Antibody-mediated FOXP3 protein therapy induces apoptosis in cancer cells in vitro and inhibits metastasis in vivo

  • Authors:
    • Emil Heinze
    • Scott Baldwin
    • Grace Chan
    • James Hansen
    • Jason Song
    • Douglas Clements
    • Robert Aragon
    • Robert Nishimura
    • Mark Reeves
    • Richard Weisbart
  • View Affiliations

  • Published online on: July 1, 2009     https://doi.org/10.3892/ijo_00000325
  • Pages: 167-173
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Abstract

In addition to its immune suppressive function in T-regulatory cells, the nuclear transcription factor, FOXP3, has been identified as a tumor suppressor. To evaluate the clinical efficacy of monoclonal antibody (mAb) 3E10 Fv antibody-mediated FOXP3 protein therapy of cancer, the Fv-FOXP3 fusion protein produced in Pichia pastoris was tested on breast, ovarian, and colon cancer cells in vitro, and with colon cancer cells in vivo in a mouse model of colon cancer metastasis to liver. Treatment with Fv-FOXP3 resulted in dose-dependent cell death of cancer cells in vitro. Apoptosis was established as a mechanism of cell death by demonstrating increased production of the p17 activated fragment of caspase-3 by cancer cells in response to Fv-FOXP3 and inhibition of cell killing by the caspase inhibitor, Z-VAD-FMK. Fv-FOXP3 treatment resulted in clinically significant reduction in tumor burden in a syngeneic model of colon cancer metastasis to liver in Balb/c mice. These results represent the first demonstration of effective full-length FOXP3 protein therapy and emphasize the clinical potential of mAb 3E10 as an intracellular and intranuclear delivery vehicle of FOXP3 for prevention and treatment of cancer metastasis.

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July 2009
Volume 35 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Heinze E, Baldwin S, Chan G, Hansen J, Song J, Clements D, Aragon R, Nishimura R, Reeves M, Weisbart R, Weisbart R, et al: Antibody-mediated FOXP3 protein therapy induces apoptosis in cancer cells in vitro and inhibits metastasis in vivo. Int J Oncol 35: 167-173, 2009
APA
Heinze, E., Baldwin, S., Chan, G., Hansen, J., Song, J., Clements, D. ... Weisbart, R. (2009). Antibody-mediated FOXP3 protein therapy induces apoptosis in cancer cells in vitro and inhibits metastasis in vivo. International Journal of Oncology, 35, 167-173. https://doi.org/10.3892/ijo_00000325
MLA
Heinze, E., Baldwin, S., Chan, G., Hansen, J., Song, J., Clements, D., Aragon, R., Nishimura, R., Reeves, M., Weisbart, R."Antibody-mediated FOXP3 protein therapy induces apoptosis in cancer cells in vitro and inhibits metastasis in vivo". International Journal of Oncology 35.1 (2009): 167-173.
Chicago
Heinze, E., Baldwin, S., Chan, G., Hansen, J., Song, J., Clements, D., Aragon, R., Nishimura, R., Reeves, M., Weisbart, R."Antibody-mediated FOXP3 protein therapy induces apoptosis in cancer cells in vitro and inhibits metastasis in vivo". International Journal of Oncology 35, no. 1 (2009): 167-173. https://doi.org/10.3892/ijo_00000325