1. ¹Department of Dermatology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
2. ²Department of Stem Cell Transplantation and Cell Therapy, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
3. ³Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

Correspondence: Dr Xiao Ni, Department of Dermatology, The University of Texas, MD Anderson Cancer Center, Box 434, 1515 Holcombe Blvd, Houston, Texas 77030, USA. E-mail: xiaoni@mdanderson.org

Received 11 October 2007; Revised 2 February 2008; Accepted 19 March 2008; Published online 15 May 2008.

Abstract

Sézary syndrome (SzS), the leukemic variant of cutaneous T-cell lymphomas, is incurable. Dendritic cells (DCs) transfected with tumor mRNA can stimulate antitumor immunity in certain cancer patients. In this study, we determined whether mRNAs from Sézary cells could be used for loading DCs and stimulating antitumor immunity. Autologous DCs were generated from monocytes of the peripheral blood from 10 patients with SzS. Total RNA was extracted from Sézary cells and amplified by T7 in vitro transcription. The induction of antitumor IFN- and granzyme B (GrB)-producing cytotoxic T lymphocytes (CTL) by RNA-transfected DCs was determined by ELISPOT assays. We found that IFN- was required for IL-12p70 production by monocyte-derived DCs from SzS. The oncogenic transcription factor Twist and the tyrosine kinase receptor EphA4 were expressed in total RNA from Sézary cells and the paired amplified mRNAs. RNA-transfected DCs induced antitumor IFN--producing CTLs in 7 of 10 subjects and GrB-producing CTLs in 6 of 9 subjects. Both CD3+CD8+ T cells and CD4+CD25+ T cells were expanded without induction of regulatory T cells. These data support the concept of using tumor mRNA for a vaccine strategy that requires small amounts of tumor cells without need for specific antigens in patients with SzS.