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Liposome-mediated gene transfer into human basal cell carcinoma

Gene Therapy volume 6, pages 1929–1935 (1999)Cite this article

Abstract

Direct intralesional injection of DNA encoding interferon-α2 (IFN-α2) was used in an effort to sustain local protein delivery for the treatment of human basal cell carcinoma (BCC). A novel model to study this malignancy was established by transplantation of human BCC tissue on to immunodeficient mice with a relatively high rate of engraftment and stable phenotype for superficial BCC (20 of 25; 80%). Gene transfer was significantly increased by using DNA liposome complexes (lipoplexes). Recombinant gene expression was detected predominantly in the epidermis and, to a lesser extent, in the dermis. Gene transfer of IFN-α2 using this method resulted in sustained production of IFN-α2 protein and increased expression of a known IFN-inducible gene, the class II major histocompatibility (MHC) antigen, and induced BCC regression, presumably through a non-immune mechanism. Intralesional injection of DNA lipoplexes encoding IFN-α protein may therefore be applicable to the treatment of cutaneous BCC.

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References

  1. Miller DL, Weinstock MA . Nonmelanoma skin cancer in the United States: incidence J Am Acad Dermatol 1999 30: 774–778

    Article  Google Scholar 

  2. Buechner SA . Intralesional interferon alfa-2b in the treatment of basal cell carcinoma: immunohistochemical study on cellular immune reaction leading to tumor regression J Am Acad Dermatol 1991 24: 731–734

    Article  CAS  Google Scholar 

  3. Cornell RC et al. Intralesional interferon therapy for basal cell carcinoma J Am Acad Dermatol 1990 23: 694–700

    Article  CAS  Google Scholar 

  4. Greenway HT et al. Treatment of basal cell carcinoma with intralesional interferon J Am Acad Dermatol 1986 15: 437–443

    Article  CAS  Google Scholar 

  5. Grob JJ, Collet AM, Munoz MH, Bonerandi JJ . Treatment of large basal-cell carcinomas with intralesional interferon-alpha-2a Lancet 1988 1: 878–879

    Article  CAS  Google Scholar 

  6. Hunt MJ et al. Regression in basal cell carcinoma: an immunohistochemical analysis Br J Dermatol 1994 130: 1–8

    Article  CAS  Google Scholar 

  7. Thestrup-Pedersen K, Jacobsen IE, Frentz G . Intralesional interferon-alpha 2b treatment of basal cell carcinoma Acta Derm Venereol 1990 70: 512–514

    CAS  PubMed  Google Scholar 

  8. Wickramasinghe L, Hindson TC, Wacks H . Treatment of neoplastic skin lesions with intralesional interferon J Am Acad Dermatol 1989 20: 71–74

    Article  CAS  Google Scholar 

  9. Chimenti S et al. Use of recombinant interferon alfa-2b in the treatment of basal cell carcinoma Dermatology 1995 190: 214–217

    Article  CAS  Google Scholar 

  10. Dellon AL, Elfenbein GJ, Orlando JC . Impairment of thymus-derived lymphoid cell function in patients with basal cell carcinoma J Surg Oncol 1984 25: 92–97

    Article  CAS  Google Scholar 

  11. Murphy GF, Krusinski PA, Myzak LA, Ershler WB . Local immune response in basal cell carcinoma: characterization by transmission electron microscopy and monoclonal anti-T6 antibody J Am Acad Dermatol 1983 8: 477–485

    Article  CAS  Google Scholar 

  12. Myskowski PL, Safai B, Good RA . Decreased lymphocyte blastogenic responses in patients with multiple basal cell carcinoma J Am Acad Dermatol 1981 4: 711–714

    Article  CAS  Google Scholar 

  13. Meissner K et al. Quantitative analysis of T6-positive Langerhans cells in human skin cancers Virchows Arch 1986 410: 57–63

    Article  CAS  Google Scholar 

  14. Knop J . Immunologic effects of interferon J Invest Dermatol 1990 95: 72S–74S

    Article  CAS  Google Scholar 

  15. Mozzanica N et al. Immunohistological evaluation of basal cell carcinoma immunoinfiltrate during intralesional treatment with alpha 2-interferon Arch Dermatol Res 1990 282: 311–317

    Article  CAS  Google Scholar 

  16. Buechner SA et al. Regression of basal cell carcinoma by intralesional interferon-alpha treatment is mediated by CD95 (Apo-1/Fas)-CD95 ligand-induced suicide J Clin Invest 1997 100: 2691–2696

    Article  CAS  Google Scholar 

  17. Nabel GJ et al. Immune response in human melanoma after transfer of an allogeneic class I major histocompatibility complex gene with DNA–liposome complexes Proc Natl Acad Sci USA 1996 93: 15388–15393

