2.
Cellular targets of ER intrabodies
| ER Intrabodies inhibiting oncogenic proteins | ||||
|---|---|---|---|---|
| Target | Target function | Cellular targets | Performance | References |
| Human IL-2 receptor | Signal transduction | Jurkat T cells | In vitro studies with intrabody plasmid | [29] |
| Human IL-2 receptor | Signal transduction | T-cell leukaemia cell line, HTLV-1 transformed cell lines and primary human T cells | In vitro studies with tetracycline responsible intrabody plasmid and HIV-1-based lentivirus vector | [30, 31] |
| ErbB-2 | Signal transduction | NIH/3T3 cells expressing human erbB-2 and mammary carcinoma cells | In vitro studies with murine leukaemia virus vector | [32, 33] |
| ErbB-2 | Signal transduction | Human breast cancer and ovarian carcinoma cell lines | In vitro studies with recombinant adenovirus and intrabody plasmid | [34, 35] |
| ErbB-2 | Signal transduction | Human ovarian carcinoma cells transplanted in SCID mice | In vivo studies with recombinant adenovirus | [36] |
| ErbB-2 | Signal transduction | Human ovarian cancer cells | Phase I study with ovarian cancer patients performed with recombinant adenovirus | [37] |
| ErbB-2 | Signal transduction | Human erbB-2-positive tumour cell lines | In vitro study with intrabody plasmid containing a high affinity anti-erbB-2 scFv fragment | [38] |
| ErbB-2/androgen receptor | Signal transduction | Human prostate cancer tumour cell line | In vitro studies with murine leukaemia virus vector | [39] |
| EGFR | Signal transduction | Human tumour cell lines overexpressing EGFR | In vitro studies with murine leukaemia virus vector | [40] |
| VEGFR-2/KDR | Signal transduction | Porcine aortic endothelial cells overexpressing humanVEGFR-2 | In vitro studies with intrabody plasmid | [41] |
| VEGFR-2/KDR | Signal transduction | HUVECs | In vitro studies with recombinant adenovirus | [42] |
| Tie-2 | Signal transduction | Mouse model with Kaposi's sarcoma and human colon carcinoma xenografts | In vivostudies with adenovirus-delivered anti-Tie-2 intrabody | [43] |
| VEGFR-2/KDR-Tie-2 | Signal transduction | Mouse model with human melanoma xenografts | In vivo studies with adenovirus-delivered anti-VEGFR-2-Tie-2 intradiabody | [44, 45] |
| Human α folate receptor | Signal transduction | Human ovarian carcinoma cell lines | In vitro studies with intrabody plasmid | [46] |
| Cathepsin L | Endopeptidase | Human melanoma cell lines | In vitro studies with intrabody plasmid | [81] |
| Metalloproteinase MMP-2 and MMP-9 | Degradation of collagen IV | Human lung carcinoma cell line | In vitro studies with intrabody plasmid | [82] |
| ER intrabodies targeting HIV-1 gp160/gp120 and HIV-1 co-receptors | ||||
| Target | Target function | Cellular targets | Performance | References |
| HIV-1 gp120 | Viral coat protein | Human lymphocytes and CD4+ T cells from HIV-positive patients | In vitro studies with recombinant adeno-associated virus and murine leukaemia virus vector | [47, 48] |
| HIV-1 gp160 | Viral coat protein | CD4+ human T cells (Jurkat) | In vitro studies with intrabody plasmid | [49] |
| CCR5 | HIV-1 co-receptor | CCR5+/CD4+ human lymphocyte cell line | In vitro studies with murine leukaemia virus vector | [50] |
| CCR5 | HIV-1 co-receptor | CD34+ fetal liver stem cells | In vitro studies with HIV-1-derived self-inactivating lentivirus vector and in vivo studies with NOD/SCID mice transduced with the intrabody expressing CD34+ fetal liver stem cells | [51] |
| CCR5 | HIV-1 co-receptor | Human monocyte-derived macrophages and microglia cells from human fetal brain tissue | In vitro studies with Tag-deleted SV40-derived vector and hammerhead CCR5 specific ribozyme | [52] |
| CXCR4 | HIV-1 co-receptor | CD4+Human T lymphocytic cell line and HeLa-CD4/ βgal-CCR5 cells | In vitro studies with murine leukemia virus and SV40-based virus vector | [53] |
| CXCR4 | HIV-1 co-receptor | Primary human brain microvascular endothelial cells and post-mitotic differentiated human neurons | In vitro studies with HIV-1-based lentivirus vector | [54] |
| ER intrabodies targeting other viruses as HIV-1 | ||||
| Target | Target function | Cellular targets | Performance | References |
| Hepatitis C virus core protein | Viral core protein | Human hepatocellular carcinoma cell line and HEK 293 cells | In vitro studies with intrabody plasmid | [83] |
| Maedi-visna virus gp46 protein | Envelope glycoprotein | Sheep choroid plexus cell line | In vitro studies with the soluble scFv fragment, intracellular ER expression of the antibody is planned | [84] |
| Root-knot nematode Meloidogyne incognita | Nematoide in fection | Tobacco leaf protoplasts | In vitro studies with intrabody plasmid | [85] |
| ER intrabodies abrogating antigen presenting molecules | ||||
| Target | Target function | Cellular targets | Performance | References |
| MHC I | Antigen presentation | Primary rat keratinocytes | In vitro studies with intrabody plasmids | [55] |
| MHC I | Antigen presentation | Human CD4+ Jurkat T-cell line, human primary keratinocytes and several cell lines of divergent tissue sources | In vitro studies with intrabody plasmid and recombinant adenovirus | [56] |
| MHC I | Antigen presentation | Human umbilical vein endothelial cells | In vitro studies with recombinant adenovirus | [57] |
| α1,3-Galactosyl-transferase | Glycosylation | Pig epithelial kidney cells | In vitro studies with intrabody plasmid | [87] |
| ER intrabodies targeting integrins | ||||
| Target | Target function | Cellular target | Performance | References |
| αV integrin | Mediation of cell-cell and cellmatrix interactions | Saos-2 human osteosarcoma cell line and WM-266-4 melanoma cell line | In vitro studies with intrabody plasmid | [58, 59] |
| αV integrin | Mediation of cell-cell and cell-matrix interactions | Human metastatic melanoma cell lines and xenograft melanoma SCID mouse model | In vitro and in vivo studies with recombinant adenovirus | [60] |
| ER Intrabodies targeting proteins involved in Alzheimer's and Prion disease | ||||
| Target | Target function | Cellular target | Performance | References |
| Human β-amy-loid precursor protein (APP) | Transmembrane protein involved in the pathogenesis of Alzheimer's disease | HEK 293 cells transient transfected with cDNA of human APP | In vitro studies with intrabody plasmid | [28] |
| Cellular prion protein | Pathogenesis of Prion diseases | Nerve growth factor-differentiated PC12 cells infected with a suspension of mouse brains from scrapie-affected mice and scrapie mouse model | In vitro and in vivo studies with PC 12 cells stably expressing the intrabody | [61, 62] |