Skip to main content
SpringerLink
Log in

Applications of Gene Transfer in Hematologic Malignancy

  • Conference paper
Advances in Hematopoietic Stem Cell Transplantation and Molecular Therapy

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 144))

Abstract

Although gene transfer was originally conceived as a means to replace or correct defective genes in patients with inherited disorders, the process has shown broad potential for intervention in hematologic malignancy and for study of hematopoietic stem cell biology.

Gene transfer strategies now under investigation for these applications include

  1. 1)

    repair of one or more genetic defects associated with the malignant process,

  2. 2)

    delivery of a prodrug-metabolizing enzyme that causes tumor cells to become sensitive to the corresponding anticancer drug,

  3. 3)

    modification of immune responses to the cancer, and

  4. 4)

    introduction of drug resistance genes to increase the therapeutic index of cytotoxic agents.

Finally, by marking normal or malignant cells with readily detectable genes, one can monitor the efficacy of therapy or study the dynamics of stem cell behavior in vivo.

At present these applications are limited by the quality of vectors, but as transduction efficiencies and gene regulatory mechanisms improve, gene transfer can be expected to evolve into a major therapeutic modality in its own right.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Anderson WF (1990) The ADA human gene therapy clinical protocol. Hum Gene Ther 1:327–362

    Article  Google Scholar 

  • Brenner MK, Heslop HE (1991) Graft-versus-host reactions and bone marrow transplantation. Curr Opin Immunol 3:752–757

    Article  CAS  PubMed  Google Scholar 

  • Brenner MK, Rill DR, Moen RC et al (1993) Gene-marking to trace origin of relapse after autologous bone marrow transplantation. Lancet 341:85–86

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Ashe S, Brady WA et al (1992) Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD 28 and CTLA-4. Cell 71:1093–1102

    Article  CAS  PubMed  Google Scholar 

  • Colombo MP, Forni G (1994) Cytokine gene transfer in tumor inhibition and tumor therapy: where are we now? Immunol Today 15:48–51

    Article  CAS  PubMed  Google Scholar 

  • Colombo MP, Ferrari G, Stoppacciaro A et al (1991) Granulocyte colony-stimulating factor gene transfer suppresses tumorogenicity of a murine adenocarcinoma in vivo. J Exp Med 173:889–897

    Article  CAS  PubMed  Google Scholar 

  • Deisseroth AB, Zu Z, Claxton D et al (1994) Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow transplantation in CML. Blood 83:3068–3076

    CAS  PubMed  Google Scholar 

  • Dilloo D, Bacon K, Holden W et al (1997) Chemokine and cytokine gene transfer enhances antitumor immunity. Nature Med (in press)

    Google Scholar 

  • Fearon ER, Pardoe DM, Itaya T et al (1990) Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 60:397–403

    Article  CAS  PubMed  Google Scholar 

  • Fujiwara T, Grimm EA, Cai DW, Owen-Schaub LB, Roth JA (1993) A retroviral wild-type p53 expression vector penetrates human lung cancer spheroids and inhibits growth by inducing apoptosis. Cancer Res 53:4129–4133

    CAS  PubMed  Google Scholar 

  • Gansbacher B, Zier K, Daniels B, Cronin K, Bannerji R, Gilboa E (1990) Interleukin-2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J Exp Med 172:1217–1224

    Article  CAS  PubMed  Google Scholar 

  • Golumbek PT, Lazenby AJ, Levitsky HI et al (1991) Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4. Science 254:713–716

    Article  CAS  PubMed  Google Scholar 

  • Horowitz MM, Gale RP, Sondel PM et al (1990) Graft-versus-leukemia reactions after bone marrow transplantation. Blood 75:555–562

    CAS  PubMed  Google Scholar 

  • Knox RJ, Friedlos F, Boland MP (1993) The bioactivation of CB 1954 and its use as a prodrug in antibody-directed enzyme prodrug therapy (ADEPT). Cancer Metastasis Rev 12:195–212

    Article  CAS  PubMed  Google Scholar 

  • Levin L, Hryniuk WM (1987) Dose intensity analysis of chemotherapy regimens in ovarian carcinoma. J Clin Oncol 5:756

    CAS  PubMed  Google Scholar 

  • McLachlin JR, Eglitis MA, Ueda K et al (1990) Expression of a human complementary DNA for the multidrug resistance gene in murine hematopoietic precursor cells with the use of retroviral gene transfer. J Natl Cancer Inst 82:1260

    Article  CAS  PubMed  Google Scholar 

  • Melief CJ, Kast WM (1993) Potential immunogenicity of oncogene and tumor suppressor gene products. Curr Opin Immunol 5:709–713

    Article  CAS  PubMed  Google Scholar 

  • Mickisch GH, Licht T, Merlino GT, Gottesman MM, Pastan I (1991a) Chemotherapy and chemosensitization of transgenic mice which express the human multidrug resistance gene in bone marrow: efficacy, potency, and toxicity. Cancer Res 51:5417

