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. 1997;29(1):22–26. doi: 10.1007/BF02620270

Gene therapy in surgery

Part II: Application to septic shock and to organ transplantation

Gentherapeutische Strategien in der Chirurgie

M A Rogy 1,, Julie M Baumhofer 1, Britta Beinhauer 1, H Brandmeier 1, P Eisenburger 1, U M Losert 2, Ramila Philip 3
PMCID: PMC7101979  PMID: 32287331

Summary

Background: With the increasing body of knowledge in molecular biology, gene transfer respectively gene therapy becomes more and more a valid therapeutic option.

Methods: This is a critical review of gene therapy protocols for treatment of different types of cancer. Furthermore, the pathophysiological mechanism, therapeutically strategies as well as experimental approaches toward gene transfer in septic shock and organ transplantation are critically elucidated.

Results: Gene transfer as a therapeutic option was first successfully applied in children with severe combined immunodeficiency (SCID) in 1990. The majority of gene marking or gene therapy protocols approved for human clinical trials to date are related to the treatment of cancer. Besides viral vectors for brain tumors, non-viral vectors, liposomes particularly, with almost no side effects are increasingly used.

Conclusions: Different approaches of gene transfer in cancer patients are under investigation. Experimental data of septic shock treatment and rejection therapy of the allograft in organ recipients with gene transfer are encouraging for future applications in clinical trials.

Key-words: Gene therapy, cancer, septic shock, organ transplantation

Footnotes

Part I: Methods for Gene Transfer — Application to Cancer was published in Acta Chir Austriaca 1996;28:358–361.

