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Cancer Immunol Immunother (2006) 55: 12381246
DOI 10.1007/s00262-005-0104-8ORIGINAL ARTICLEShari Pilon-Thomas Monique Verhaegen Lisa Kuhn
Adam Riker James J MuleInduction of anti-tumor immunity by vaccination with dendritic cells
pulsed with anti-CD44 IgG opsonized tumor cellsReceived: 7 October 2005 / Accepted: 8 November 2005 / Published online: 29 November 2005
Springer-Verlag 2005Abstract Due to the pivotal role that dendritic cells (DC)
play in eliciting and maintaining functional anti-tumor T
cell responses, these APC have been exploited against
tumors. DC express several receptors for the Fc portion
of IgG (Fcc receptors) that mediate the internalization
of antigen-IgG complexes and promote ecient MHC
class I and II restricted antigen presentation. In this
study, the ecacy of vaccination with DC pulsed with
apoptotic B16 melanoma cells opsonized with an anti-
CD44 IgG (B16-CD44) was explored. Immature bone
marrow derived DC grown in vitro with IL-4 and GMCSF were pulsed with B16-CD44. After 48 h of pulsing,
maturation of DC was demonstrated by production of
IL-12 and upregulation of CD80 and CD40 expression.
To test the ecacy of vaccination with DC+B16-CD44,
mice were vaccinated subcutaneously Lymphocytes
from mice vaccinated with DC+B16-CD44 produced
IFN-c in response to B16 melanoma lysates as well as an
MHC class I restricted B16 melanoma-associated peptide, indicating B16 specic CD8 T cell activation. Upon
challenge with viable B16 cells, all mice vaccinated with
DC alone developed tumor compared to 40% of mice
vaccinated with DC+B16-CD44; 60% of the latter mice
remained tumor free for at least 8 months. In addition,
established lung tumors and distant metastases were
signicantly reduced in mice treated with DC+B16-
CD44. Lastly, delayed growth of established subcutaneous tumors was induced by combination therapy with
anti-CD44 antibodies followed by DC injection.This study demonstrates the ecacy of targeting tumor
antigens to DC via Fcc receptors.IntroductionThe frequency of precursor T cells with anti-tumor
activity is low in patients with advanced cancers. It is
therefore important to activate and expand tumor
reactive T-cells as an eective means of immunity.
Dendritic cells (DC) are known as the most potent
antigen-presenting cells, capable of initiating both primary and memory T cell immune responses and have
become an integral player in immunotherapeutic approaches for the treatment of cancer [13].DC loaded with tumor antigens induce T cell responses capable of overcoming...