PMID- 15887013 OWN - NLM STAT- MEDLINE DCOM- 20060623 LR - 20240427 IS - 0340-7004 (Print) IS - 1432-0851 (Electronic) IS - 0340-7004 (Linking) VI - 55 IP - 3 DP - 2006 Mar TI - Chaperone-rich cell lysates, immune activation and tumor vaccination. PG - 329-38 AB - We have utilized a free-solution-isoelectric focusing technique (FS-IEF) to obtain chaperone-rich cell lysates (CRCL) fractions from clarified tumor homogenates. The FS-IEF technique for enriching multiple chaperones from tumor lysate is relatively easy and rapid, yielding sufficient immunogenic material for clinical use. We have shown that tumor-derived CRCL carry antigenic peptides. Dendritic cells (DCs) uptake CRCL and cross-present the chaperoned peptides to T cells. Tumor-derived CRCL induce protective immune responses against a diverse range of murine tumor types in different genetic backgrounds. When compared to purified heat shock protein 70 (HSP70), single antigenic peptide or unfractionated lysate, CRCL have superior ability to activate/mature DCs and are able to induce potent, long lasting and tumor specific T-cell-mediated immunity. While CRCL vaccines were effective as stand-alone therapies, the enhanced immunogenicity arising from CRCL-pulsed DC as a vaccine indicates that CRCL could be the antigen source of choice for DC-based anti-cancer immunotherapies. The nature of CRCL's enhanced immunogenicity may lie in the broader antigenic peptide repertoire as well as the superior immune activation capacity of CRCL. Exongenous CRCL also supply danger signals in the context of apoptotic tumor cells and enhance the immunogenicity of apoptotic tumor cells, leading to tumor-specific T cell dependent long-term immunity. Moreover, CRCL based vaccines can be effectively combined with chemotherapy to treat cancer. Our findings indicate that CRCL have prominent adjuvant effects and are effective sources of tumor antigens for pulsing DCs. Tumor-derived CRCL are promising anti-cancer vaccines that warrant clinical research and development. FAU - Zeng, Yi AU - Zeng Y AD - Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona, 1501 N. Campbell Ave., PO Box 245073, Tucson, AZ 85724-5073, USA. FAU - Graner, Michael W AU - Graner MW FAU - Katsanis, Emmanuel AU - Katsanis E LA - eng GR - R01 CA104926/CA/NCI NIH HHS/United States GR - R21 CA102410/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20050511 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (Heat-Shock Proteins) SB - IM MH - Animals MH - Antigen Presentation/immunology MH - Antigens, Neoplasm/*immunology MH - Cancer Vaccines/*immunology MH - Dendritic Cells/immunology MH - Heat-Shock Proteins/*immunology MH - Humans MH - Lymphocyte Activation/*immunology MH - Neoplasms/immunology PMC - PMC11030847 EDAT- 2005/05/12 09:00 MHDA- 2006/06/24 09:00 PMCR- 2005/05/11 CRDT- 2005/05/12 09:00 PHST- 2004/10/29 00:00 [received] PHST- 2005/02/21 00:00 [accepted] PHST- 2005/05/12 09:00 [pubmed] PHST- 2006/06/24 09:00 [medline] PHST- 2005/05/12 09:00 [entrez] PHST- 2005/05/11 00:00 [pmc-release] AID - 694 [pii] AID - 10.1007/s00262-005-0694-1 [doi] PST - ppublish SO - Cancer Immunol Immunother. 2006 Mar;55(3):329-38. doi: 10.1007/s00262-005-0694-1. Epub 2005 May 11.