References

  • (1).Blaese RM, Culver KW, Anderson WF. The ADA human gene therapy clinical protocol. Hum Gene Ther. 1990;1:331–362. doi: 10.1089/hum.1990.1.3-331. [DOI] [PubMed] [Google Scholar]
  • (2).Ascadi G, Dickson G, Love DR, et al. Human dystophin expression in mdx mice after intramuscular injection of DNA constructs. Nature. 1991;352:815–818. doi: 10.1038/352815a0. [DOI] [PubMed] [Google Scholar]
  • (3).Zhu N, Liggitt D, Debs R. Systemic gene expression after intravenous DNA delivery into adult mice. Science. 1993;261:209–211. doi: 10.1126/science.7687073. [DOI] [PubMed] [Google Scholar]
  • (4).Felgner PL, Gadek TR, Holm M, et al. Lipofection: a highly efficient, lipid mediated DNA transfection procedure. Proc Natl Acad Sci. 1987;84:7413–7417. doi: 10.1073/pnas.84.21.7413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (5).Philip R, Liggitt D, Philip M, Dazin B, Debs R. In vivo gene delivery. Efficient transfection of T lymphocytes in adult mice. J Biol Chem. 1993;268:16087–16090. [PubMed] [Google Scholar]
  • (6).Wu GY, Wu CH. Receptor mediated in vitro gene transformation by a soluble DNA carrier system. J Biol Chem. 1987;262:4429–4432. [PubMed] [Google Scholar]
  • (7).Wolff JA, Malone RW, Williams P, Chong W, Ascardi G, Jani A, Felgner P. Direct gene transfer into mouse muscle in vivo. Science. 1990;247:1465–1468. doi: 10.1126/science.1690918. [DOI] [PubMed] [Google Scholar]
  • (8).Dranoff G, Jaffee E, Lazenby A, Golumbeck B, et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocytemacrophage colony-stimulating factor stimulates potent, specific, and long lasting anti-tumor activity. Proc Natl Acad Sci USA. 1993;90:3539–3543. doi: 10.1073/pnas.90.8.3539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (9).Brenner MK, Furman WL, Santana VM, Bowman L, Meyer W. Phase I study of cytokine gene modified autologous neuroblastoma cells for treatment of relapsed/refractory neuroblastoma. Hum Gene Ther. 1992;3:665–676. doi: 10.1089/hum.1992.3.6-665. [DOI] [PubMed] [Google Scholar]
  • (10).Culver KW, Ram Z, Walbridge S, et al. In vivo gene transfer with retroviral producer cells for treatment of experimental brain tumors. Science. 1992;256:1550–1552. doi: 10.1126/science.1317968. [DOI] [PubMed] [Google Scholar]
  • (11).Gänsbacher B, Motzer R, Houghton A, Bander N. A pilot study of immunization with interleukin-2 secreting allogeneic HLA-A2 matched renal cell carcinoma cells in patients with advanced renal cell carcinoma. Hum Gene Ther. 1992;3:691–703. doi: 10.1089/hum.1992.3.6-691. [DOI] [PubMed] [Google Scholar]
  • (12).Golumbek PT, Lazenby AJ, Levitsky HI, et al. Treatment of established renal cell cancer by tumor cells engineered to secrete interleukin-4. Science. 1991;254:713–716. doi: 10.1126/science.1948050. [DOI] [PubMed] [Google Scholar]
  • (13).Kay MA, Li O, Liu TJ, et al. Hepatic gene therapy: Persistent expression of human α1-antitrypsin in mice after direct gene delivery in vivo. Hum Gene Ther. 1992;3:641–647. doi: 10.1089/hum.1992.3.6-641. [DOI] [PubMed] [Google Scholar]
  • (14).Yang NS, Burkholder J, Roberts B, Martinelli B, Mc Cabe D. In vivo and in vitro gene transfer to mammalian cells by particle bombardment. Proc Natl Acad Sci USA. 1990;87:9568–9572. doi: 10.1073/pnas.87.24.9568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (15).Blaese RM. Development of gene therapy for immunodeficiency: Adenosine deaminase deficiency. Pediatr Res. 1993;33(Suppl):S49–S55. doi: 10.1203/00006450-199304001-00010. [DOI] [PubMed] [Google Scholar]
