TY  - JOUR
AB  - Adoptive T-cell therapy using natural T-cell receptor (TCR) redirection is a promising approach to fight solid cancers and viral infections in liver and other organs. However, clinical efficacy of such TCR+-T cells has been limited so far. One reason is that syngeneic preclinical models to evaluate safety and efficacy of TCR+-T cells are missing. We therefore developed an efficient viral vector strategy mediating expression of human MHC-I in hepatocytes, which allows evaluation of TCR-T cell therapies targeting diseased liver cells. We designed adeno-associated virus (AAV) and adenoviral vectors encoding either the human-mouse chimeric HLA-A*02-like molecule HHD, or fully human HLA-A*02 and human 2 microglobulin (h2m). Upon transduction of murine hepatocytes, the HLA-A*02 construct proved superior in terms of expression levels, presentation of endogenously processed peptides and activation of murine TCR+-T cells grafted with HLA-A*02-restricted, hepatitis B virus (HBV)-specific TCRs. In vivo, these T cells elicited effector function, controlled HBV replication, reduced HBV viral load and antigen expression specifically in livers of mice that had received AAV-HBV and AAV-HLA-A*02. We then demonstrated the utility of this approach by expressing the HBV-specific TCRs on macaque primary T cells enabling them to recognize HBV-infected macaque hepatocytes expressing HLA-A*02 upon adenoviral transduction. In conclusion, AAV and adenovirus vectors are suitable for delivery of HLA-A*02 and h2m into mouse and macaque hepatocytes. When recognizing HBV in the HLA-A*02-transduced mouse livers or on macaque hepatocytes, HLA-A*02-restricted, HBV-specific TCR+-T cells become activated and exert antiviral effector functions. This approach is applicable to other MHC restrictions and target diseases, paving the way for safety and efficacy studies of human TCR-based therapies in physiologically relevant preclinical animal models.
AU  - Festag, J.
AU  - Festag, M.M.*
AU  - Asen, T.
AU  - Wettengel, J.*
AU  - Mück-Häusl, M.
AU  - Abdulhaqq, S.*
AU  - Stahl-Hennig, C.*
AU  - Sacha, J.*
AU  - Burwitz, B.*
AU  - Protzer, U.
AU  - Wisskirchen, K.
C1  - 68641
C2  - 54842
CY  - 140 Huguenot Street, 3rd Fl, New Rochelle, Ny 10801 Usa
SP  - 1204-1218
TI  - Vector-mediated delivery of human MHC-I into hepatocytes enables investigation of TCR-redirected HBV-specific T cells in mice and macaque cell cultures.
JO  - Hum. Gene Ther.
VL  - 34
IS  - 23-24
PB  - Mary Ann Liebert, Inc
PY  - 2023
SN  - 1043-0342
ER  - 

TY  - JOUR
AB  - Epstein-Barr virus (EBV) infections in healthy individuals are usually cleared by immune cells, wherein CD8+ T cells play the most important role. However, in some immunocompromised individuals, EBV infections can lead to the development of cancer in B, T, NK cells and epithelial cells. Most EBV-associated cancers express a limited number of virus-specific antigens such as latent membrane proteins (LMP1, LMP2) and nuclear proteins (EBNA1, -2, EBNA3A, -B, -C, EBNA-LP). These antigens represent true tumor-specific antigens and can be considered useful targets for TCR gene therapy to treat EBV-associated diseases. We used a TCR isolation platform based on a single major histocompatibility class I complexe (MHC I) K562 cell library for the detection, isolation, and re-expression of TCRs targeting immunodominant peptide-MHC (pMHC) complexes. Mature dendritic cells (mDCs) were pulsed with in vitro-transcribed (ivt) RNA encoding for the selected antigen to stimulate autologous T cells. The procedure allowed the mDCs to select an immunogenic epitope of the antigen for processing and presentation on the cell surface in combination with the most suitable MHC I molecule. We isolated eight EBV-specific TCRs. They recognize various pMHC complexes of EBV antigens LMP1, LMP2A, and EBNA3C, some of them described previously and some newly identified in this study. The TCR genes were molecularly cloned into retroviral vectors and the resultant TCR-engineered T cells secreted interferon-γ after antigen contact and were able to lyse tumor cells. The EBV-specific TCRs can be used as a basis for the generation of a TCR library, which provides a valuble source of TCRs for the production of EBV-specific T cells to treat EBV-associated diseases in patients with different MHC I types.
AU  - Dudaniec, K.*
AU  - Westendorf, K.*
AU  - Nößner, E.
AU  - Uckert, W.*
C1  - 61746
C2  - 50441
CY  - 140 Huguenot Street, 3rd Fl, New Rochelle, Ny 10801 Usa
SP  - 919-935
TI  - Generation of Epstein-Barr virus antigen-specific T cell receptors recognizing immunodominant epitopes of LMP1, LMP2A, and EBNA3C for immunotherapy.
JO  - Hum. Gene Ther.
VL  - 32
IS  - 17-18
PB  - Mary Ann Liebert, Inc
PY  - 2021
SN  - 1043-0342
ER  - 

