Induction of anti-tumor immunity by vaccination with dendritic cells pulsed with anti-CD44 IgG opsonized tumor cells.
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 (Fcgamma 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-gamma 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 Fcgamma receptors.
Pilon-Thomas
Shari
S
H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., SRB-3 Room 23244, Tampa, FL 33612, USA. pilontsa@moffitt.usf.edu
Verhaegen
Monique
M
Kuhn
Lisa
L
Riker
Adam
A
Mulé
James J
JJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D018960:Hyaluronan Receptors / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL
D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D018960:Hyaluronan Receptors; D007074:Immunoglobulin G