  • (16).Blaese RM, Culver KW, Anderson WF, et al. Treatment of severe combined immunodeficiency disease (SCID) due to adenosine deaminase deficiency with CD34+ selected autologous peripheral blood cells transduced with a human ADA gene. Hum Gene Ther. 1993;4:521–527. doi: 10.1089/hum.1993.4.4-521. [DOI] [PubMed] [Google Scholar]
  • (17).Hsueh JL, Oiu X, Zhou J, et al. Clinical protocol of human gene transfer for hemophilia B. Hum Gene Ther. 1992;3:543–552. doi: 10.1089/hum.1992.3.5-543. [DOI] [PubMed] [Google Scholar]
  • (18).Beutler E. Gaucher disease:New molecular approaches to diagnoseis and treatment. Science. 1992;256:794–799. doi: 10.1126/science.1589760. [DOI] [PubMed] [Google Scholar]
  • (19).Harrison GS, Long CJ, Curiel TJ, Maxwell F, Maxwell IF. Inhibition of human immunodeficiency virus-I production resulting from transduction with a retrovirus containing an HIV-regulated diphteria toxin A chain gene. Hum Gene Ther. 1992;3:461–469. doi: 10.1089/hum.1992.3.5-461. [DOI] [PubMed] [Google Scholar]
  • (20).Crystal RG. Gene therapy strategies for pulmonary disease. Am J Med. 1992;92:44S–52S. doi: 10.1016/0002-9343(92)90607-D. [DOI] [PubMed] [Google Scholar]
  • (21).Dickson G, Love DR, Davies KE, Wells KE, Piper TA, Walsh FS. Human dystrophin gene transfer: production and expression of a functional recombinant DNA-based gene. Hum Genet. 1991;88:53–58. doi: 10.1007/BF00204929. [DOI] [PubMed] [Google Scholar]
  • (22).Jones SN, Grompe M, Munir M, Veres MI, Craigen G, Caskey CT. Ectopic correction of omithine transcarbamylase deficiency insparse mice. J Biol Chem. 1990;265:14684–14690. [PubMed] [Google Scholar]
  • (23).Shen L, Chen CW, Miller MD, et al. Recombinant virus vaccineinduced SIV-specific CDB+ cytotoxic T lymphocytes. Science. 1991;252:440–443. doi: 10.1126/science.1708168. [DOI] [PubMed] [Google Scholar]
  • (24).Rosenberg SA, Aerbersold P, Cornetta K, et al. Gene transfer into humans — Immunotherapy of patients with advanced melanoma, using tumor infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med. 1990;323:570–578. doi: 10.1056/NEJM199008303230904. [DOI] [PubMed] [Google Scholar]
  • (25).Rosenberg SA, Kasid A, Anderson WF, et al. TNF/TIL human gene therapy clinical protocol. Hum Gene Ther. 1990;1:443–462. [Google Scholar]
  • (26).Van Zee KJ, Stackpole SA, Montegut WJ, Rogy MA, et al. A human tumor necrosis factor (TNF) α mutant that binds exclusively to the p55 TNF receptor produces toxicity in the baboon. J Exp Med. 1994;179:1185–1191. doi: 10.1084/jem.179.4.1185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (27).Rosenberg SA, Anderson WF, Blaese RM, et al. Immunization of cancer patients using autologous cancer cells modified by insertion of the gene fo interleukin-2. Hum Gene Ther. 1992;3:75–90. doi: 10.1089/hum.1992.3.1-75. [DOI] [PubMed] [Google Scholar]
  • (28).Osanto S, Brouwenstyn N, Vaessen N, Figdor CG, Melief CJM, Schrier PI. Immunization with interleukin-2 transfected melanoma cells: A phase I–II study in patients with metastatic melanoma. Hum Gene Ther. 1993;4:323–330. doi: 10.1089/hum.1993.4.3-323. [DOI] [PubMed] [Google Scholar]
  • (29).Gaensbacher B, Houghton A, Livingston P. A pilot study of immunization with HLA-A2 matched allogeneic melanoma cells that secrete interleukin-2 in patients with metastatic melanoma. Hum Gene Ther. 1992;3:677–690. doi: 10.1089/hum.1992.3.6-677. [DOI] [PubMed] [Google Scholar]
  • (30).Nabel GJ, Chang A, Nabel EG, Plautz G. Immunotherapy of malignancy by in vivo gene transfer into tumors. Hum Gene Ther. 1992;3:399–410. doi: 10.1089/hum.1992.3.4-399. [DOI] [PubMed] [Google Scholar]
