Skipper J, Chen Y, Henderson RA, LDarrow T, Shabanowitz J, Engelhard VH, Hunt DF, Slingluff CLJ (1994) Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines. Science 264: 716
Culver KW, Ram Z, Wallbridge S, Ishii H, Oldfield EH, Blaese RM (1992) In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science 256: 1550
Curiel DT, Agarwal S, Wagner E, Cotten M (1991) Adenovirs enhancement of transferrin-polylysine-mediated gene delivery. Proc Natl Acad Sci USA 88: 8850
Dalgleish AG (1994) The role of IL-2 in gene therapy. Gene Ther 1: 83
Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting antitumor immunity. Proc Natl Acad Sci USA 90: 3539
Eastham JA, Hall SJ, Sehgal I, Wang J, Timme TL, Yang G, Connell-Crowley L, Elledge SJ, Zhang W-W, Harper JW, Thompson TC (1995) In vivo gene therapy with p53 or p21 adenovirus for prostate cancer. Cancer Res 55: 5151
Fakhrai H, Shawler DL, Gjerset R, Naviaux RK, Koziol J, Royston I, Sobol RE (1995) Cytokine gene therapy with interleukin-2 transduced fibroblasts: effects of IL-2 dose on anti-tumor immunity. Hum Gene Ther 6: 591
Fearon ER, Pardoll DM, Itaya T, Golumbek P, Levitsky HI, Simons JW, Karasuyama H, Vogelstein B, Frost P (1990) Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 60: 397
Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielsen M (1987) Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci USA 84: 7413
Freeman GJ, Gribben JG, Boussiotis VA, Ng JW, Restivo VAJ, Lombard LA, Gray GS, Nadler LM (1993) Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. Science 262: 909
Freeman SM, Abboud CN, Whartenby KA, Packman CH, Koeplin DS, Moolten FL, Abraham GN (1993) The “bystander effect”: tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res 53: 5274
Friedmann T, Yee JK (1995) Pseudotyped retroviral vectors for studies of human gene therapy. Nature Med 1: 275
Fujiwara T, Cai DW, Georges RN, Mukhopadhyay T, Grimm EA, Roth JA (1994) Therapeutic effect of a retroviral wild-type p53 expression vector in an orthotopic lung cancer model. J Natl Cancer Inst 86: 1458
Gao X, Huang L (1995) Cationic liposome-mediated gene transfer. Gene Ther 2: 710
Gimmi CD, Freeman GJ, Gribben JG, Sugita K, Freedman AS, Morimoto C, Nadler LM (1991) Bcell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2. Proc Natl Acad Sci USA 88: 6575
Graham FL, Prevec L (1995) Methods for construction of adenovirus vectors. Mol Biotechnol 3: 207
Han X, Kasahara N, Kan YW (1995) Ligand-directed retroviral targeting of human breast cancer cells. Proc Natl Acad Sci USA 92: 9747
Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP (1992) CD28-mediated signalling costimulates murine T cells and prevents induction of anergy in T-cell clones. Nature 356: 607
Harris JD, Gutierrez AA, Hurst HC, Sikora K, Lemoine NR (1994) Gene therapy for cancer using tumour-specific prodrug activation. Gene Ther 1: 170
Hellstrom KE, Hellstrom I, Chen L (1995) Can co-stimulated tumor immunity be therapeutically efficacious? Immunol Rev 145: 123
Hock H, Dorsch M, Kunzendorf U, Uberla K, Qin Z, Diamanstein T, Blankenstein T (1993) Vaccination with tumor cells genetically engineered to produce different cytokines: effectivity not superior to a classical adjuvant. Cancer Res 53: 714
Huang AYC, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, Levitsky H (1994) Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 264: 961
