PMID- 15922965 OWN - NLM STAT- MEDLINE DCOM- 20051006 LR - 20210102 IS - 1525-0016 (Print) IS - 1525-0016 (Linking) VI - 11 IP - 6 DP - 2005 Jun TI - Enhanced immunity by NeuEDhsp70 DNA vaccine Is needed to combat an aggressive spontaneous metastatic breast cancer. PG - 941-9 AB - The rapid growth and ruthless metastasis of tumors demand effective broad immune responses. Dendritic cells (DCs) are critical in developing tumor vaccines. Recent investigations have been focused on modifying tumor antigens to target DCs to induce immune responses efficiently in vivo. In this study, human hsp70 was fused to the extracellular domain of rat Her2/Neu (NeuEDhsp70) for enhancing anti-tumor immunity in aggressive breast tumor models. NeuEDhsp70-conditioned DCs produced significant IL-12p40 and effectively presented NeuED antigens to T cells in vitro. NeuEDhsp70 DNA vaccine induced enhanced Neu-specific antibody and IFN-gamma-producing cellular immune responses in vivo. Although NeuEDhsp70 and NeuED DNA vaccines elicited comparable therapeutic anti-tumor immunity in an aggressive primary breast tumor model, NeuEDhsp70 DNA vaccine significantly increased survival and reduced metastasis in an aggressive spontaneous metastatic breast tumor model. Results from animal experiments with depletion of immune cells or with deficiency of CD40 molecules indicate that T cells and CD40 molecules are critical in the anti-tumor immunity induced by NeuEDhsp70 DNA vaccine. These observations suggest that NeuEDhsp70 DNA vaccine is a promising reagent to induce potent anti-tumor immunity to an aggressive spontaneous metastatic breast tumor. FAU - Kim, Jin H AU - Kim JH AD - Department of Dermatology and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. FAU - Majumder, Nilanjana AU - Majumder N FAU - Lin, Honghui AU - Lin H FAU - Chen, Janet AU - Chen J FAU - Falo, Louis D Jr AU - Falo LD Jr FAU - You, Zhaoyang AU - You Z LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Ther JT - Molecular therapy : the journal of the American Society of Gene Therapy JID - 100890581 RN - 0 (Antigens, Neoplasm) RN - 0 (CD40 Antigens) RN - 0 (Cancer Vaccines) RN - 0 (Interleukin-12 Subunit p40) RN - 0 (NeuEDhsp70 fusion protein, recombinant) RN - 0 (Protein Subunits) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Vaccines, DNA) RN - 187348-17-0 (Interleukin-12) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Animals MH - Antigens, Neoplasm/immunology MH - Bone Marrow Neoplasms/*prevention & control/secondary MH - CD4-Positive T-Lymphocytes/immunology MH - CD40 Antigens/analysis MH - Cancer Vaccines/genetics/*immunology/*therapeutic use MH - Dendritic Cells/immunology MH - Female MH - Interleukin-12/analysis MH - Interleukin-12 Subunit p40 MH - Mammary Neoplasms, Animal/*drug therapy/immunology/pathology MH - Mice MH - Protein Subunits/analysis MH - Rats MH - Receptor, ErbB-2/immunology MH - Recombinant Fusion Proteins/genetics/*immunology MH - Vaccines, DNA/immunology/therapeutic use EDAT- 2005/06/01 09:00 MHDA- 2005/10/07 09:00 CRDT- 2005/06/01 09:00 PHST- 2004/08/06 00:00 [received] PHST- 2004/12/27 00:00 [revised] PHST- 2005/01/05 00:00 [accepted] PHST- 2005/06/01 09:00 [pubmed] PHST- 2005/10/07 09:00 [medline] PHST- 2005/06/01 09:00 [entrez] AID - S1525-0016(05)00005-5 [pii] AID - 10.1016/j.ymthe.2005.01.003 [doi] PST - ppublish SO - Mol Ther. 2005 Jun;11(6):941-9. doi: 10.1016/j.ymthe.2005.01.003.