  • (31).Townsend SE, Alkison JP. Tumor rejection after direct costimulation of CDB+T cells by B7-transfected melanoma cells. Science. 1993;259:368–370. doi: 10.1126/science.7678351. [DOI] [PubMed] [Google Scholar]
  • (32).Moolten FL, Wells JM. Curability of tumors bearing herpes thymidine kinase genes transferred by retroviral vectors. J Nat Cancer Inst. 1990;82:297–300. doi: 10.1093/jnci/82.4.297. [DOI] [PubMed] [Google Scholar]
  • (33).Mullen CA. Metabolic suicide genes in gene therapy. Pharmacol Ther. 1994;63:199–207. doi: 10.1016/0163-7258(94)90046-9. [DOI] [PubMed] [Google Scholar]
  • (34).Helene C. Anti gene strategy: control of gene expression by triplexforming oligonucleotides. Anticancer Drug Design. 1991;6:569–584. [PubMed] [Google Scholar]
  • (35).Jacoby RF, Marshall DJ, Kailas S, Schlack S, Harms B, Love R. Genetic instability associated with adenoma to carcinoma progression in hereditary non-polyposis colon cancer (HNPCC) Gastroenterol. 1995;109:73–82. doi: 10.1016/0016-5085(95)90270-8. [DOI] [PubMed] [Google Scholar]
  • (36).Tracey KJ, Wei H, Manogue KR, Fong Y, Hesse D, et al. Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. J Exp Med. 1988;167:1211–1227. doi: 10.1084/jem.167.3.1211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (37).Tracey KJ, Lowry SF, Fahey TJ, Albert JD, Fong Y, Hesse D, et al. Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surg Gynecol Obstet. 1987;164:415–422. [PubMed] [Google Scholar]
  • (38).Beutler B, Krochin N, Milsark IW, Luedke C, Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science. 1986;232:977–980. doi: 10.1126/science.3754653. [DOI] [PubMed] [Google Scholar]
  • (39).Cerami A. Tumor necrosis factor as a mediator of shock, cachexia and inflammation. Blood Purif. 1993;11:108–117. doi: 10.1159/000170104. [DOI] [PubMed] [Google Scholar]
  • (40).Tracey KJ, Fong Y, Hesse DG, Manogue KR, Lee AT, Kuo GC, Lowry SF, Cerami A. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature. 1987;330:662–664. doi: 10.1038/330662a0. [DOI] [PubMed] [Google Scholar]
  • (41).Bone RC. Monoclonal antibodies to tumor necrosis factor in sepsis: help or harm? Crit Care Med. 1993;21:311–312. doi: 10.1097/00003246-199303000-00001. [DOI] [PubMed] [Google Scholar]
  • (42).Rogy MA, Moldawer LL, Oldenburg HSA, Thompson WA, et al. Antiendotoxin therapy in primate bacteremia with HA-1A and BPI. Annals Surg. 1994;220:77–85. doi: 10.1097/00000658-199407000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (43).Waage A, Espevik T. Interleukin 1 potentiates the lethal effect of tumor necrosis factor alpha/cachectin in mice. J Exp Med. 1988;167:1987–1992. doi: 10.1084/jem.167.6.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (44).Rothstein JL, Schreiber H. Synergy between tumor necrosis factor and bacterial products causes hemorrhagic necrosis and lethal shock in normal mice. Proc Natl Acad Sci USA. 1988;85:607–611. doi: 10.1073/pnas.85.2.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (45).Fong Y, Tracey KJ, Moldawer LL, Hesse DG, Manogue KB, Kenney JS, et al. Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 beta and interleukin 6 appearance during lethal bacteremia. J Exp Med. 1989;170:1627–1633. doi: 10.1084/jem.170.5.1627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (46).Ohlsson K, Bjork P, Bergenfeldt M, Hageman R, Thompson RC. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature. 1990;348:550–552. doi: 10.1038/348550a0. [DOI] [PubMed] [Google Scholar]
  • (47).Wakabayashi G, Gelfand JA, Burke JF, Thompson RC, Dinarello CA. A specific receptor antagonist for interleukin 1 prevents Escherichia coli-induced shock in rabbits. FASEB J. 1991;5:338–343. doi: 10.1096/fasebj.5.3.1825816. [DOI] [PubMed] [Google Scholar]