TY  - JOUR
AB  - Coxsackievirus B3 (CVB3) has strong oncolytic activity in colorectal carcinoma but it also infects the pancreas and the heart. To improve the safety of the virus, here we investigated whether pancreas and cardiac toxicity can be prevented by insertion of target sites (TS), which are complementary to miR-375 and miR-1 into the viral genome. Although miR-375 and miR-1 are abundantly expressed in the pancreas and in the heart, respectively, their expression levels are low in colorectal carcinomas, which allows the carcinomas to be selectively attacked. To investigate the importance of the microRNAs, two viruses were engineered, H3N-375TS containing only miR-375TS and H3N-375/1TS containing miR-375TS and miR-1TS. In vitro, both viruses replicated in and lysed colorectal carcinoma cells, similar to a nontargeted control virus H3N-39TS, whereas they were strongly attenuated in cell lines transiently or endogenously expressing the corresponding microRNAs. In vivo, the control virus H3N-39TS induced strong infection of the pancreas and the heart, which led to fatal disease within 4 days after a single intratumoral virus injection in mice xenografted with colorectal DLD-1 cell tumors. In contrast, three intratumoral injections of H3N-375TS or H3N-375/1TS failed to induce virus-induced sickness. In the animals, both viruses were completely ablated from the pancreas and H3N-375/1TS was also ablated from the heart, whereas the cardiac titers of H3N-375TS were strongly reduced. Long-term investigations of the DLD-1 tumor model confirmed lack of virus-induced adverse effects in H3N-375TS- and H3N-375/1TS-treated mice. There was no mortality, and the pancreas and the heart were free of pathological alterations. Regarding the therapeutic efficiency, the treated animals showed high and long-lasting H3N-375TS and H3N-375/1TS persistence in the tumor and significantly slower tumor growth. These data demonstrate that miR-375- and miR-1-mediated virus detargeting from the pancreas and heart is a highly effective strategy to prevent toxicity of oncolytic CVB3.
AU  - Hazini, A.*
AU  - Dieringer, B.*
AU  - Pryshliak, M.*
AU  - Knoch, K.-P.
AU  - Heimann, L.*
AU  - Tolksdorf, B.*
AU  - Pappritz, K.*
AU  - El-Shafeey, M.*
AU  - Solimena, M.
AU  - Beling, A.*
AU  - Kurreck, J.*
AU  - Klingel, K.*
AU  - Fechner, H.*
C1  - 61065
C2  - 50026
CY  - 140 Huguenot Street, 3rd Fl, New Rochelle, Ny 10801 Usa
SP  - 216-230
TI  - miR-375- and miR-1-regulated coxsackievirus B3 has no pancreas and heart toxicity but strong antitumor efficiency in colorectal carcinomas.
JO  - Hum. Gene Ther.
VL  - 32
IS  - 3-4
PB  - Mary Ann Liebert, Inc
PY  - 2021
SN  - 1043-0342
ER  - 

