Skip to main content

9 Intracellular Single-Chain Antibodies for Gene Therapy

  • Protocol
Gene Therapy of Cancer

Part of the book series: Methods in Molecular Medicineā„¢ ((MIMM,volume 35))

  • 602 Accesses

Abstract

The delineation of the molecular basis of cancer in general, allows for the possibility of specific intervention at the molecular level for therapeutic purposes. To this end, three main approaches have been developed: mutation compensation, molecular chemotherapy, and genetic immunopotentiation. The strategy of mutation compensation aims to correct the specific genetic defects in cancer cells. Such correction is accomplished by either ablation of oncogenic products, replacement of cellular tumor suppressor genes, or interference with dysregulated signal transduction pathways. A second strategy is molecular chemotherapy, which aims to increase the specificity of drug delivery or to increase tolerance to standard chemotherapeutic regimens. A third strategy, genetic immunotherapy, aims to augment the specificity and/or the magnitude of the normal immune response to tumors. For each of these conceptual approaches, human clinical protocols have entered Phase I clinical trials to assess dose escalation, safety, and toxicity issues.

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

Access this chapter

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

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Krol, A.V. and Stuitje, A. R. (1988) Modulation of eukaryotic gene expression by complement RNA or DNA sequences. Biotechniques 6, 958ā€“976.

    PubMedĀ  Google ScholarĀ 

  2. Helene, C. and Toulme, J-J. (1990) Specific regulation of gene expression by antisense, sense, and antigene nucleic acids. Biochem. Biophys. 1049, 99ā€“125.

    CASĀ  Google ScholarĀ 

  3. Gibson, I. (1996) Antisense approaches to the gene therapy of cancer. Cancer Metastasis Rev. 15, 287ā€“299.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  4. Milligan, J. F., Jones, R. J., Froehler, B. C., and Matteucci, M. D. (1994) Development of antisense therapeutics. Implications for cancer gene therapy. Ann. NY Acad. Sci. 716, 228ā€“241.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  5. Stein, C. A. and Cheng, Y-C. (1993) Antisense oligonucleotides as therapeutic agents-is the bullet really magic? Science 261, 1004ā€“1012.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  6. Stein, C. A. (1995) Does antisense exist? Nat. Med. 1, 1119ā€“1121.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  7. Theuer, C. P. and Pastan, I. (1993) Immunotoxins and recombinant toxins in the treatment of solid carcinomas. Amer. J. Surg., 166, 284ā€“288.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  8. Brinkmann, U., Pai, L. H., and FitzGerald, D. J. (1991) B3-(Fv)-PE38KDEL, a single chain immunotoxin that causes complete regression of a human carcinoma in mice. Proc. Natl. Acad. Sci. USA 88, 8616ā€“8620.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  9. Hoogenboom, H. R., Marks, J. D., Griffiths, A. D., and Winter, G. (1992) Building antibodies from their genes. Immunol. Rev. 130, 41ā€“68.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  10. Jost, C. R., Kurucz, I., Jacobus, C. M., Titus, J. A., George, A. J., and Segal, D. M. (1994) Mammalian expression and secretion of functional single-chain Fv molecules. J. Biol. Chem. 269, 26,267ā€“26,273.

    PubMedĀ  CASĀ  Google ScholarĀ 

  11. Richardson, J. H. and Marasco, W. A. (1995) Intracellular antibodies: development and therapeutic potential. Trends Biotech. 13, 306ā€“310.

    ArticleĀ  CASĀ  Google ScholarĀ 

  12. Chen, S. Y., Bagley, J., and Marasco, W. A. (1994) Intracellular antibodies as a new class of therapeutic molecules for gene therapy. Hum. Gene Ther. 5, 595ā€“601.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  13. Colcher, D., Bird, R., and Roselli, M. (1990) In vivo tumor targeting of a recombinant single-chain antigen-binding protein. J. Natl. Can. Inst. 82, 1191ā€“1197.

    ArticleĀ  CASĀ  Google ScholarĀ 

  14. Wawrzynczak, E. J. (1992) Rational design of immunotoxins: current progress and future prospects. Anti-Cancer Drug Design 7, 427ā€“441.

    PubMedĀ  CASĀ  Google ScholarĀ 

  15. Mykebust, A. T., Godal, A., and Fodstad, O. (1994) Targeted therapy with immunotoxins in a nude rat model for leptomenineal growth of human small cell cancer. Cancer Res. 54, 2146ā€“2150.

