PMID- 18388923 OWN - NLM STAT- MEDLINE DCOM- 20080819 LR - 20171116 IS - 1525-0024 (Electronic) IS - 1525-0016 (Linking) VI - 16 IP - 5 DP - 2008 May TI - Administering plasmid DNA encoding tumor vessel-anchored IFN-alpha for localizing gene product within or into tumors. PG - 901-6 LID - 10.1038/mt.2008.40 [doi] AB - Tumor-targeted gene delivery has been intensively studied in the field of gene therapy, but no attention has been given to targeting the therapeutic gene products, which are transcribed and translated from the injected genes, into tumors. Targeting immune stimulatory gene products into tumors is the key to triggering tumor-specific CD8(+) T-cell responses and reducing systemic toxicity. To target the gene products generated from the injected genes into tumors, genes encoding the tumor-targeted fusion gene product were generated and administered locally and systemically via electroporation. As anticipated, administration of a therapeutic gene encoding IFN-alpha and the tumor vessel-targeted peptide CDGRC fusion gene product minimizes the leakage of immunostimulatory cytokine from tumors into the blood circulation, increases the infiltration of CD8(+) T cells into tumors, induces a high magnitude of cytotoxic T-cell lysis (CTL) activity, and reduces tumor vessel density. As a result, tumor growth was more significantly inhibited by administering the IFN-alpha-CDGRC gene than by administering the wild-type IFN-alpha gene. The same result was obtained with the systemic administration of the tumor-targeted IFN-alpha gene. This gene product-based tumor-targeted gene therapy approach could complement any other tumor-targeted gene delivery method for improving tumor-targeting efficiency. FAU - Craig, Ryan AU - Craig R AD - Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA. FAU - Cutrera, Jeffry AU - Cutrera J FAU - Zhu, Shiguo AU - Zhu S FAU - Xia, Xueqing AU - Xia X FAU - Lee, Yong-Hwan AU - Lee YH FAU - Li, Shulin AU - Li S LA - eng GR - R01CA120895/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20080318 PL - United States TA - Mol Ther JT - Molecular therapy : the journal of the American Society of Gene Therapy JID - 100890581 RN - 0 (Interferon-alpha) RN - 9007-49-2 (DNA) RN - EC 3.4.11.2 (CD13 Antigens) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - CD13 Antigens/biosynthesis MH - CD8-Positive T-Lymphocytes/metabolism MH - DNA/*chemistry MH - Female MH - *Gene Transfer Techniques MH - Genetic Therapy/*methods MH - Interferon-alpha/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C3H MH - Molecular Sequence Data MH - Plasmids/*metabolism EDAT- 2008/04/05 09:00 MHDA- 2008/08/20 09:00 CRDT- 2008/04/05 09:00 PHST- 2008/04/05 09:00 [pubmed] PHST- 2008/08/20 09:00 [medline] PHST- 2008/04/05 09:00 [entrez] AID - S1525-0016(16)31704-X [pii] AID - 10.1038/mt.2008.40 [doi] PST - ppublish SO - Mol Ther. 2008 May;16(5):901-6. doi: 10.1038/mt.2008.40. Epub 2008 Mar 18.