PMID- 16844231 OWN - NLM STAT- MEDLINE DCOM- 20061031 LR - 20231213 IS - 0165-2478 (Print) IS - 0165-2478 (Linking) VI - 106 IP - 2 DP - 2006 Aug 15 TI - Enhancement of dendritic cell-based vaccine potency by targeting antigen to endosomal/lysosomal compartments. PG - 126-34 AB - Dendritic cells (DCs) are the central players in cancer immunotherapy because of their distinct ability to prime immune responses. In previous work with DNA vaccines, we described an intracellular targeting approach that routed a nuclear/cytoplasmic antigen, human papillomavirus (HPV) type 16 E7, into the endosomal and lysosomal compartments. It does so by linking E7 with the sorting signal of lysosome-associated membrane protein 1 (Sig/LAMP-1) to enhance the presentation of E7 antigen to MHC class I-restricted CD8(+) T cells, as well as to MHC class II-restricted CD4(+) T cells. To date, the Sig/LAMP-1 targeting strategy has not been tested in the context of DC-based vaccines. This study was designed to determine whether targeting HPV-16 E7 to the endosomal/lysosomal compartment can enhance the potency of DC vaccines. In immunological studies, DC-Sig/E7/LAMP-1 dramatically increased in vitro activation and in vivo expansion of E7-specific CD4(+) and CD8(+) T cells, compared with DC-E7 and DC-No insert. More importantly, in both tumor prevention and tumor treatment assays, DC-Sig/E7/LAMP-1 generated greater anti-tumor immunity against TC-1 than DC-E7. Our results demonstrate that linkage of the antigen gene to an endosomal/lysosomal targeting signal may greatly enhance the potency of DC-based vaccines. FAU - Kang, Tae Heung AU - Kang TH AD - Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, 516 Gojan-1 Dong, Ansan-Si, Gyeonggi-Do 425-707, South Korea. FAU - Lee, Jin Hyup AU - Lee JH FAU - Bae, Hyun Cheol AU - Bae HC FAU - Noh, Kyung Hee AU - Noh KH FAU - Kim, Jin Hee AU - Kim JH FAU - Song, Chung Kil AU - Song CK FAU - Shin, Byung Chul AU - Shin BC FAU - Hung, Chien-Fu AU - Hung CF FAU - Wu, T-C AU - Wu TC FAU - Park, Jong-Sup AU - Park JS FAU - Kim, Tae Woo AU - Kim TW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060522 PL - Netherlands TA - Immunol Lett JT - Immunology letters JID - 7910006 RN - 0 (Cancer Vaccines) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Lamp1 protein, mouse) RN - 0 (Lysosomal Membrane Proteins) RN - 0 (Oncogene Proteins, Viral) RN - 0 (Papillomavirus E7 Proteins) RN - 0 (Protein Sorting Signals) RN - 0 (oncogene protein E7, Human papillomavirus type 16) SB - IM MH - Animals MH - Antigen Presentation/genetics/immunology MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - Cancer Vaccines/genetics/*immunology MH - Dendritic Cells/*immunology/transplantation MH - Endosomes/genetics/*immunology MH - Female MH - Histocompatibility Antigens Class II/immunology MH - Lymphocyte Activation/genetics/immunology MH - Lysosomal Membrane Proteins/genetics/immunology MH - Lysosomes/genetics/*immunology MH - Mice MH - Neoplasms, Experimental/genetics/*immunology MH - Oncogene Proteins, Viral/genetics/*immunology MH - Papillomavirus E7 Proteins MH - Protein Sorting Signals/genetics EDAT- 2006/07/18 09:00 MHDA- 2006/11/01 09:00 CRDT- 2006/07/18 09:00 PHST- 2005/12/13 00:00 [received] PHST- 2006/04/17 00:00 [revised] PHST- 2006/05/01 00:00 [accepted] PHST- 2006/07/18 09:00 [pubmed] PHST- 2006/11/01 09:00 [medline] PHST- 2006/07/18 09:00 [entrez] AID - S0165-2478(06)00130-1 [pii] AID - 10.1016/j.imlet.2006.05.004 [doi] PST - ppublish SO - Immunol Lett. 2006 Aug 15;106(2):126-34. doi: 10.1016/j.imlet.2006.05.004. Epub 2006 May 22.