The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells
Open accessAbstract
In this study, we investigated whether elimination of CD4+/CD25+ Tregs using the recombinant IL-2 diphtheria toxin conjugate DAB(389)IL-2 (also known as denileukin diftitox and ONTAK) is capable of enhancing the immunostimulatory efficacy of tumor RNA-transfected DC vaccines. We show that DAB(389)IL-2 is capable of selectively eliminating CD25-expressing Tregs from the PBMCs of cancer patients without inducing toxicity on other cellular subsets with intermediate or low expression of CD25. DAB(389)IL-2-mediated Treg depletion resulted in enhanced stimulation of proliferative and cytotoxic T cell responses in vitro but only when DAB(389)IL-2 was omitted during T cell priming. DAB(389)IL-2 significantly reduced the number of Tregs present in the peripheral blood of metastatic renal cell carcinoma (RCC) patients and abrogated Treg-mediated immunosuppressive activity in vivo. Moreover, DAB(389)IL-2-mediated elimination of Tregs followed by vaccination with RNA-transfected DCs significantly improved the stimulation of tumor-specific T cell responses in RCC patients when compared with vaccination alone. Our findings may have implications in the design of immune-based strategies that may incorporate the Treg depletion strategy to achieve potent antitumor immunity with therapeutic impact.
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Curiel, T. J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., Evdemon-Hogan, M., Conejo-Garcia, J. R., Zhang, L., Burow, M., et al. (2004) · Nature Medicine · doi:10.1038/nm1093 · Cited by 5,151
Shimizu, J., Yamazaki, S., & Sakaguchi, S. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.10.5211 · Cited by 1,491
Sutmuller, R. P. M., van Duivenvoorde, L. M., van Elsas, A., Schumacher, T. N. M., Wildenberg, M. E., Allison, J. P., Toes, R. E. M., Offringa, R., & Melief, C. J. M. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.6.823 · Cited by 1,008
Su, Z., Dannull, J., Yang, B. K., Dahm, P., Coleman, D., Yancey, D., Sichi, S., Niedzwiecki, D., Boczkowski, D., Gilboa, E., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3798 · Cited by 359
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Cited by
Regulatory T cells in tumor immunity
Nishikawa, H., & Sakaguchi, S. (2010) · International Journal of Cancer · doi:10.1002/ijc.25429 · Cited by 944
Maj, T., Wang, W., Crespo, J., Zhang, H., Wang, W., Wei, S., Zhao, L., Vatan, L., Shao, I., Szeliga, W., et al. (2017) · Nature Immunology · doi:10.1038/ni.3868 · Cited by 733
Interleukin-12: Biological Properties and Clinical Application
Del Vecchio, M., Bajetta, E., Canova, S., Lotze, M. T., Wesa, A., Parmiani, G., & Anichini, A. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0776 · Cited by 601
CD8 + T‐cell memory in tumor immunology and immunotherapy
Klebanoff, C. A., Gattinoni, L., & Restifo, N. P. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00391.x · Cited by 511
Finke, J. H., Rini, B., Ireland, J., Rayman, P., Richmond, A., Golshayan, A., Wood, L., Elson, P., Garcia, J., Dreicer, R., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-5212 · Cited by 492
Metadata
- Authors
- Dannull, J.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-12-01
- Volume
- 115
- Issue
- 12
- Pages
- 3623-3633
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2138163780
- Cited by
- 989
- References
- 4
- FWCI
- 35.95
- Type
- journal article
- Language
- en
- Open access
- bronze
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