Huber BE, Richards CA, Krenitsky TA (1991) Retroviral-mediated gene therapy for the treatment of hepatocellular carcinoma: an innovative approach for cancer therapy. Proc Natl Acad Sci USA 88: 8039
Hurford RK, Dranoff G, Mulligan RC, Tepper RI (1995) Gene therapy of metastatic cancer by in vivo retroviral gene targeting. Nature Genet 10: 430
Irvine KR, Rao JB, Rosenberg SA, Restifo NP (1996) Cytokine enhancement of DNA immunization leads to effective treatment of established pulmonary metastases. J Immunol 156: 238
Jenkins MK (1994) The ups and downs of T cell costimulation. Immunity 1: 443
Jin X, Nguyen D, Zhanh WW, Kyritsis AP, Roth JA (1995) Cell cycle arrest and inhibition of tumor cell proliferation by the pl6INK4 gene mediated by an adenovirus vector. Cancer Res 55: 3250
Jolly D (1994) Viral vector systems for gene therapy. Cancer Gene Ther 1: 51
Karp SE, Farber A, Salo JC, Hwu P, Jaffe G, Asher AL, Shiloni E, Restifo NP, Mule JJ, Rosenberg SA (1993) Cytokine secretion by genetically modified nonimmunogenic murine fibrosarcoma. J Immunol 150: 896
Kim TS, Cohen EP (1994) Interleukin-2-secreting mouse fibroblasts transfected with genomic DNA from murine melanoma cells prolong the survival of mice with melanoma. Cancer Res 54: 2531
Kim TS, Russell SJ, Collins MKL, Cohen EP (1993) Immunization with interleukin-2-secreting allogeneic mouse fibroblasts expressing melanoma-associated antigens prolongs the survival of mice with melanoma. Int J Cancer 55: 865
Kotin RM (1994) Prospects for the use of adeno-associated virus as a vector for human gene therapy. Hum Gene Ther 5: 793
Ledley FD (1995) Nonviral gene therapy: the promise of genes as pharmaceutical products. Hum Gene Ther 6: 1129
Leeson-Wood LA, Kim WH, Kleinman HK, Weintraub BD, Mixson AJ (1995) Systemic gene therapy with p53 reduces growth and metastases of a malignant human breast cancer in nude mice. Hum Gene Ther 6: 395
Linsley P, Brady W, Grosmaire L, Aruffo A, Damle NK, Ledbetter JA (1991) Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation. J Exp Med 173: 721
Linsley PS, Ledbetter JA (1993) The role of the CD28 receptor during T cell responses to antigen. Annu Rev Immunol 11: 191
Liu Y, Liggitt D, Zhong W, Tu G, Gaensler K, Debs R (1995) Cationic liposome-mediated intravenous gene delivery. J Biol Chem 270: 24864
Mandelboim O, Berke G, Fridkin M, Feldman M, Eisenstein M, Eisenbach L (1994) CTL induction by a tumour-associated antigen octapeptide derived from a routine lung carcinoma. Nature 369: 67
Melief JM, Kast WM (1993) Potential immunogenicity of oncogene and tumor suppressor gene products. Curt Opin Immunol 5: 709
Mercola D, Cohen JS (1995) Antisense approaches to cancer gene therapy. Cancer Gene Ther 2: 47
Miller A (1992) Retroviral vectors. Curr Top Microbiol Immunol 158: 1
Miller AD (1990) Retrovirus packaging cells. Hum Gene Ther 1: 5
Miller DG, Adam MA, Miller AD (1990) Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol 10: 4239
Mizoguchi H, O'Shea JJ, Longo DL, Loeffler CM, McVicar DW, Ochoa AC (1992) Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science 258: 1795
Moolten F (1986) Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res 46: 5276
Moolten FL (1994) Drug sensitivity (“suicide”) genes for selective cancer chemotherapy. Cancer Gene Ther 1: 279
Morgan RA, Couture L, Elroy-Stein O, Ragheb J, Moss B, Anderson WF (1992) Retroviral vectors containing putative internal ribosome entry sites: development of a polycistronic gene transfer system and applications to human gene therapy. Nucleic Acids Res 20: 1293
