Skip to main content
SpringerLink
Log in

Gene Therapy With Immunotoxins

  • Protocol
Immunotoxin Methods and Protocols

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 166))

  • 410 Accesses

Abstract

The purpose of this chapter is to describe the method of treating lymphokine-activated killer (LAK) cells with retroviral immunotoxins (retIT) so that these cells can express and secrete immunotoxins (IT). The intent is to use LAK as a vehicle to deliver IT therapy directly to leukemia cells in vivo. This would reduce their systemic toxicity and thus solve a major problem that has limited the use of IT clinically.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
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
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover 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

References

  1. Jain, R. K. (1989) Delivery of novel therapeutic agents in tumors: physiological barriers and strategies. J. Natl. Cancer Inst. 81, 570–576.

    Article  PubMed  CAS  Google Scholar 

  2. Shockley, T. R., Lin, K., Sun,g C., Nagy, J. A., Tompkins, R. G., Derick, R. L., et al. (1992) A quantitative analysis of tumor-specific monoclonal antibody uptake by human melanoma xenografts: effects of antibody immunological properties and tumor antigen expression levels. Cancer Res. 52, 357–366.

    PubMed  CAS  Google Scholar 

  3. Sung C., Shockley T. R., Morrison P. F., Dvorak H. F., Yarmush, M. L., and Dedrick, R. L. (1992) Predicted and observed effects of antibody affinity and antigen density on monoclonal antibody uptake in solid tumors. Cancer Res. 52, 377–384.

    PubMed  CAS  Google Scholar 

  4. Baxter, L. T., Yuan, F., and Jain, R. K. (1992) Pharmacokinetic analysis of the perivascular distribution of bifunctional antibodies and haptens: comparison with experimental data. Cancer Res. 52, 5838–5844.

    PubMed  CAS  Google Scholar 

  5. Rosenberg, S. A., Packard, B. S., Aebersold, P. M., Solomon, D., Topalian, S. L., Toy, S. T., et al. (1988) Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. N. Engl. J. Med. 319, 1676–1680.

    Article  PubMed  CAS  Google Scholar 

  6. Frankel A., ed. (1992) Genetically Engineered Toxins. Marcel Dekker Inc., New York, pp. 3–115.

    Google Scholar 

  7. Honjo, T., Nishizuka, Y., Hataishi, O., and Kato, I. (1968) Diphtheria toxindependent adenosine diphosphate ribosylation of aminoacyl transferase II and inhibition of protein synthesis. J. Biol. Chem. 243, 3553–55.

    PubMed  CAS  Google Scholar 

  8. Collier, R. J. (1975) Diphtheria toxin: mode of action and structure. Bact. Rev. 39, 54–85.

    PubMed  CAS  Google Scholar 

  9. Vallera, D.A. (1994) Immunotoxins: will their clinical promise be fulfilled? Blood 83, 309–17.

    PubMed  CAS  Google Scholar 

  10. Foss, F. M., Borkowski, T. A., Gilliom, M., Stetler-Stevenson, M., Jaffe, E. S., Figg, W. D., et al. (1994) Chimeric fusion protein toxin DAB486IL-2 in advanced mycosis fungoides and the Sezary syndorme: correlation of activity and interleukin-2 receptor expression in a phase II study. Blood 84, 1765–1774.

    PubMed  CAS  Google Scholar 

  11. Lindauer, M., Stinisslawski, T., Haussler, A., Antunes, E., Huber, C., and Theobald, M. (1998) The molecular basis of cancer immunotherapy by cytotoxic T lymphocytes J. Mol. Med. 76, 32–47.

    Article  PubMed  CAS  Google Scholar 

  12. Matsumura, T., Sussman, J. J., Krinock, R. A., Chang, A. E., and Shu, S. (1994) Characteristics and in vivo homing of long-term T-cell lines and clones derived from tumor-draining lymph nodes. Cancer Res. 54, 2744–2750.

    PubMed  CAS  Google Scholar 

  13. Bolhuis, R. L. H., Strum, E., and Braakman, E. (1991) T-cell targeting in cancer therapy. Cancer Immunol. Immunother. 34, 1–8

    Article  PubMed  CAS  Google Scholar 

  14. Eshhar, Z., Waks, T., Gross, G., and Schindler, D. (1993) Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc. Natl. Acad. Sci. USA 90, 720–724

    Article  PubMed  CAS  Google Scholar 

  15. Gross, G., Waks, T., and Eshhar, Z. (1989) Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc. Natl. Acad. Sci. USA 86, 10,024–10,028.

    Article  PubMed  CAS  Google Scholar 

  16. Topalian, S., Solomon, D., and Rosenberg, S. A. (1989) Tumor specific cytolysis by lymphocytes infiltrating human melanomas. J. Immunol. 142, 3714–3725.

    PubMed  CAS  Google Scholar 

  17. Chen, S-Y., Yang, A-G., Chen, J-D., Kute, T., King, R., Collers, J., et al. (1997) Potent antitumour activity of a new class of tumour-specific killer cells. Nature 385, 78–80.

    Article  PubMed  CAS  Google Scholar 

  18. Yang, A. G. and Chen, S.-Y. (1997) A new class of antigen-specific killer cells. Nat. Biotechnol. 15, 46–51.

    Article  PubMed  CAS  Google Scholar 

  19. Rapoport, T. A., Rolls, M., and Jungnickel, B. (1996) Approaching the mechanism of protein transport across the ER membrane. Curr. Op. Cell Biol. 8, 499–504.