    CAS  PubMed  Google Scholar 

  • Mickisch GH, Merlino GT, Galski H, Gottesman MM, Pastan I (1991b) Transgenic mice that express the human multidrug-resistance gene in bone marrow enable a rapid identification of agents that reverse drug resistance. Proc Natl Acad Sci USA 88:547

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Moritz T, Mackay W, Feng LJ, Samson L, Williams DA (1993) Gene transfer of O6-methylguanine methyltransferase (MGMT) protects hematopoietic cells (HC) from nitrosourea (NU)-induced toxicity in vitro and in vivo (Abstr). Blood 82 Suppl 1:118a

    Google Scholar 

  • Murphy D, Crowther D, Renninson J et al (1993) A randomised does intensity study in ovarian carcinoma comparing chemotherapy given at four week intervals for six cycles with half dose chemotherapy given for twelve cycles. Ann Oncol 4:377

    CAS  PubMed  Google Scholar 

  • Nabel GJ, Nabel EG, Yang ZY et al (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(23):11307–11311

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Papadopoulos EB, Ladanyi M, Emanuel D et al (1994) Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation. N Engl J Med 330:1185–1191

    Article  CAS  PubMed  Google Scholar 

  • Pastan I, Gottesman MM (1991) Multidrug resistance. Annu Rev Med 42:277

    Article  CAS  PubMed  Google Scholar 

  • Ram Z, Culver KW, Walbridge S et al (1993) In situ retroviral-mediated gene transfer for the treatment of brain tumors in rats. Cancer Res 83–88

    Google Scholar 

  • Ratajczak MZ, Kant JA, Luger SM et al (1992) In vivo treatment of human leukemia in a SCID mouse model with c-myb antisense oligodeoxynucleotides. Proc Natl Acad Sci USA 89:11823–11827

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rill DR, Santana VM, Roberts WM et al (1994) Direct demonstration that autologous bone marrow transplantation for solid tumors can return a multiplicity of tumorigenic cells. Blood 84:380–383

    CAS  PubMed  Google Scholar 

  • Rooney CM, Smith CA, Ng C et al (1995) Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr virus-related lymphoproliferation. Lancet 345:9–13

    Article  CAS  PubMed  Google Scholar 

  • Rosenberg SA (1992) Gene therapy for cancer. JAMA 268:2416–2419

    Article  CAS  PubMed  Google Scholar 

  • Rossi JJ (1995) Therapeutic antisense and ribozymes. Br Med Bull 51:217–225

    CAS  PubMed  Google Scholar 

  • Scanlon KJ, Jiao L, Funato T et al (1991) Ribozyme-mediated cleavage of c-fos mRNA reduces gene expression of DNA synthesis enzymes and metallothionein. Proc Natl Acad Sci USA 88:10591–10595

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Snyder DS, Wu Y, Wang JL et al (1993) Ribozyme-mediated inhibition of bcr-abl gene expression in Philadelphia chromosome-positive cell line. Blood 82:600–605

    CAS  PubMed  Google Scholar 

  • Tepper RI, Pattengale PK, Leder P (1989) Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell 57:503–512

    Article  CAS  PubMed  Google Scholar 

  • Townsend SE, Allison JP (1993) Tumor rejection after direct costimulation of CD 8+ T cells by B 7-transfected melanoma cells. Science 259:368–370

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Bucana CD, Roth JA, Zhang W (1995) Apoptosis induced in human osteosarcoma cells is one of the mechanisms for the cytocidal effect of Ad5CMV-p53. Cancer Gene Ther 2:9–18

    CAS  PubMed  Google Scholar 

  • Wei MX, Tamiya T, Chase M et al (1994) Experimental tumor therapy in mice using the cyclophosphamide-activating cytochrome P450 2 B 1 gene. Hum Gene Ther 5:969–978

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Mukhopadhyay T, Donehower LA, Georges RN, Roth JA (1993) Retroviral vectormediated transduction of K-ras antisense RNA into human lung cancer cells inhibits expression of the malignant phenotype. Hum Gene Ther 4:451–460

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cell and Gene Therapy Program, St. Jude Children’s Research Hospital, 332 N. Lauderdale, Memphis, TN, 38105, USA

    M. K. Brenner

Authors
  1. M. K. Brenner
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer-Verlag Berlin · Heidelberg

About this paper

Cite this paper

Brenner, M.K. (1998). Applications of Gene Transfer in Hematologic Malignancy. In: Advances in Hematopoietic Stem Cell Transplantation and Molecular Therapy. Recent Results in Cancer Research, vol 144. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-46836-0_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-46836-0_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-46838-4

  • Online ISBN: 978-3-642-46836-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation