Reference - Detail
| RRC ID | 4759 |
|---|---|
| Author | Sogo T, Kawahara M, Tsumoto K, Kumagai I, Ueda H, Nagamune T. |
| Title | Selective expansion of genetically modified T cells using an antibody/interleukin-2 receptor chimera. |
| Journal | J Immunol Methods |
| Abstract |
Although adoptive transfer of tumor-specific T cells is a plausible approach for cancer immunotherapy, the therapeutic application was hampered due to severe side effects caused by administration of high-dose interleukin (IL)-2, which was used for long-lasting maintenance of tumor-specific T cells in vivo. To solve this problem, here we propose to use an antibody/IL-2 receptor chimera, which can transduce a growth signal in response to a cognate antigen. As a model system, V(H) or V(L) region of anti-hen egg lysozyme (HEL) antibody HyHEL-10 was tethered to extracellular D2 domain of erythropoietin receptor and transmembrane/cytoplasmic domains of IL-2 receptor beta or gamma chain. When the pairs of chimeric receptors (V(H)-IL-2Rbeta and V(L)-IL-2Rgamma, or V(H)-IL-2Rgamma and V(L)-IL-2Rbeta) were expressed in IL-3-dependent pro-B cell line Ba/F3 and IL-2-dependent T cell line CTLL-2, the cognate antigen HEL induced selective expansion of gene-modified cells in the absence of IL-3 and IL-2, respectively. Growth assay revealed that the combination of V(H)-IL-2Rbeta and V(L)-IL-2Rgamma transduced a more stringent HEL-dependent growth signal, indicating some conformational effects of the chimeras. Furthermore, STAT3, STAT5 and ERK1/2, which are hallmarks for IL-2R signaling, were all activated by the antibody/IL-2R chimeras. These results clearly demonstrate that the antibody/IL-2R chimeras could substantially mimic the wild-type IL-2R signaling, suggesting the potential application in expansion of gene-modified T cells. |
| Volume | 337(1) |
| Pages | 16-23 |
| Published | 2008-8-20 |
| DOI | 10.1016/j.jim.2008.05.003 |
| PII | S0022-1759(08)00166-X |
| PMID | 18589435 |
| MeSH | Animals Cell Line Cell Proliferation* Extracellular Signal-Regulated MAP Kinases / metabolism Humans Immunoglobulin Variable Region / genetics Immunoglobulin Variable Region / metabolism* Interleukin Receptor Common gamma Subunit / genetics Interleukin Receptor Common gamma Subunit / metabolism* Interleukin-2 / metabolism Interleukin-2 Receptor beta Subunit / genetics Interleukin-2 Receptor beta Subunit / metabolism* Interleukin-3 / metabolism Lymphocyte Activation* Mice Muramidase / immunology* Receptors, Erythropoietin / genetics Receptors, Erythropoietin / metabolism Recombinant Fusion Proteins / metabolism STAT3 Transcription Factor STAT5 Transcription Factor / metabolism Signal Transduction / immunology T-Lymphocytes / enzymology T-Lymphocytes / immunology* Time Factors Transfection |
| IF | 1.901 |
| Times Cited | 11 |
| WOS Category | BIOCHEMICAL RESEARCH METHODS IMMUNOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 21 |
| Altmetric score changes over past 6months | 3.0 |
| Resource | |
| DNA material | pIL-2R gamma 2 (RDB01201) |