    Article  PubMed  CAS  Google Scholar 

  20. Walter, P. and Johnson, A. E. (1994) Signal sequence recognition and protein targeting to the endoplasmic reticulum membrane. Annu. Rev. Cell Biol. 10, 87–119.

    Article  PubMed  CAS  Google Scholar 

  21. Parker, S., Tong, T., Bolden, S., and Wingo, P. (1997) Cancer statistics. CA Cancer J. Clin. 47, 5–12.

    Article  PubMed  CAS  Google Scholar 

  22. Schiffer C. (1997) Acute myeloid leukemia in adults, in Cancer Medicine (Holland, J., Frei, E., Bast, R., Kufe, D., and Marton, D., eds.), Weichselbaum R. Lea, and Febiger, Philadelphia, pp. 2617–2633.

    Google Scholar 

  23. Durham, L. J. and Stewart, H. L. (1953) A survey of transplantable and transmissible animal tumors. J. Natl. Canc. Inst. 13, 1299–1377.

    Google Scholar 

  24. Bradner, W. T. and Pindell, M. H. (1966) Myeloid leukemia C1498 as a screen for cancer chemotherapeutic agents. Cancer Res. Cancer 43, 375–390.

    Google Scholar 

  25. Chesebro, B., Britt, W., Evans, K., Wehrly, K., Nishio, J., and Cloyd, M. (1983) Characterization of monoclonal antibodies reactive with murine leukemia viruses. Virology 127, 134–148.

    Article  PubMed  CAS  Google Scholar 

  26. Wagteveld, A. J., van Zanten, A. K., Esselink, M. T., Halie, M. R., and Vellenga, E. (1991) Expression and regulation of IL-4 receptors on human monocytes and acute myeloblastic leukemic cells. Leukemia 5, 782–788.

    PubMed  CAS  Google Scholar 

  27. Ohara, J. and Paul, W. E. (1988) Up-regulation of interleukin 4/B-cell stimulatory factor 1 receptor expression. Proc. Natl. Acad. Sci. USA 85, 8221–8227.

    Article  PubMed  CAS  Google Scholar 

  28. Lowenthal, J. W., Castle, B. E., Christian, J., Schreurs, J., Rennick, D., Arai, N., et al. (1988) Expression of high affinity receptors for murine interleukin-4 (BSF-1) on hematopoietic and nonhematopoietic cells. J. Immunol. 140, 456–464.

    PubMed  CAS  Google Scholar 

  29. Debinski, W., Puri, R. K., Kreitman, R. J., and Pastan, I. (1993) A wide range of human cancers express interleukin 4 (IL-4) receptors that can be targeted with chimeric toxin composed of IL-4 and Pseudomonas exotoxin. J. Biol. Chem. 268, 14,065–14,070.

    PubMed  CAS  Google Scholar 

  30. Puri, R. K., Hoon, D. S., Lelan, P., Snoy, P., Rand, R. W., Pastan, I., et al. (1996) Preclinical development of a recombinant toxin containing circularly permuted interleukin 4 and truncated Pseudomonas exotoxin for therapy of malignant astrocytoma. Cancer Res. 56, 5631–5637.

    PubMed  CAS  Google Scholar 

  31. Buchsbaum D. J., Laffoon K. Rogers, B. E., Curiel D. T., Khazaeli M. B., McLean, S., et al. (1997) Radiolabeled DT390-mIL-4 fusion toxin binding and cytotoxicity to tumor cell induced to express mIL-4 receptor. Cancer Gene Ther. 4, S41.

    Google Scholar 

  32. Boyer, M. W., Vallera, D. A., Taylor, P. A., Gray, G. S., Katsanis, E., Gorden, K., et al. (1997) The role of B7.1 by murine acute myeloid leukemia cells in the generation and function of a CD8+ T cell line with potent in vivo graft-versus-leukemia (GVL) properties. Blood 89, 3477–3454.

    Google Scholar 

  33. Vallera D. A., Jin N., Baldrica J., Panoskaltsis-Mortari A., Chen S.-Y., and Blazar BR. (2000). Retroviral immunotoxin gene therapy of acute myelogenous leukemia (AML) in mice using cytotoxic T cells (CTL) transduced with an IL-4/diphtheria toxin gene. Cancer Res. 60, 976–984.

    PubMed  CAS  Google Scholar 

  34. Chen, J. D., Bai, X., Yang, A. G., Cong, Y., and Chen, S. Y. (1997) Inactivation of HIV-1 chemokine co-receptor CXCR-4 by a novel intrakine strategy. Nat. Med. 10, 1074, 1075.

    Google Scholar 

  35. Matzinger P. (1991) The JAM test: a simple assay for DNA fragmentation and cell death. J. Immunol. Methods 145, 185–192.

    Article  PubMed  CAS  Google Scholar 

  36. Chan, C. H., Blazar, B. R., Eide, C. R., Greenfield, L., Krietman,R. J., and Vallera, D. A. (1996) Reactivity of murine cytokine fusion toxin, DT390-mIL-3, with bone marrow progenitor cells. Blood 88, 1445–1451.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Minnesota Cancer Center, Department of Therapeutic Radiology, University of Minnesota, Minneapolis, MN

    Daniel A. Vallera

Authors
  1. Daniel A. Vallera
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota

    Walter A. Hall MD

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Vallera, D.A. (2001). Gene Therapy With Immunotoxins. In: Hall, W.A. (eds) Immunotoxin Methods and Protocols. Methods in Molecular Biology™, vol 166. Humana Press. https://doi.org/10.1385/1-59259-114-0:235

Download citation

  • DOI: https://doi.org/10.1385/1-59259-114-0:235

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-775-5

  • Online ISBN: 978-1-59259-114-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation