Abstract
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.
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Acknowledgments
This work was funded by the Intramural Research Program of the National Cancer Institute. TF performed experiments, analyzed data and partially wrote the manuscript; JS performed experiments, analyzed data and partially wrote the manuscript; MM and ST performed experiments and analyzed data; CM provided intellectual and financial support for the experiments shown, analyzed data and partially wrote the manuscript. The authors thank Dr. Martin Guimond for his careful review of this manuscript. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. ST and JK were supported by the Howard Hughes Medical Institute Research Scholars Program.
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Fry, T.J., Shand, J.L., Milliron, M. et al. Antigen loading of DCs with irradiated apoptotic tumor cells induces improved anti-tumor immunity compared to other approaches. Cancer Immunol Immunother 58, 1257–1264 (2009). https://doi.org/10.1007/s00262-008-0638-7
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DOI: https://doi.org/10.1007/s00262-008-0638-7