TY  - JOUR
AU  - Schreiber, S.
AU  - Honz, M.
AU  - Schiemann, M.*
AU  - Sette, A.*
AU  - Zielinski, C.
AU  - Protzer, U.
AU  - Wisskirchen, K.
C1  - 57785
C2  - 47912
CY  - 140 Huguenot Street, 3rd Fl, New Rochelle, Ny 10801 Usa
SP  - A10-A10
TI  - Characterization of MHC class II-restricted t-cell receptors for t-cell therapy of HBV infection.
JO  - Hum. Gene Ther.
VL  - 30
IS  - 12
PB  - Mary Ann Liebert, Inc
PY  - 2019
SN  - 1043-0342
ER  - 

TY  - JOUR
AU  - Festag, M.
AU  - Wisskirchen, K.
AU  - Hasreiter, J.
AU  - Schreiber, S.
AU  - Abken, H.*
AU  - Protzer, U.
C1  - 54829
C2  - 45897
CY  - 140 Huguenot Street, 3rd Fl, New Rochelle, Ny 10801 Usa
SP  - A4-A4
TI  - Evaluation of a fully human car for the treatment of hepatitis B virus infection in an immunocompetent mouse model.
JO  - Hum. Gene Ther.
VL  - 29
IS  - 11
PB  - Mary Ann Liebert, Inc
PY  - 2018
SN  - 1043-0342
ER  - 

TY  - JOUR
AB  - T-cell receptor (TCR) immunotherapy uses T cells engineered with new TCRs to enable detection and killing of cancer cells. Efficacy of TCR immunotherapy depends on targeting antigenic peptides that are efficiently presented by the best-suited major histocompatibility complex (MHC) molecules of cancer cells. However, efficient strategies are lacking to easily identify TCRs recognizing immunodominant peptide-MHC (pMHC) combinations utilizing any of the six possible MHC class I alleles of a cancer cell. We generated an MHC cell library and developed a platform approach to detect, isolate, and re-express TCRs specific for immunodominant pMHCs. The platform approach was applied to identify a human papillomavirus (HPV16) oncogene E5-specific TCR, recognizing a novel, naturally processed pMHC (HLA-B*15:01) and a cytomegalovirus-specific TCR targeting an immunodominant pMHC (HLA-B*07:02). The platform provides a useful tool to isolate in an unbiased manner TCRs specific for novel and immunodominant pMHC targets for use in TCR immunotherapy.
AU  - Lorenz, F.K.*
AU  - Ellinger, C.
AU  - Kieback, E.*
AU  - Wilde, S.
AU  - Lietz, M.*
AU  - Schendel, D.J.
AU  - Uckert, W.*
C1  - 52539
C2  - 44053
CY  - New Rochelle
SP  - 1158-1168
TI  - Unbiased identification of T-cell receptors Targeting immunodominant peptide-MHC complexes for T-cell receptor immunotherapy.
JO  - Hum. Gene Ther.
VL  - 28
IS  - 12
PB  - Mary Ann Liebert, Inc
PY  - 2017
SN  - 1043-0342
ER  - 

TY  - JOUR
AU  - Wisskirchen, K.
AU  - Kah, J.*
AU  - Malo, A.
AU  - Allweiss, L.*
AU  - Volz, T.*
AU  - Dandri, M.*
AU  - Protzer, U.
C1  - 52669
C2  - 44451
CY  - New Rochelle
SP  - A30-A30
TI  - Hepatitis B virus (HBV)-specific T cell receptors with high functional avidity redirect T cells to eliminate HBV.
JO  - Hum. Gene Ther.
VL  - 28
IS  - 12
PB  - Mary Ann Liebert, Inc
PY  - 2017
SN  - 1043-0342
ER  - 

TY  - JOUR
AU  - Geiger, S.*
AU  - Hereth, M.*
AU  - Forster, D.*
AU  - Hollauer, C.
AU  - Ballester, C.F.
AU  - Hermann, F.G.*
AU  - Yildirim, A.Ö.*
AU  - Guenther, C.*
C1  - 50118
C2  - 42115
CY  - New Rochelle
SP  - A34-A34
TI  - Amelioration of lung function and pulmonary tissue regeneration after treatment with Alpha-1 antitrypsin (AAT)-expressing mesenchymal stem cells (MSCs) in a murine model of elastase-induced emphysema.
JO  - Hum. Gene Ther.
VL  - 27
IS  - 11
PB  - Mary Ann Liebert, Inc
PY  - 2016
SN  - 1043-0342
ER  - 

TY  - JOUR
AU  - Conde, J.*
AU  - Ambrosone, A.*
AU  - Hernandez, Y.*
AU  - Marchesano, V.*
AU  - Tian, F.
AU  - Ricardo Ibarra, M.*
AU  - Baptista, P.V.*
AU  - Tortiglione, C.*
AU  - de la Fuente, J.M.*
C1  - 29247
C2  - 33784
SP  - A24
TI  - Designing gold nanoparticles for in vivo gene silencing as a new therapeutic tool.
JO  - Hum. Gene Ther.
VL  - 24
IS  - 12
PB  - Mary Ann Liebert, Inc
PY  - 2013
SN  - 1043-0342
ER  - 

TY  - CONF
AU  - Morscher, S.
AU  - Stritzker, J.*
AU  - Kirscher, L.*
AU  - Deliolanis, N.C.
AU  - Symvoulidis, P.
AU  - Schaefer, K.
AU  - Zhang, Q.*
AU  - Donat, U.*
AU  - Ntziachristos, V.
AU  - Szalay, A.A.*
C1  - 25526
C2  - 32607
SP  - A16
TI  - Imaging virus-mediated melanin production using Multispectral Optoacoustic Tomography (MSOT).
JO  - Hum. Gene Ther.
VL  - 24
IS  - 5
PB  - Mary Ann Liebert Inc.
PY  - 2013
SN  - 1043-0342
ER  - 

TY  - JOUR
AB  - Preclinical studies showed that the allogeneic tumor cell line RCC-26 displayed natural immunogenic potential that was enhanced through expression of CD80 costimulatory molecules and secretion of interleukin-2. Here we report the study of RCC-26/CD80/IL-2 cells in a phase 1 vaccine trial of renal cell carcinoma patients with metastatic disease (mRCC). Fifteen patients of the HLA-A*0201 allotype, with at least one metastatic lesion, were included. Irradiated vaccine cells were applied in increasing doses of 2.5, 10, and 40 x 10(6) cells over 22 weeks. Primary study parameters included safety and toxicity. Sequential blood samples were analyzed by interferon-gamma enzyme-linked immunospot assays to detect tumor antigen-associated (TAA) effector cells. The vaccine was well tolerated and the designated vaccination course was completed in 9 of 15 patients. Neither vaccine-induced autoimmunity nor systemic side effects were observed. Delayed-type hypersensitivity skin reactions were detected in 11 of 12 evaluated patients and were particularly strong in patients with prolonged survival. In parallel, vaccine-induced immune responses against vaccine or overexpressed TAA were detected in 9 of 12 evaluated patients. No tumor regressions occurred according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria; however, median time to progression was 5.3 months and median survival was 15.6 months, indicating substantial disease stabilization. We conclude that vaccine use was safe and feasible in mRCC. Clinical benefits were limited in these patients with advanced disease; however, immune monitoring revealed vaccine-induced responses against multiple TAAs in the majority of study participants. These results suggest that this vaccine could be useful in combination therapies and/or minimal residual disease.
AU  - Buchner, A.*
AU  - Pohla, H.
AU  - Willimsky, G.*
AU  - Frankenberger, B.
AU  - Frank, R.
AU  - Baur-Melnyk, A.*
AU  - Siebels, M.*
AU  - Stief, C.G.*
AU  - Hofstetter, A.*
AU  - Kopp, J.*
AU  - Pezzutto, A.*
AU  - Blankenstein, T.*
AU  - Oberneder, R.*
AU  - Schendel, D.J.
C1  - 1110
C2  - 27078
SP  - 285-297
TI  - Phase 1 trial of allogeneic gene-modified tumor cell vaccine RCC-26/CD80/IL-2 in patients with metastatic renal cell carcinoma.
JO  - Hum. Gene Ther.
VL  - 21
IS  - 3
PB  - Mary Ann Liebert
PY  - 2010
SN  - 1043-0342
ER  - 

TY  - JOUR
AU  - Stocking, C.*
AU  - Grez, M.*
AU  - Fehse, B.*
AU  - von Laer, D.*
AU  - Itoh, K.*
AU  - Prassolov, V.*
AU  - Nowock, J.*
AU  - Kühlcke, K.*
AU  - Just, U.*
AU  - Schroeder, T.
AU  - Klump, H.*
AU  - Schiedlmeier, B.*
AU  - Grassman, E.*
AU  - Meyer, J.*
AU  - Li, Z.*
AU  - Schambach, A.*
AU  - Modlich, U.*
AU  - Kustikova, O.*
AU  - Galla, M.*
AU  - Bode, J.*
AU  - Zander, A.*
AU  - Baum, C.*
C1  - 23468
C2  - 31037
SP  - 1501-1503
TI  - Cell and virus genetics at the roots of gene therapy, retrovirology, and hematopoietic stem cell biology: Wolfram Ostertag (1937-2010).
JO  - Hum. Gene Ther.
VL  - 21
IS  - 11
PB  - Mary Ann Liebert, Inc.
PY  - 2010
SN  - 1043-0342
ER  - 

TY  - JOUR
AB  - Immunotherapy with whole cell cancer vaccines has been tested in various tumor types. This study investigated the safety profile and antitumor activity of an allogeneic prostate carcinoma cell line, LNCaP, expressing recombinant human interleukin-2 and human interferon-gamma. Thirty HLA-A*0201-matched patients with progressive, castration-resistant prostate cancer received four intradermal injections on days 1, 15, 29, and 92, and then every 90 days, as long as no tumor progression occurred. Three patients received a dose level of 7.5 million cells, and 27 patients received 15 million cells per injection. The primary study criteria were safety and the difference in prostate-specific antigen doubling time (PSA-DT), determined in the pretreatment phase (before the start of vaccination) and in the trial treatment phase (during vaccination). No dose-limiting or autoimmune toxicity was seen. During vaccination there was a significant prolongation of the PSA-DT compared with the prevaccination period (prolongation from 63 to 114 days; p < 0.01; intention to treat). In addition, results showed a period of PSA stabilization of at least 12 weeks, together with stable bone scans in 12 of 30 patients, and 3 patients sustained a >50% decrease in PSA versus baseline. The median overall survival time from first vaccination was 32 months (mean value, 34 months). Immune monitoring revealed T cell stimulation in the majority of patients. This vaccine strategy was found to be safe and well tolerated and was accompanied by prolongation of PSA-DT. The results of this trial warrant clinical development of this vaccine.
AU  - Brill, T.H.*
AU  - Kübler, H.R.*
AU  - Pohla, H.
AU  - Buchner, A.*
AU  - Fend, F.*
AU  - Schuster, T.*
AU  - van Randenborgh, H.*
AU  - Paul, R.*
AU  - Kummer, T.*
AU  - Plank, C.*
AU  - Eisele, B.*
AU  - Breul, J.*
AU  - Hartung, R.*
AU  - Schendel, D.J.
AU  - Gansbacher, B.*
C1  - 1613
C2  - 26596
SP  - 1-11
TI  - Therapeutic vaccination with an Interleukon-2-Iinterferon-γ-secreting allogeneic tumor vaccine in patients with progressive castration-resistant prostate cancer - a phase I/II trial.
JO  - Hum. Gene Ther.
VL  - 20
IS  - 12
PB  - Mary Ann Liebert
PY  - 2009
SN  - 1043-0342
ER  - 