Mullen C, Kilstrup M, Blaese R (1992) Transfer of the bacterial gene for cytosine deaminase to mammalian cells confers lethal sensitivity to 5-fluorocytosine: a negative selection system. Proc Natl Acad Sci USA 89: 33
Mullen CA, Coale MM, Lowe R, Blaese RM (1994) Tumors expressing the cytosine deaminase suicide gene can be eliminated in vivo with 5-fluorocytosine and induce protective immunity to wild type tumor. Cancer Res 54: 1503
Nabel G, Nabel E, Yang Z-Y, Fox B, Plautz G, Gao X, Huang L, Shu S, Gordon D, Chang A (1993) Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans. Proc Natl Acad Sci USA 90: 11307
Nabel GJ, Chang A, Nabel EG, Plautz G, Fox BA, Huang L, Shu S (1992) Immunotherapy of malignancy by in vivo gene transfer into tumors. Hum Gene Ther 3: 399
Okamura H, Tsutsui H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K, Akita K, Namba M, Tanabe F, Konishi K, Fukuda S, Kurimoto M (1995) Cloning of a new cytokine that induces IFN-γ production by T cells. Nature 378: 88
Palmer TD, Rosman GJ, Osborne WRA, Miller AD (1991) Genetically modified skin fibroblasts persist long after transplantation but gradually inactivate introduced genes. Proc Natl Acad Sci USA 88: 1330
Pang S, Taneja S, Dardashti K, Cohan P, Kaboo R, Sokoloff M, Tso CL, Dekernion JB, Belldegrun AS (1995) Prostate tissue specificity of the prostate-specific antigen promoter isolated from a patient with prostate cancer. Hum Gene Ther 6: 1417
Pardoll D (1993) New strategies for enhancing the immunogenicity of tumors. Curt Opin Immunol 5: 719
Pardoll DM, Beckerleg AM (1995) Exposing the immunology of naked DNA vaccines. Immunity 3: 165
Plautz GE, Yang Z-Y, Wu B-Y, Gao X, Huang L, Nabel GJ (1993) Immunotherapy of malignancy by in vivo gene transfer into tumors. Proc Natl Acad Sci USA 90: 4645
Porgador A, Gansbacher B, Bannerji R, Tzehoval E, Gilboa E, Feldman M, Eisenbach L (1993) Anti-metastatic vaccination of tumor-bearing mice with IL-2-gene-inserted tumor cells. Int J Cancer 53: 471
Ram Z, Walbridge S, Heiss JD, Culver KW, Blaese RM, Oldfield EH (1994) In in vivo transfer of the human interleukin-2 gene: negative tumoricidal results in experimental brain tumors. J Neurosurg 80: 535
Rettinger SD, Kennedy SC, Wu X, Saylors RL, Hafenrichter DG, Flye MW, Ponder KP (1994) Liver-directed gene therapy: quantitative evaluation of promoter elements by using in vivo retroviral transduction. Proc Natl Acad Sci USA 91: 1460
Richards CA, Huber BE (1993) Generation of a transgenic model for retrovirus-mediated gene therapy for hepatocellular carcinoma is thwarted by the lack of transgene expression. Hum Gene Ther 4: 143
Rosenberg SA (1992) The immunotherapy and gene therapy of cancer. J Clin Oncol 10: 180
Russell SJ (1994) Replicating vectors for gene therapy of cancer: risks, limitations and prospects. Eur J Cancer 30A: 1165
Russell SJ, Brandenburger A, Flemming CL, Collins MKL, Rommelaere J (1992) Transformation-dependent expression of interleukin genes delivered by recombinant parvovirus. J Virol 66: 2821
Russell SJ, Eccles S, Flemming C, Johnson CA, Collins MKL (1991) Decreased tumorigenicity of a transplantable rat sarcoma following transfer and expression of an IL-2 cDNA. Int J Cancer 47: 244
Saito S, Bannerji R, Gansbacher B, Rosenthal F, Romanenko P, Heston W, Fair W, Gilboa E (1994) Immunotherapy of bladder cancer with cytokine gene-modified tumor vaccines. Cancer Res 54: 3516
Salmons B, Gunzburg WH (1993) Targeting of retroviral vectors for gene therapy. Hum Gene Ther 4: 129
