Journal of Leukocyte Biology Accuri Cytometers
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on July 1, 2008

Published online before print April 21, 2008
This Article
Right arrow Full Text (Reprint (PDF))
Right arrow HTML Page - index.htslp
Right arrow All Versions of this Article:
jlb.1107737v1
84/1/319    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, J.-J.
Right arrow Articles by Kalinski, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, J.-J.
Right arrow Articles by Kalinski, P.
© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1107737

Received for publication November 8, 2007.
Revised March 13, 2008.
Accepted for publication March 13, 2008.

Article

Type 1-polarized dendritic cells loaded with autologous tumor are a potent immunogen against chronic lymphocytic leukemia

Je-Jung Lee , Kenneth A. Foon , Robbie B. Mailliard , Ravikumar Muthuswamy , and Pawel Kalinski @

Departments of Surgery and Medicine, University of Pittsburgh, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA

@ To whom correspondence should be addressed. E-mail: kalinskip{at}upmc.edu.


  Abstract

Induction of active tumor-specific immunity in patients with chronic lymphocytic leukemia (CLL) and other hematologic malignancies is compromised by the deficit of endogenous dendritic cells (DCs). In attempt to develop improved vaccination strategies for patients with CLL and other tumors with poorly identified rejection antigens, we tested the ability of ex vivo-generated DCs to cross-present the antigens expressed by CLL cells and to induce CLL-specific, functional CTL responses. Monocyte-derived DCs from CLL patients were induced to mature using a "standard" cytokine cocktail (in IL-1{beta}, TNF-{alpha}, IL-6, and PGE2) or using an {alpha}-type 1-polarized DC ({alpha}DC1) cocktail (in IL-1{beta}, TNF-{alpha}, IFN-{alpha}, IFN-{gamma}, and polyinosinic:polycytidylic acid) and were loaded with {gamma}-irradiated, autologous CLL cells. {alpha}DC1 from CLL patients expressed substantially higher levels of multiple costimulatory molecules (CD83, CD86, CD80, CD11c, and CD40) than standard DCs (sDCs) and immature DCs, and their expression of CCR7 showed intermediate level. {alpha}DC1 secreted substantially higher (10–60 times) levels of IL-12p70 than sDCs. Although {alpha}DC1 and sDCs showed similar uptake of CLL cells, {alpha}DC1 induced much higher numbers (range, 2.4–38 times) of functional CD8+ T cells against CLL cells. The current demonstration that autologous tumor-loaded {alpha}DC1 are potent inducers of CLL-specific T cells helps to develop improved immunotherapies of CLL.

Key Words: CLL • vaccines • IL-12 • CTLs






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2008 by the Society for Leukocyte Biology.