PMID- 19139888 OWN - NLM STAT- MEDLINE DCOM- 20090612 LR - 20211028 IS - 1432-0851 (Electronic) IS - 0340-7004 (Print) IS - 0340-7004 (Linking) VI - 58 IP - 8 DP - 2009 Aug TI - Antigen loading of DCs with irradiated apoptotic tumor cells induces improved anti-tumor immunity compared to other approaches. PG - 1257-64 LID - 10.1007/s00262-008-0638-7 [doi] AB - 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. FAU - Fry, Terry J AU - Fry TJ AD - Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, MD 20892, USA. fryt@mail.nih.gov FAU - Shand, Jessica L AU - Shand JL FAU - Milliron, Matthew AU - Milliron M FAU - Tasian, Sarah K AU - Tasian SK FAU - Mackall, Crystal L AU - Mackall CL LA - eng GR - T32 HD044331/HD/NICHD NIH HHS/United States GR - Z99 CA999999/ImNIH/Intramural NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20090113 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 RN - 0 (Cancer Vaccines) RN - 0 (H-Y Antigen) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Animals MH - *Antigen Presentation MH - Apoptosis MH - CD4-Positive T-Lymphocytes/immunology/metabolism MH - CD8-Positive T-Lymphocytes/immunology/metabolism MH - Cancer Vaccines/*immunology/therapeutic use MH - Carcinoma/*immunology/therapy MH - Cell Line, Tumor MH - Dendritic Cells/*immunology/transplantation MH - Female MH - H-Y Antigen/*immunology MH - *Immunotherapy, Adoptive MH - Interleukin-12/immunology/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Urinary Bladder Neoplasms/*immunology/therapy PMC - PMC2791794 MID - NIHMS161683 EDAT- 2009/01/14 09:00 MHDA- 2009/06/13 09:00 PMCR- 2009/01/13 CRDT- 2009/01/14 09:00 PHST- 2008/05/22 00:00 [received] PHST- 2008/12/01 00:00 [accepted] PHST- 2009/01/14 09:00 [entrez] PHST- 2009/01/14 09:00 [pubmed] PHST- 2009/06/13 09:00 [medline] PHST- 2009/01/13 00:00 [pmc-release] AID - 638 [pii] AID - 10.1007/s00262-008-0638-7 [doi] PST - ppublish SO - Cancer Immunol Immunother. 2009 Aug;58(8):1257-64. doi: 10.1007/s00262-008-0638-7. Epub 2009 Jan 13.