TY  - JOUR
AB  - Therapeutic neovascularization is a concept well validated in animal models, however, without clear-cut success in clinical studies. To achieve prolonged transgene expression, recombinant adeno-associated virus (rAAV) was used in a chronic ischemic hind-limb model and the human antimicrobial peptide cathelicidin (LL-37/hCAP-18) was used as proangiogenic factor. Seven days after femoral artery excision, 0.5 x 10 11 rAAV particles encoding for green fluorescent protein ( rAAV. GFP), cathelicidin ( rAAV. cath), or vascular endothelial growth factor A ( rAAV. VEGF-A) were retroinfused into the anterior tibial vein of rabbits (n = 5 per group). In addition, one rAAV. cath-treated group obtained a constant infusion with the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin into the ischemic tissue starting on day 7. On day 7 and day 35 angiography of both hind limbs was performed for collateral quantification and frame count score (cinedensitometry). Capillary-to-muscle fiber ratios were obtained on day 35. Compared with controls, application of rAAV. cath induced a gain of perfusion ( 153 +/- 12 vs. 107+9% of day 7 controls) via increased collateral growth ( length index, 161 +/- 14 vs. 97 +/- 9%, controls), but no significant capillary growth (1.16 +/- 0.09 vs. 0.99 +/- 0.08, controls). Wortmannin application completely abolished the effects of rAAV. cath, indicating the involvement of the PI3K signal pathway. In conclusion, rAAV-mediated cathelicidin expression is capable of inducing functionally relevant neovascularization, preferentially by collateral growth. The rAAV-based vectors as long-expressing vector expression systems and cathelicidin as proangiogenic factor provide a promising new combination in the treatment of peripheral artery disease.
AU  - Pinkenburg, O.*
AU  - Pfosser, A.*
AU  - Hinkel, R.*
AU  - Böttcher, M.*
AU  - Dinges, C.*
AU  - Lebherz, C.*
AU  - Sultana, S.*
AU  - Enssle, J.
AU  - El-Aouni, C.*
AU  - Buning, H.*
AU  - Boekstegers, P.*
AU  - Bals, R.*
AU  - Kupatt, C.*
C1  - 2509
C2  - 26417
SP  - 159-167
TI  - Recombinant adeno-associated virus-based gene transfer of cathelicidin induces therapeutic neovascularization preferentially via potent collateral growth.
JO  - Hum. Gene Ther.
VL  - 20
IS  - 2
PB  - Mary Ann Liebert Inc
PY  - 2009
SN  - 1043-0342
ER  - 

TY  - JOUR
AB  - Locoregional hyperthermia (HT) can be used for site-directed activation of macromolecular drug delivery systems. We have developed a gene delivery system based on thermosensitive block copolymers (TSCs) with a phase transition temperature of 42 degrees C [Zintchenko, A., Ogris, M., and Wagner, E. (2006). Bioconjug. Chem. 17, 766-772], in which the statistical copolymer of vinylpyrrolidinone and N-isopropylacryamide is grafted on polyethylenimine (PEI). Here we applied polyplexes consisting of plasmid DNA and TSCs systemically in A/J mice bearing a syngeneic Neuro2A neuroblastoma tumor subcutaneously in each hind limb. One limb was selectively treated by HT at 42 degrees C, at the same time that polyplexes were injected via the tail vein. Hyperthermia led to increased accumulation of thermosensitive polymer and aggregation of thermosensitive polyplexes in HT-treated tumors, resulting in up to 10-fold increased DNA deposition compared with non-HT-treated tumor. The level of transgene expression induced by TSC polyplexes in HT-treated tumors was significantly higher and selective for tumor tissue. With nonthermosensitive PEI polyplexes HT did not influence transgene deposition or expression in tumor.
AU  - Schwerdt, A.*
AU  - Zintchenko, A.*
AU  - Concia, M.*
AU  - Roesen, N.*
AU  - Fisher, K.*
AU  - Lindner, L.H.
AU  - Issels, R.D.
AU  - Wagner, E.*
AU  - Ogris, M.*
C1  - 2616
C2  - 26027
SP  - 1283-1292
TI  - Hyperthermia-induced targeting of thermosensitive gene carriers to tumors.
JO  - Hum. Gene Ther.
VL  - 19
IS  - 11
PB  - Mary Ann Liebert Inc.
PY  - 2008
SN  - 1043-0342
ER  - 