Salvadori S, Gansbacher B, Wernick I, Tirelli S, Zier K (1995) B7-1 amplifies the response to interleukin-2-secreting tumor vaccines in vivo, but fails to induce a response by naive cells in vitro. Hum Gene Ther 6: 1299
Santodonato L, Ferrantini M, Gabriele L, Proietti E, Venditti M, Musiani P, Modesti A, Modica A, Lupton SD, Belardelli F (1996) Cure of mice with established metastatic Friend leukaemia cell tumors by a combined therapy with tumor cells expressing both interferon-al and herpes simplex thymidine kinase followed by ganciclovir. Hum Gene Ther 7: 1
Schmidt W, Schweighoffer T, Herbst E, Maass G, Berger M, Schilcher F, Schaffner G, Birnstiel ML (1995) Cancer vaccines: the interleukin 2 dosage effect. Proc Natl Acad Sci USA 92: 4711
Sorrentino BP, Brandt SJ, Bodine D, Gottesman M, Pastan I, Cline A, Nienhuis AW (1992) Selection of drug-resistant bone marrow cells in vivo after retroviral transfer of human MDR1. Science 257: 99
Sugaya S, Fujita K, Kikuchi A, Ueda H, Takakuwa K, Kodama S, Tanaka K (1996) Inhibition of tumor growth by direct intratumoral gene transfer of herpes simplex virus thymidine kinase gene with DNA-liposome complexes. Hum Gene Ther 7: 223
Sun WH, Burkholder JK, Sun J, Culp J, Turner J, GLu X, Pugh TD, Ershler WB, Yang N-S (1995) In vivo cytokine gene transfer by gene gun reduces tumor growth in mice. Proc Natl Acad Sci USA 92: 2889
Tahara H, Lotze MT (1995) Antitumor effects of interleukin-12 (IL-12): applications for the immunotherapy and gene therapy of cancer. Gene Ther 2: 96
Tahara H, Zitgovel L, Storkus WJ, Zeh HJ III, McKinney TG, Schreiber RD, Gubler U, Robbins PD, Lotze MT (1995) Effective eradication of established murine tumors with IL-12 gene therapy using a polycistronic retroviral vector. J Immunol 154: 6466
Takeuchi Y, Cosset FL, Lachmann PJ, Okada H, Weiss RA, Collins MKL (1994) Type C retrovirus inactivation by human complement is determined by both the viral genome and the producer cell. J Virol 68: 8001
Tepper RI, Mule JJ (1994) Experimental and clinical studies of cytokine gene-modified tumor cells. Hum Gene Ther 5: 153
Thierry AR, Lunardi-Iskandar Y, Bryant JL, Rabinovich P, Gallo RC, Mahan LC (1995) Systemic gene therapy: biodistribution and long-term expression of a transgene in mice. Proc Natl Acad Sci USA 92: 9742
Thompson CB (1995) Distinct roles for the costimulatory ligands B7-1 and B7-2 in T helper cell differentiation? Cell 81: 979
Townsend SE, Allison JP (1993) Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells. Science 259: 368
Trinchieri G (1995) Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol 13: 251
Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Felgner PL, Dwarki VJ, Gromkowski SH, Deck RR, DeWitt CM, Friedman A, Hawe LA, Leander KR, Artinez DM, Perry HC, Shiver JW, Montgomery DL, Liu MA (1993) Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259: 1745
Van den Eynde B, Brichard VG (1995) New tumor antigens recognized by T cells. Curt Opin Immunol 7: 674
Van Pel A, Boon T (1982) Protection against a nonimmunogenic mouse leukemia by an immunogenic variant obtained by mutagenesis. Proc Natl Acad Sci USA 79: 4718
Vieweg J, Rosenthal F, Bannerji R, Heston W, Fair W, Gansbacher B, Gilboa E (1994) Immunotherapy of prostate cancer in the Dunning rat model: use of cytokine gene modified tumor vaccines. Cancer Res 54: 1760
