Antigen loading of DCs with irradiated apoptotic tumor cells induces improved anti-tumor immunity compared to other approaches.
Dendritic cells (DCs) serve as central regulators of adaptive immunity by presenting antigens and providing necessary co-signals. Environmental information received by the DCs determines the co-signals delivered to the responding adaptive cells and, ultimately, the outcome of the interaction. DCs loaded with relevant antigens have been used as therapeutic cellular vaccines, but the optimal antigen loading method has not been determined. We compared different methods to load class I and class II epitopes from the male antigenic complex, HY, onto DCs for the potency of the immune response induced in vivo. Co-incubation of female DCs with HY peptides, RNA or cell lysate from HY expressing tumor induced immune responses equivalent to male DCs. In contrast, female DCs incubated with irradiated, apoptotic HY expressing tumor cells (or male B cells) generated a stronger immune response than male DCs or female DCs loaded using any of the other methods. DC loading with apoptotic tumor resulted in complete protection against high dose HY-expressing tumor challenge whereas 100% lethality was observed in groups receiving DCs that were loaded with peptides, RNA, or lysate. We conclude that signals provided to the DCs by apoptotic cells substantially augment the potency of DC vaccines.
Fry
Terry J
TJ
Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD 20892, USA. fryt@mail.nih.gov
Shand
Jessica L
JL
Milliron
Matthew
M
Tasian
Sarah K
SK
Mackall
Crystal L
CL
D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D002277:Carcinoma / Q000276:immunology* / Q000628:therapy; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D006182:H-Y Antigen / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000628:therapy
D019496:Cancer Vaccines; D006182:H-Y Antigen; D018664:Interleukin-12