TY  - JOUR
AB  - Until recently, adenovirus-based gene therapy has been almost exclusively based on human adenovirus serotype 5 (Ad5). The aim of this study was to systematically compare the efficiency of transduction of primary muscle cells from various species by two adenoviral vectors from subgroups C and D. Transduction of a panel of myoblasts demonstrated a striking specificity of an Ad19a-based replication-defective E1-deleted vector (Ad19aEGFP) for human cells, whereas the Ad5-based vector had high affinity for nonhuman primate myoblasts. Transgene expression correlated well with cell-associated vector genomes. Up to 6.59% of the initially applied Ad19aEGFP vector particles were taken up by human myoblasts, as compared with 0.1% of the corresponding Ad5 vector. Remarkably, Ad19aEGFP but not Ad5EGFP efficiently transduced differentiated human myotubes, an in vitro model for skeletal muscle transduction. Uptake of Ad19aEGFP vector particles in human myotubes was 12-fold more efficient than that of Ad5EGFP. Moreover, both vectors demonstrated an early block at the level of vector uptake in mouse myoblasts and rat L6 cells. Investigation of the underlying mechanism for binding and uptake of the two vectors by human myoblasts showed high susceptibility for Ad19a to neuraminidase and wheat germ agglutinin (WGA) lectin, whereas Ad5-mediated transduction was dependent on binding to the coxsackie-adenovirus receptor (CAR) and sensitive to soluble RGD peptide and heparin. Our study offers insights into species-dependent factors that determine Ad tropism and, moreover, provides a basis for application of the novel Ad19a-based vector for gene transfer into human skeletal muscle.
AU  - Thirion, C.*
AU  - Lochmüller, H.*
AU  - Ruzsics, Z.*
AU  - Boelhauve, M.*
AU  - König, C.*
AU  - Thedieck, C.*
AU  - Kutik, S.*
AU  - Geiger, C.
AU  - Kochanek, S.*
AU  - Volpers, C.*
AU  - Burgert, H.-G.*
C1  - 1426
C2  - 24196
SP  - 193-205
TI  - Adenovirus vectors based on human adenovirus type 19a have high potential for human muscle-directed gene therapy.
JO  - Hum. Gene Ther.
VL  - 17
IS  - 2
PY  - 2006
SN  - 1043-0342
ER  - 

TY  - JOUR
AU  - Engels, B.*
AU  - Nößner, E.
AU  - Frankenberger, B.
AU  - Blankenstein, T.*
AU  - Schendel, D.J.
AU  - Uckert, W.*
C1  - 1003
C2  - 23071
SP  - 799-810
TI  - Redirecting Human T Lymphocytes toward Renal Cell Carcinoma Specificity by Retroviral Transfer of T Cell Receptor Genes.
JO  - Hum. Gene Ther.
VL  - 16
PY  - 2005
SN  - 1043-0342
ER  - 

