[HTML][HTML] Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells

J Dannull, Z Su, D Rizzieri, BK Yang… - The Journal of …, 2005 - Am Soc Clin Investig
J Dannull, Z Su, D Rizzieri, BK Yang, D Coleman, D Yancey, A Zhang, P Dahm, N Chao…
The Journal of clinical investigation, 2005Am Soc Clin Investig
In this study, we investigated whether elimination of CD4+/CD25+ Tregs using the
recombinant IL-2 diphtheria toxin conjugate DAB389IL-2 (also known as denileukin diftitox
and ONTAK) is capable of enhancing the immunostimulatory efficacy of tumor RNA-
transfected DC vaccines. We show that DAB389IL-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. DAB389IL-2–mediated Treg …
In this study, we investigated whether elimination of CD4+/CD25+ Tregs using the recombinant IL-2 diphtheria toxin conjugate DAB389IL-2 (also known as denileukin diftitox and ONTAK) is capable of enhancing the immunostimulatory efficacy of tumor RNA-transfected DC vaccines. We show that DAB389IL-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. DAB389IL-2–mediated Treg depletion resulted in enhanced stimulation of proliferative and cytotoxic T cell responses in vitro but only when DAB389IL-2 was omitted during T cell priming. DAB389IL-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, DAB389IL-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.
The Journal of Clinical Investigation