    Google ScholarĀ 

  16. Marasco, W. A., Haseltine, W. A., and Chen, S-Y. (1993) Design, intracellular expression, and activity of human anti-human immunodeficiency virus type 1 gp120 single-chain antibody. Proc. Natl. Acad. Sci. USA 90, 7889ā€“7893.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  17. Friedman, P. N., Chance, D. F., and Trail, P. A. (1993) Antitumor activity of the single-chain immunotoxin BR96 sFv-PE40 against established breast and lung tumor xenografts. J. Immunol. 150, 3054ā€“3061.

    PubMedĀ  CASĀ  Google ScholarĀ 

  18. Werge, T. M., Biocca, S., and Cattaneo, A. (1990) Cloning andintracellular expression of a monoclonal antibody to the p21ras protein. FEBS Lett. 274, 193ā€“198.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  19. Deshane, J., Loechel, F., Conry, R. M., Siegal, G. P., King, C. R., and Curiel, D. T. (1994) Intracellular single-chain antibody directed against erbB2 down-regulates cell surface erbB2 and exhibits a selective anti-proliferative effect in erbB2 overexpressing cancer cell lines. Gen. Ther. 1, 332ā€“337.

    CASĀ  Google ScholarĀ 

  20. Deshane, J., Siegal, G. P., Alvarez, R. D., Wang, M. H., Feng, M., Cabrera, G., et al. (1995) Targeted tumor killing via an intracellular antibody against erbB-2. J. Clinic. Investigat. 96, 2980ā€“2989.

    ArticleĀ  CASĀ  Google ScholarĀ 

  21. Deshane, J., Grim, J., Loechel, S., Siegal, G. P., Alvarez, R. D., and Curiel, D. T. (1996) Intracellular antibody against erbB-2 mediates targeted tumor cell eradication by apoptosis. Cancer Gene Ther. 3, 89ā€“98.

    PubMedĀ  CASĀ  Google ScholarĀ 

  22. Grim, J., Deshane, J., Feng, M., Lieber, A., Kay, M., and Curiel, D. T. (1996) erbB-2 knockout employing an intracellular single-chain antibody (sFv) accomplishes specific toxicity in erbB-2-expressing lung cancer cells. Amer. J. Respir. CellMolec. Biol. 15, 348ā€“354.

    CASĀ  Google ScholarĀ 

  23. Barnes, D. M., Deshane, J., Siegal, G. P., Alvarez, R. D., and Curiel, D. T. (1996) Novel gene therapy strategy to accomplish growth factor modualtion induces enhanced tumor cell chemosensitivity. Clinic. Cancer Res. 2, 1089ā€“1095.

    CASĀ  Google ScholarĀ 

  24. Wright, M., Grim, J., Kim, M., Strong, T. V., Siegal, G. P., and Curiel, D. T. (1997) An intracellular anti-erbB-2 single-chain antibody is specifically cytotoxic to human breast carcinoma cells overexpressing erbB-2. Gene Ther. 4, 317ā€“322.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  25. Kim, M., Wright, M., Deshane, J., Accavitti, M. A., Tilden, A., Saleh, et al. (1997) A novel gene therapy strategy for elimination of prostate carcinoma cells from human bone marrow. Human Gene Ther. 8, 157ā€“170.

    ArticleĀ  CASĀ  Google ScholarĀ 

  26. Curiel, D. T. Targeted tumor cytotoxicity mediated by intracellular single-chain antioncogene antibodies in Gene Therapy in Advances in pharmacology (Thomas August, J., ed.), Academic, New York, Vol. 40, pp. 51ā€“84.

    Google ScholarĀ 

  27. McCafferty, J., Griffiths, A. D., Winter, G., and Chriswell, D. J. (1990) Phage antibodies: filamentous phage displaying antibody variable domains. Nature 348, 552ā€“554.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  28. Rodenburg, C., Mernaugh, R., Bilbao, G., and Khazaeli M. B. (1998) Production of a single cahin anti-CEA antibody from the hybridoma cell line T84.66 using a modified colony-lift selection procedure to detect antigen-positive scFv bacterial clones. Hybridoma 17, 1ā€“8.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

Ā© 2000 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Bilbao, G., Gomez-Navarro, J., Kazano, K., Luis Contreras, J., Curiel, D.T. (2000). 9 Intracellular Single-Chain Antibodies for Gene Therapy. In: Walther, W., Stein, U. (eds) Gene Therapy of Cancer. Methods in Molecular Medicineā„¢, vol 35. Humana Press. https://doi.org/10.1385/1-59259-086-1:121

Download citation

  • DOI: https://doi.org/10.1385/1-59259-086-1:121

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-714-4

  • Online ISBN: 978-1-59259-086-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics