Induction of anti-tumor immunity by vaccination with dendritic cells pulsed with anti-CD44 IgG opsonized tumor cells

Pilon-Thomas, Shari, Verhaegen, Monique, Kuhn, Lisa, Riker, Adam and Mule, James J. (2006) Induction of anti-tumor immunity by vaccination with dendritic cells pulsed with anti-CD44 IgG opsonized tumor cells. Cancer Immunology Immunotherapy, 55 10: 1238-1246. doi:10.1007/s00262-005-0104-8


Author Pilon-Thomas, Shari
Verhaegen, Monique
Kuhn, Lisa
Riker, Adam
Mule, James J.
Title Induction of anti-tumor immunity by vaccination with dendritic cells pulsed with anti-CD44 IgG opsonized tumor cells
Journal name Cancer Immunology Immunotherapy   Check publisher's open access policy
ISSN 0340-7004
Publication date 2006-10
Sub-type Article (original research)
DOI 10.1007/s00262-005-0104-8
Volume 55
Issue 10
Start page 1238
End page 1246
Total pages 9
Place of publication Germany
Publisher Springer
Language eng
Abstract 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 (Fcγ receptors) that mediate the internalization of antigen-IgG complexes and promote efficient MHC class I and II restricted antigen presentation. In this study, the efficacy 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 GM-CSF 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 efficacy of vaccination with DC+B16-CD44, mice were vaccinated subcutaneously Lymphocytes from mice vaccinated with DC+B16-CD44 produced IFN-γ in response to B16 melanoma lysates as well as an MHC class I restricted B16 melanoma-associated peptide, indicating B16 specific 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 significantly 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 efficacy of targeting tumor antigens to DC via Fcγ receptors.
Keyword Established Pulmonary Metastases
In-Vivo
Antigen Presentation
T-Cells
Recombinant Interleukin-2
Breast-Cancer
Cd44
Maturation
Responses
Melanoma
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
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