Vile R, Miller N, Chemajovsky Y, Hart I (1994) A comparison of the properties of different retroviral vectors containing the marine tyrosinase promoter to achieve transcriptionally targeted expression of the HSVtk or IL-2 genes. Gene Ther 1: 307
Vile R, Russell SJ (1994) Gene transfer technologies for the gene therapy of cancer. Gene Ther 1: 88
Vile RG (1994) Tumor-specific gene expression. Semin Cancer Biol 5: 429
Vile RG, Chong H, Dorudi S (1996) The immunosurveillance of cancer: specific and non-specific mechanisms. In: Dalgleish AC, Browning MJ (eds) Tumor immunology. Cambridge University Press, New York, pp 7–38
Vile RG, Diaz RM, Miller N, Mitchell S, Tuszyanski A, Russell SJ (1995) Tissue-specific gene expression from Mo-MLV retroviral vectors with hybrid LTRs containing the murine tyrosinase enhanancer/promoter. Virology 214: 307
Vile RG, Hart IR (1993) In vitro and in vivo targeting of gene expression to melanoma cells. Cancer Res 53: 962
Vile RG, Hart IR (1993) Use of tissue-specific expression of the herpes simplex thymidine kinase gene to inhibit growth of established murine melanomas following direct intratumoral injection of DNA. Cancer Res 53: 3860
Vile RG, Nelson JA, Castleden S, Chong H, Hart IR (1994) Systemic gene therapy of routine melanoma using tissue specific expression of the HSVtk gene involves an immune component. Cancer Res 54: 6228
Vile RG, Russell SJ (1995) Retroviruses as vectors. Br Med Bull 51: 12
Wagner E, Zatloukal K, Cotten M, Kirlappos H, Mechtler K, Curiel DT, Birnstiel ML (1992) Coupling of adenovirus to transfertin-polylysine/DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes. Proc Natl Acad Sci USA 89: 6099
Wang B, Merva M, Dang K, Ugen KE, Williams WV, Weiner DB (1995) Immunization by direct DNA inoculation induces rejection of tumor cell challenge. Hum Gene Ther 6: 407
Wei MX, Tamiya T, Hurford RK, Boviatsis EJ, Tepper RI, Chiocca A (1995) Enhancement of interleukin-4 mediated tumor regression in athymic mice by in situ retroviral gene transfer. Hum Gene Ther 1995: 437
Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247: 1465
Xiang Z, Ertl HC (1995) Manipulation of the immune response to a plasmid-encoded viral antigen by coinoculation with plasmids expressing cytokines. Immunity 2: 129
Yang G, Hellstrom KE, Hellstrom I, Chen L (1995) Antitumor immunity elicited by tumor cells transfected with B7-2, a second ligand for CD28/CTLA-4 costimulatory molecules. J Immunol 154: 2794
Yang Y, Nunes FA, Berencsi K, Furth EE, Gonczol E, Wilson JM (1994) Cellular immunity to viral antigens limits El-deleted adenoviruses for gene therapy. Proc Natl Acad Sci USA 91: 4407
Yang Z-Y, Perkins ND, Ohno T, Nabel EG, Nabel GJ (1995) The p21 cyclin-dependent kinase inhibitor suppresses tumorigenicity in vivo. Nature Med 1: 1052
Zhang Y, Mukhopadhyay T, Donehower LA, Georges RN, Roth JA (1993) Retroviral vector-mediated transduction of K-ras antisense RNA into human lung cancer cells inhibits expression of the malignant phenotype. Hum Gene Ther 4: 451
Zhu N, Liggitt D, Liu Y, Debs R (1993) Systemic gene expression after intravenous DNA delivery into adult mice. Science 261: 209
Zier KS, Gansbacher B (1995) The impact of gene therapy on T cell function in cancer. Hum Gene Ther 6: 1259
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Chong, H., Vile, R.G. New therapeutic approaches based on gene transfer techniques. Springer Semin Immunopathol 18, 149–170 (1996). https://doi.org/10.1007/BF00820663
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DOI: https://doi.org/10.1007/BF00820663