    Article  CAS  Google Scholar 

  18. Nabel GJ et al. Direct gene transfer with DNA–liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans Proc Natl Acad Sci USA 1993 90: 11307–11311

    Article  CAS  Google Scholar 

  19. Nabel GJ et al. Direct gene transfer for treatment of human cancer. In: Liu MA, Hilleman MR, Kurth R (eds) . DNA Vaccines: A New Era in Vaccinology New York Academy of Sciences: New York 1995 227–231

    Google Scholar 

  20. Stephan DJ et al. A new cationic liposome DNA complex enhances the efficiency of arterial gene transfer in vivo Hum Gene Ther 1996 7: 1803–1812

    Article  CAS  Google Scholar 

  21. Pawlowski A, Haberman HF . Heterotransplantation of human basal cell carcinomas in ‘nude’ mice J Invest Dermatol 1979 72: 310–313

    Article  CAS  Google Scholar 

  22. Grimwood RE et al. Transplantation of human basal cell carcinomas to athymic mice Cancer 1985 56: 519–523

    Article  CAS  Google Scholar 

  23. Grimwood RE, Tharp MD . Growth of human basal cell carcinomas transplanted to C57/Balb/C bgJbgJ-nu/nu (beige-nude) mice J Dermatol Surg Oncol 1991 17: 661–666

    Article  CAS  Google Scholar 

  24. Gutterman JU . Cytokine therapeutics: lessons from interferon alpha Proc Natl Acad Sci USA 1994 91: 1198–1205

    Article  CAS  Google Scholar 

  25. Pestka S, Langer JA, Zoon KC, Samuel CE . Interferons and their actions Annu Rev Biochem 1987 56: 727–777

    Article  CAS  Google Scholar 

  26. Pfeffer LM et al. Biological properties of recombinant alpha-interferons: 40th anniversary of the discovery of interferons Cancer Res 1998 58: 2489–2499

    CAS  Google Scholar 

  27. Horton HM et al. A gene therapy for cancer using i.m. injection of plasmid DNA encoding interferon-a Proc Natl Acad Sci USA 1999 96: 1553–1558

    Article  CAS  Google Scholar 

  28. San H et al. Safety and short-term toxicity of a novel cationic lipid formulation for human gene therapy Hum Gene Ther 1993 4: 781–788

    Article  CAS  Google Scholar 

  29. Sambrook J, Fritch EF, Maniatis T . Molecular Cloning: A Laboratory Manual Cold Spring Laboratory Harbor Press: Cold Spring Harbor, NY 1989

    Google Scholar 

  30. Leung K, Nabel GJ . HTLV-I transactivator induces interleukin-2 receptor expression through an NF-kB-like factor Nature 1988 333: 776–778

    Article  CAS  Google Scholar 

  31. Manthorpe M et al. Gene therapy by intramuscular injection of plasmid DNA: studies on firefly luciferase gene expression in mice Hum Gene Ther 1993 4: 419–431

    Article  CAS  Google Scholar 

  32. Michael G . Nitroblue tetrazolium chloride (NBT). In: Bergmeyer V (ed) . Methods of Enzymatic Analysis, 3rd edn Academic Press: New York 1983 197–232

    Google Scholar 

  33. Yokota T, Reeves AG, MacLean PD . Intracellular olfactory response of hippocampal neurons in awake, sitting squirrel monkeys Science 1967 157: 1072–1074

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Ms Nancy Barrett and Ms Donna Gschwend for manuscript preparation and other members of the Nabel laboratory for their helpful advice and comments, and Jon Norman and colleagues at Vical for kindly providing DMRIE/DOPE. MOH is supported by the Commission for the Advancement of Young Scientists and Scholars of the University of Zurich, Switzerland. This work was supported in part by a grant from the National Institutes of Health (1 P01 CA59327).

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Author notes

  1. M O Hottiger and T N Dam: The first two authors contributed equally to this work

Authors and Affiliations

  1. Departments of Internal Medicine and Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI, USA

    M O Hottiger & G J Nabel

  2. Department of Dermatology, Otorhinolaryngology, and Surgery, The University of Michigan Medical Center, Ann Arbor, MI, USA

    T N Dam & T M Johnson

  3. Department of Pathology, Loyola University Medical Center, Skin Cancer Research Laboratories, Cardinal Bernardin Cancer Center, Maywood, IL, USA

    B J Nickoloff

  4. Institute of Veterinary Biochemistry, The University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland

    M O Hottiger

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Hottiger, M., Dam, T., Nickoloff, B. et al. Liposome-mediated gene transfer into human basal cell carcinoma. Gene Ther 6, 1929–1935 (1999). https://doi.org/10.1038/sj.gt.3301036

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