  • (48).Alexander HR, Doherty GM, Venzon DJ, Merino MJ, Fraker DL, Norton JA. Recombinant interleukin-I receptor antagonist (IL-1ra): effective therapy against gram-negative sepsis in rats. Surgery. 1992;112:188–193. [PubMed] [Google Scholar]
  • (49).Fischer E, Marano MA, Van Zee KJ, Rock CS, Hawes AS, Thompson WA, et al. Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coli septic shock, but fails to alter host responses to sublethal endotoxemia. J Clin Invest. 1992;89:1551–1557. doi: 10.1172/JCI115748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (50).Rogy MA, Oldenburg HSA, Coyle S, Trousdale R, Moldawer LL, Lowry SF: Correlation between APACHE III and immunological parameters in critically ill septic patients. Br J Surg (in press). [DOI] [PubMed]
  • (51).Alexander HR, Doherty GM, Venzon DJ, Merino MJ, Fraker DL, Norton JA. Recombinant interleukin-1 receptor antagonist (IL-1ra): effective therapy against gram-negative sepsis in rats. Surgery. 1992;112:188–193. [PubMed] [Google Scholar]
  • (52).Block MI, Berg M, McNamara MJ, Norton JA, Fraker DL, Alexander HR. Passive immunization of mice against D factor blocks lethality and cytokine release during endotoxemia. J Exp Med. 1993;178:1085–1090. doi: 10.1084/jem.178.3.1085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (53).Beutler BA, Milsark IW, Cerami A. Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo. J Immunol. 1985;135:3972–3977. [PubMed] [Google Scholar]
  • (54).Granowitz EV, Vannier E, Poutsiaka DD, Dinarello CA. Effect of interleukin-1 (IL-1) blockade on cytokine synthesis: II. IL-1 receptor antagonist inhibits lipopolysaccharide-induced cytokine synthesis by human monocytes. Blood. 1992;79:2364–2369. [PubMed] [Google Scholar]
  • (55).Fischer E, Van Zee KJ, Marano MA, Rock CS, Kenney JS, et al. Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease. Blood. 1992;79:2196–2200. [PubMed] [Google Scholar]
  • (56).Rogy MA, Coyle SM, Oldenburg HSA, Rock CS, et al. Persistently elevated soluble TNF receptor and interleukin-1 receptor antagonist levels in critically ill patients. J Am Coll Surg. 1994;178:132–138. [PubMed] [Google Scholar]
  • (57).Fisher CJ, Jr, Agosti JM, Opal SM, et al. Treatment of septic shock with the TNF receptor: Fc fusion protein. N Engl J Med. 1996;334:1697–1701. doi: 10.1056/NEJM199606273342603. [DOI] [PubMed] [Google Scholar]
  • (58).Fisher CJ, Jr, Opal SM, Dhainaut JF, Stephens S, Zimmerman JL, et al. Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis. The CBOOO6 Sepsis Syndrome Study Group. Crit Care Med. 1993;21:318–327. doi: 10.1097/00003246-199303000-00006. [DOI] [PubMed] [Google Scholar]
  • (59).Fisher CJ, Jr, Slotman GJ, Opal SM, Pribble JP, Bone RC, et al. Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome. A randomized open-label, placebo-controlled multicenter trial. Crit Care Med. 1994;22:12–21. doi: 10.1097/00003246-199404000-00008. [DOI] [PubMed] [Google Scholar]
  • (60).Echtenacher B, Falk W, Mannel DN, Krammer PH. Requirement of endogenous tumor necrosis factor/cachectin for recovery from experimental peritonitis. J Immunol. 1990;145:3762–3766. [PubMed] [Google Scholar]
  • (61).Czuprynski CJ, Haak Frendscho M, Maroushek N, Brown JF. Effects of recombinant human interleukin-6 alone and in combination with recombinant interleukin-1 alpha and tumor necrosis factor alpha on antibacterial resistance in mice. Antimicrob Agents Chemother. 1992;36:68–70. doi: 10.1128/aac.36.1.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (62).Roll JT, Young KM, Kurtz RS, Czuprynski CJ. Human r TNF alpha augments anti-bacterial resistance in mice: potentiation of its effects by recombinant human rIL-1 alpha. Immunology. 1990;69:316–322. [PMC free article] [PubMed] [Google Scholar]
