Rettig, L; Seidenberg, S; Parvanova, I; Samaras, P; Knuth, A; Pascolo, S (2011). Gemcitabine depletes regulatory T-cells in human and mice and enhances triggering of vaccine-specific cytotoxic T-cells. International Journal of Cancer, 129(4):832-.838.
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Particle Mediated Epidermal Delivery (PMED) is a potent genetic vaccination method. However, a recent report found PMED only poorly and infrequently triggered antigen-specific cytotoxic T-cells in cancer patients. Here, we show that injection of the chemotherapeutic drug Gemcitabine in mice results in improvement of the efficacy of subsequent PMED vaccination against NY-ESO-1. We found in mice and in cancer patients that administration of Gemcitabine induces a transient reduction in the percentage of regulatory T-cells among CD4-positive cells. The higher relative sensitivity of regulatory T-cells compared with other CD4-positive T-cells towards cytostatic drugs can be linked to the higher frequency of proliferating cells in the regulatory compartment compared with the non-regulatory CD4-compartment in healthy people and cancer patients. Thus, by affecting regulatory T-cells more than other lymphocyte subsets, chemotherapeutic agents can create a transient hyper-immunoreactive window. Such a window would provide an ideal timepoint to administer a vaccine expected to induce a therapeutically relevant anti-cancer cytotoxic T-cell response.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology|
|Dewey Decimal Classification:||610 Medicine & health|
|Deposited On:||19 Jan 2011 11:56|
|Last Modified:||27 Nov 2013 17:09|
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