Medical Oncology

, Volume 12, Issue 3, pp 143–147 | Cite as

Gene therapy of cancer

  • Arthur Bank


There are several approaches to the gene therapy of cancer. Genes can be introduced into cancer cells to either sensitize them for killing by subsequent treatment with drugs, or to normalize their growth. In addition, genes can be added to tumor cells to provoke an accentuated immune response against these cells leading to cancer cell death. Alternatively, drug resistance genes can be added to bone marrow cells which make these cells more resistant to the toxic effects of chemotherapy, and thus allow higher doses of these drugs to be given without myelotoxicity and with potentially greater tumor kill. Although gene therapy of cancer is at an early stage of development, some of these strategies are being used in approved clinical trials in cancer patients.


gene therapy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cone, R. and Mulligan, R.C. (1984) High-efficiency gene transfer into mammalian cells: Generation of helper-free recombinant retrovirus with broad mammalian host range.Proc. Natl. Acad. Sci. 81, 6349–53.PubMedCrossRefGoogle Scholar
  2. 2.
    Miller, A. (1990) Progress toward human gene therapy.Blood 76, 271–8.PubMedGoogle Scholar
  3. 3.
    Bank, A., Ward, M., Richardson, C., Podda, S., Smith, L. and Hesdorffer, C. (1995) Retroviral gene transfer into hematopoietic stem cells: The human MDR gene as a model system. In D. Levitt and R. Mertlesmann (eds)Hematopoietic stem cells. pp. 229–43. New York: Marcel Dekker.Google Scholar
  4. 4.
    Donahue, R.E., Kessler, S.W., Bodine, D., McDonagh, K., Dunbar, C., Goodman, S., Agricola, B., Byrne, E., Raffeld, M., Moen, al. (1992) Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer.J. Exp. Med. 176.Google Scholar
  5. 5.
    Markowitz, D., Goff, S. and Bank, A. (1988) A safe packaging line for gene transfer: Separating viral genes on two different plasmids.J. Virol. 62, 1120–5.PubMedGoogle Scholar
  6. 6.
    Markowitz, D., Goff, S. and Bank, A. (1988) Construction and use of a safe and efficient amphotropic packaging cell line.Virology 167, 400–5.PubMedGoogle Scholar
  7. 7.
    Culver, K.W. and Blaese, R.M. (1994) Gene therapy for cancer. [Review].Trends in Genetics,10, 174–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Rosenberg, S.A., Anderson, W.F., Blaese, M., Hwu, P., Yannelli, J.R., Yang, J.C., Topalian, S.L., Schwartzentruber, D.J., Weber, J.S., Ettinghausen, al. (1993) The development of gene therapy for the treatment of cancer.Ann. Surgery,218, 455–63; discussion 463–4.CrossRefGoogle Scholar
  9. 9.
    Pardoll, D.M. (1993) Genetically engineered tumor vaccines.Ann. N.Y. Acad. Sci. 690, 301–10.PubMedCrossRefGoogle Scholar
  10. 10.
    Gansbacher, H., Zier, K., Cronin, al. (1992) Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-gamma in irradiated human melanoma cells.Blood 80, 2817–25.PubMedGoogle Scholar
  11. 11.
    Surbone, A. and DeVita, V.T. Jr. (1993) Dose intensity. The neglected variable in clinical trials.Ann. N.Y. Acad. Sci. 698, 279–88.PubMedCrossRefGoogle Scholar
  12. 12.
    Pastan I. and Gottesman, M.M. (1991) Multidrug resistance.Ann. Rev. Med. 42, 277–86.PubMedCrossRefGoogle Scholar
  13. 13.
    Podda, S., Ward, M., Himelstein, A., Richardson, C., de la Flor-Weiss, E., Smith, L., Gottesman, M., Pastan, I. and Bank, A. (1992) Transfer and expression of the human multiple drug resistance gene into live mice.Proc. Natl. Acad. Sci. 89, 9676–80.PubMedCrossRefGoogle Scholar
  14. 14.
    Sorrentino, B.P., Brandt, S.J., Bodino, G., Gottesman, M., Pastan, I., Cline, A. and Nienhuis, A.W. (1992) Selection of drug-resistant bone marrow cells in vivo after retroviral transfer of human MDR1.Science 257, 99–103.PubMedCrossRefGoogle Scholar
  15. 15.
    Richardson, C., Ward, M., Podda, S. and Bank, A. (1994) Mouse fetal liver cells lack functional amphotropic retroviral receptors.Blood 84, 433–9.PubMedGoogle Scholar
  16. 16.
    Richardson, C. and Bank, A. (1995) Preselection of transduced murine hematopoietic stem cell populations leads to increased long-term stability and expression of the human multiple drug resistance gene.Blood 86, 2579–89.PubMedGoogle Scholar
  17. 17.
    Ward, M., Richardson, C., Pioli, P., Ayello, J., Reiss, R, Hesdorffer, C. and Bank, A. (1994) MDR gene transfer and expression into peripheral blood progenitor cells.Blood Suppl.84, 356a.Google Scholar
  18. 18.
    Ward, M., Richardson, C., Pioli, P., Smith, L., Podda, S., Goff, S., Hesdorffer, C. and Bank. A. (1994) Transfer and Expression of the Human Multiple Drug Resistance Gene in Human CD34+ Cells.Blood 84, 1408–14.PubMedGoogle Scholar
  19. 19.
    Hesdorffer, C. and Antman, K. (1994) Clinical Protocol: Human MDR Gene Transfer in Patients with Advanced Cancer.Human Gene Therapy 5, 1151–60.PubMedCrossRefGoogle Scholar
  20. 20.
    Li, M.X., Banerjee, D., Zhao, S.C., Schweitzer, B.I., Mineishi, S., Gilboa, E. and Bertino, J.R. (1994) Development of a retroviral construct containing a human mutated dihydrofolate reductase cDNA for hematopoietic stem cell transduction.Blood 83, 3403–8.PubMedGoogle Scholar
  21. 21.
    Allay, J.A., Dumenco, L.L., Koc, O.N., Liu, L. and Gerson, S.L. (1995) Retroviral transduction and expression of the human alkyltransferase cDNA provides nitrosourea resistance to hematopoietic cells.Blood 85, 3342–51.PubMedGoogle Scholar
  22. 22.
    Magni, M., Shammah, S., Schiro, R., Bregni, M., Siena, S., DiNocola, M., Dalla-Favera, R. and Gianni, A.M. (1994)Blood Suppl,84, 357a.Google Scholar
  23. 23.
    Cole, S.P., Bhardwaj, G., Gerlach, J.H., Mackie, J.E., Grant, C.E., Almquist, K.C., Stewart, A.J., Kurz, E.U., Duncan, A.M. and Deeley, R.G. (1992) Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line.Science 258, 1650–4.PubMedCrossRefGoogle Scholar
  24. 24.
    Cole, S.P., Sparks, K.E., Fraser, K., Loe, D.W., Grant, C.E., Wilson, G.M. and Deeley, R.G. (1994) Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells.Cancer Res. 54, 5902–10.PubMedGoogle Scholar
  25. 25.
    Grant, C.E., Valdimarsson, G., Hipfner, D.R., Almquist, K.C., Cole, S.P. and Deeley, R.G. (1994) Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs.Cancer Res. 54, 357–61.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 1995

Authors and Affiliations

  • Arthur Bank
    • 1
  1. 1.Departments of Medicine, and Genetics and DevelopmentColumbia University College of Physicians and SurgeonsNew YorkUSA

Personalised recommendations