  • (63).van der Meer JW, Vogels M, Curfs JH, Eling WM. Interleukin-I as a possible agent for treatment of infection. Eur J Clin Microbiol Infect Dis. 1993;12(Suppl 1):S73–S77. doi: 10.1007/BF02389883. [DOI] [PubMed] [Google Scholar]
  • (64).van der Meer JW, Helle M, Aarden L. Comparison of the effects of recombinant interleukin 6 and recombinant interleukin 1 on non-specific resistance to infection. Eur J Immunol. 1989;19:413–416. doi: 10.1002/eji.1830190229. [DOI] [PubMed] [Google Scholar]
  • (65).Perez C, Albert I, DeFay K, Zachariades N, Gooding L, Kriegler MA. Non-secretable cell surface mutant of tumor necrosis factor (TNF) kills by cell-to-cell contact. Cell. 1990;63:251–258. doi: 10.1016/0092-8674(90)90158-B. [DOI] [PubMed] [Google Scholar]
  • (66).Mathison JC, Wolfson E, Ulevitch RJ. Participation of tumor necrosis factor in the mediation of gram negative bacterial lipopolysaccharideinduced injury in rabbits. J Clin Invest. 1988;81:1925–1937. doi: 10.1172/JCI113540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (67).Ginsberg HS, Moldawer LL, Sehgal PB, Redington M, Kilian PL, Chanock RM, Prince GA. A mouse model for investigating the molecular pathogenesis of adenovirus pneumonia. Proc Natl Acad Sci USA. 1991;88:1651–1655. doi: 10.1073/pnas.88.5.1651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (68).Marano MA, Moldawer LL, Fong Y, Wei H, Minei J, Yurt R, Cerami A, Lowry SF. Cachectin/TNF production in experimental burns and pseudomonas infection. Arch Surg. 1988;123:1383–1388. doi: 10.1001/archsurg.1988.01400350097015. [DOI] [PubMed] [Google Scholar]
  • (69).Keogh C, Fong Y, Marano MA, Seniuk S, He W, Barber A, Minei JP, Felsen D, Lowry SF, Moldawer LL. Identification of a novel tumor necrosis factor alpha / cachectin from the livers of burned and infected rats. Arch Surg. 1990;125:79–84. doi: 10.1001/archsurg.1990.01410130085011. [DOI] [PubMed] [Google Scholar]
  • (70).Ulich TR, Guo K, del Castillo J. Endotoxin-induced cytokine gene expression in vivo. Expression of tumor necrosis factor mRNA in visceral organs under physiologic conditions and during endotoxemia. Am J Pathol. 1989;134:11–14. [PMC free article] [PubMed] [Google Scholar]
  • (71).Hyers TM, Tricomi SM, Dettenmeier PA, Fowler AA. Tumor necrosis factor levels in serum and bronchoalveolar lavage fluid of patients with the adult respiratory distress syndrome. Am Rev Respir Dis. 1991;144:268–271. doi: 10.1164/ajrccm/144.2.268. [DOI] [PubMed] [Google Scholar]
  • (72).Suter PM, Suter S, Girardin E, Roux Lombard P, Grau GE, Dayer JM. High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis. Am Rev Respir Dis. 1992;145:1016–1022. doi: 10.1164/ajrccm/145.5.1016. [DOI] [PubMed] [Google Scholar]
  • (73).Ashkenazi A, Marsters SA, Capon DJ, Chamow SM, Figari IS, et al. Protection against endotoxic shock by a tumor necrosis factor receptor immunoadhesin. Proc Natl Acad Sci USA. 1991;88:10535–10539. doi: 10.1073/pnas.88.23.10535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (74).Beutler B, Cerami A. Cachectin and tumour necrosis factor as two sides of the same biological coin. Nature. 1986;320:584–588. doi: 10.1038/320584a0. [DOI] [PubMed] [Google Scholar]
  • (75).Mancilla J, Garcia P, Dinarello CA. The interleukin-1 receptor antagonist can either reduce or enhance the lethality of Klebsiella pneumoniae sepsis in newborn rats. Infect Immun. 1993;61:926–932. doi: 10.1128/iai.61.3.926-932.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (76).Rothe J, Lesslauer W, Lötscher HR, lang Y, Koebel P, et al. Mice lacking the tumor necrosis factor receptor 1 are resistent to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature. 1993;364:798–802. doi: 10.1038/364798a0. [DOI] [PubMed] [Google Scholar]
  • (77).Salmons B, Gunzburg WH. Targeting of retroviral vectors for gene therapy. Hum Gene Ther. 1993;4:129–141. doi: 10.1089/hum.1993.4.2-129. [DOI] [PubMed] [Google Scholar]
  • (78).Roe T, Reynolds TC, Yu G, Brown PO. Integration of murine leukemia virus DNA depends on mitosis. EMBO J. 1993;12:2099–2108. doi: 10.1002/j.1460-2075.1993.tb05858.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (79).Ellison V, Abrams H, Roe T, Lifson J, Brown P. Human immunodeficiency virus integration in a cell-free system. J Virol. 1990;64:2711–2715. doi: 10.1128/jvi.64.6.2711-2715.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (80).Rogy MA, Auffenberg T, Espat NJ, Philip R, Remick D, Wollenberg GK, Copeland EM, Moldawer LL. Human tumor necrosis factor receptor (p55) and interleukin 10 gene transfer in the mouse reduces mortality to lethal endotoxemia and also attenuates local inflammatory responses. J Exp Med. 1995;181:2289–2293. doi: 10.1084/jem.181.6.2289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (81).Hume DM, Benjamin T, Zukoski CF, Lee HM, Kaufmann HM, Egdahl RH. The homotransplantation of kidneys and of fetal liver and spleen after total body irradiation. Annals Surg. 1960;152:354–373. [PMC free article] [PubMed] [Google Scholar]
  • (82).Calne RY. Rejection of renal homografts: inhibition in dogs by 6-mercaptopurine. Lancet. 1960;I:417–417. doi: 10.1016/S0140-6736(60)90343-3. [DOI] [PubMed] [Google Scholar]
  • (83).Calne RY, Rolles K, Thiru S, McMaster P, et al. Cyclosporin A initially as the only immunosuppressant in 34 patients of cadaveric organs: 32 kidneys, 2 pancreas, and 2 livers. Lancet. 1979;II:1033–1036. doi: 10.1016/S0140-6736(79)92440-1. [DOI] [PubMed] [Google Scholar]
  • (84).Starzl TE, Todo S, Fung J, Demetris AJ, Venkataramanan R, Jain A. FK 506 for human liver, kidney and pancreas transplantation. Lancet. 1989;II:1000–1004. doi: 10.1016/S0140-6736(89)91014-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (85).Alonso-Pulpon L, Serrano-Fiz S, Rubio JA, Cavero MA, Silva L, et al. Efficacy of low dose OKT3 as cytolytic induction therapy in heart transplantation. J Heart Lung Transpl. 1995;14:136–142. [PubMed] [Google Scholar]
  • (86).Qin L, Chavin KD, Ding Y, Favaro JP, Woodward JE, et al. Multiple vectors effectively achieve gene transfer in a murine cardiac transplantation model. Transplantation. 1995;59:809–816. doi: 10.1097/00007890-199503270-00002. [DOI] [PubMed] [Google Scholar]
  • (87).Qin L, Chavin KD, Ding Y, Woodward JE, Favaro JP, Lin J, Bromberg JS. Gene transfer for transplantation, prolongation of allograft survival with transforming growth factor-β1. Ann Surg. 1995;220:508–519. doi: 10.1097/00000658-199410000-00009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (88).Larsen CP, Elwood ET, Alexander DZ, Ritchie SC, Hendrix R, et al. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature. 1996;381:434–438. doi: 10.1038/381434a0. [DOI] [PubMed] [Google Scholar]
  • (89).Ding L, Linsley PS, Huang LY, Germain RN, Shevach EM. IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the upregulation of 87 expression. J Immunol. 1993;151:1224–1234. [PubMed] [Google Scholar]

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