TY  - JOUR
AU  - di Nicola, M.*
AU  - Carlo-Stella, C.*
AU  - Anichini, A.*
AU  - Mortarini, R.*
AU  - Guidetti, A.*
AU  - Tragni, G.*
AU  - Gallino, F.*
AU  - del Vecchio, M.*
AU  - Ravagnani, F.*
AU  - Morelli, D.*
AU  - Chaplin, P.*
AU  - Arndtz, N.*
AU  - Sutter, G.
C1  - 9429
C2  - 21628
SP  - 1347-1360
TI  - Immunization of Patients with Malignant Melanoma with Autologous CD34+ Cell-Derived Dendritic Cells Transduced Ex Vivo with a Recombinant Replication-Deficient Vaccinia Vector Encoding the Human Tyrosinase Gene : A Phase I Trial.
JO  - Hum. Gene Ther.
VL  - 14
PY  - 2003
SN  - 1043-0342
ER  - 

TY  - JOUR
AB  - Transplantation of dopaminergic fetal mesencephalic tissue into the striatum is currently being developed for treatment of patients with advanced Parkinson's disease. Ethical concerns regarding the use of human fetal tissue, and the limited availability as well as poor survival and differentiation of dopaminergic neurons after transplantation have reduced the extent and outcome of this approach so far. With the purpose of finding means to increase the yield of dopaminergic neurons in transplants, and to reduce the amount of fetal tissue needed for each transplanted patient, we transfected rat fetal ventral mesencephalic (VM) tissue grown as organotypic free-floating roller tube (FFRT) cultures with a vector encoding human glial cell-derived neurotrophic factor (hGDNF). For transfer of an episomal expression vector (pRep7-GDNF8) a nonviral, nonliposomal cationic transfection technique was applied and optimized. Recombinant hGDNF expression resulted in a higher number of TH-positive neurons in the cultures as measured 6 days after transfection. Ventral mesencephalic cultures expressing hGDNF were then grafted into the striatum of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. Grafting of genetically modified VM cultures resulted in earlier functional recovery compared with grafting nontransfected cultures. We conclude that organotypic free-floating roller tube cultures can be successfully transfected to produce hGDNF with effects on TH-expressing neurons in vitro and functional effects after grafting in a rat Parkinson's disease model.
AU  - Bauer, M.
AU  - Meyer, M.*
AU  - Grimm, L.*
AU  - Meitinger, T.*
AU  - Zimmer, J.
AU  - Gasser, T.*
AU  - Ueffing, M.
AU  - Widmer, H.R.*
C1  - 23782
C2  - 31405
SP  - 1529-1541
TI  - Nonviral glial cell-derived neurotrophic factor gene transfer enhances survival of cultured dopaminergic neurons and improves their function after transplantation in a rat model of Parkinson's disease.
JO  - Hum. Gene Ther.
VL  - 11
IS  - 11
PB  - Mary Ann Liebert Inc.
PY  - 2000
SN  - 1043-0342
ER  - 

TY  - JOUR
AU  - Salmons, B.
AU  - Günzburg, W.H.
C1  - 19829
C2  - 12978
SP  - 129-141
TI  - Targeting of Retroviral Vectors for Gene Therapy.
JO  - Hum. Gene Ther.
VL  - 4
PY  - 1993
SN  - 1043-0342
ER  - 

TY  - JOUR
AB  - Retroviral vectors are one of the most promising vehicles for the delivery of therapeutic genes in human gene therapy protocols. Retroviral-mediated gene transfer currently being used in human clinical trials is based upon ex vivo transduction of target cells. The ability to target the delivery and expression of therapeutic genes in vivo using retroviral vectors is a prerequisite for widespread and routine use in the clinic and will be of great importance for the safe and successful treatment of certain genetic disorders as well as tumors and viral infections. A number of approaches have been taken to develop retroviral vectors that are able to target particular cell types both at the level of the transduction event and at the level of expression. Using various combinations of the restrictive features reviewed in this article, it should be possible to achieve definitive targeting of genes transduced by retroviral vectors.
AU  - Salmons, B.*
AU  - Günzburg, W.H.
C1  - 40344
C2  - 38977
SP  - 129-141
TI  - Targeting of retroviral vectors for gene therapy.
JO  - Hum. Gene Ther.
VL  - 4
IS  - 2
PY  - 1993
SN  - 1043-0342
ER  -