hCAR-EGFP fusion receptor in human follicular lymphoma B cells - A model for adenoviral gene therapy for B cell malignancies

  • Authors:
    • Mikko Mättö
    • Ulla-Maija Nuutinen
    • Tanja Hakkarainen
    • Tiziano Tallone
    • Jarmo Wahlfors
    • Jukka Pelkonen
  • View Affiliations

  • Published online on: June 1, 2006     https://doi.org/10.3892/ijmm.17.6.1057
  • Pages: 1057-1062
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Adenovirus-mediated gene therapy for hematopoietic malignancies, especially those derived from B cells, is difficult due to systemic nature of these diseases. More importantly, most tumor cells derived from B cell lineage express a very low level of the adenovirus receptor hCAR; thus, warranting the design of adenoviral vectors with high affinity to abundant B cell surface molecules. To mimic this approach and to test the validity of adenoviral vectors in gene therapy of disseminated malignancies, we created an hCAR-expressing follicular lymphoma B cell line. The cell line was generated with the aid of a lentivirus vector carrying a novel fusion gene with EGFP replacing the cytoplasmic domain of hCAR. After verifying that this cell line was expressing the hybrid receptor in a correct manner and enrichment of the bright EGFP positive population, the cells were transduced with adenoviruses expressing the red fluorescent protein DsRed2. It was shown that regular transduction with a low viral dose (1 pfu/cell) increased the gene transfer rate by a factor of 5. Furthermore, experiments with adenovirus vector carrying the HSV-TK-GFP transgene demonstrated that the modified follicular lymphoma B cells became sensitive to ganciclovir while the parental cells remained virtually resistant to this form of gene therapy. In summary, we show here with this simple model system that adenoviral gene therapy of B cell malignancies is possible provided that correct receptors for adenovirus attachment are present on the surface of the target cells. Thus, our results warrant further modifications of adenovirus capsid to obtain vectors with specific affinity to B cell epitopes.

Related Articles

Journal Cover

June 2006
Volume 17 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Mättö M, Nuutinen U, Hakkarainen T, Tallone T, Wahlfors J and Pelkonen J: hCAR-EGFP fusion receptor in human follicular lymphoma B cells - A model for adenoviral gene therapy for B cell malignancies. Int J Mol Med 17: 1057-1062, 2006
APA
Mättö, M., Nuutinen, U., Hakkarainen, T., Tallone, T., Wahlfors, J., & Pelkonen, J. (2006). hCAR-EGFP fusion receptor in human follicular lymphoma B cells - A model for adenoviral gene therapy for B cell malignancies. International Journal of Molecular Medicine, 17, 1057-1062. https://doi.org/10.3892/ijmm.17.6.1057
MLA
Mättö, M., Nuutinen, U., Hakkarainen, T., Tallone, T., Wahlfors, J., Pelkonen, J."hCAR-EGFP fusion receptor in human follicular lymphoma B cells - A model for adenoviral gene therapy for B cell malignancies". International Journal of Molecular Medicine 17.6 (2006): 1057-1062.
Chicago
Mättö, M., Nuutinen, U., Hakkarainen, T., Tallone, T., Wahlfors, J., Pelkonen, J."hCAR-EGFP fusion receptor in human follicular lymphoma B cells - A model for adenoviral gene therapy for B cell malignancies". International Journal of Molecular Medicine 17, no. 6 (2006): 1057-1062. https://doi.org/10.3892/ijmm.17.6.1057