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Severe Combined Immunodeficient Mice (severe + combined_immunodeficient_mouse)
Selected AbstractsIdentification of SPARC as a candidate target antigen for immunotherapy of various cancersINTERNATIONAL JOURNAL OF CANCER, Issue 6 2010Mitsuhiro Inoue Abstract To establish efficient anticancer immunotherary, it is important to identify tumor-associated antigens (TAAs) directing the immune system to attack cancer. A genome-wide cDNA microarray analysis identified that secreted protein acidic and rich in cysteine (SPARC) gene is overexpressed in the gastric, pancreatic and colorectal cancer tissues but not in their noncancerous counterparts. This study attempted to identify HLA-A24 (A*2402)-restricted and SPARC-derived CTL epitopes. We previously identified H-2Kd -restricted and SPARC-derived CTL epitope peptides in BALB/c mice, of which H-2Kd -binding peptide motif is comparable with that of HLA-A24 binding peptides. By using these peptides, we tried to induce HLA-A24 (A*2402)-restricted and SPARC-reactive human CTLs and demonstrated an antitumor immune response. The SPARC-A24-1143,151 (DYIGPCKYI) and SPARC-A24-4225,234 (MYIFPVHWQF) peptides-reactive CTLs were successfully induced from peripheral blood mononuclear cells by in vitro stimulation with these two peptides in HLA-A24 (A*2402) positive healthy donors and cancer patients, and these CTLs exhibited cytotoxicity specific to cancer cells expressing both SPARC and HLA-A24 (A*2402). Furthermore, the adoptive transfer of the SPARC-specific CTLs could inhibit the tumor growth in nonobese diabetic/severe combined immunodeficient mice bearing human cancer cells expressing both HLA-A24 (A*2402) and SPARC. These findings suggest that SPARC is a potentially useful target candidate for cancer immunotherapy. [source] Neuropathologic and neuroinflammatory activities of HIV-1-infected human astrocytes in murine brainGLIA, Issue 2 2006Huanyu Dou Abstract The balance between astrocyte and microglia neuroprotection and neurotoxicity defines the tempo of neuronal dysfunction during HIV-1-associated dementia (HAD). Astrocytes maintain brain homeostasis and respond actively to brain damage by providing functional and nutritive neuronal support. In HAD, low-level, continuous infection of astrocytes occurs, but the functional consequences of thisinfection are poorly understood. To this end, human fetal astrocytes (HFA) and monocyte-derived macrophages (MDM) were infected with HIV-1DJV and HIV-1NL4-3 (neurotropic and lymphotropic strains respectively) and a pseudotyped Vesicular Stomatitis Virus (VSV/HIV-1NL4-3) prior to intracranial injection into the basal ganglia of severe combined immunodeficient mice. Neuropathological and immunohistochemical comparisons for inflammatory and neurotoxic activities were performed amongst the infected cell types at 7 or 14 days. HIV-1-infected MDM induced significant increases in Mac-1, glial fibrillary acidic protein, ionized calcium-binding adapter molecule 1, and proinflammatory cytokine RNA and/or protein expression when compared with HSV/HIV-1- and HIV-1-infected HFA and sham-operated mice. Levels of neuron-specific nuclear protein, microtubule-associated protein 2, and neurofilament antigens were reduced significantly in the brain regions injected with human MDM infected with HIV-1DJV or VSV/HIV-1. We conclude that HIV-1 infection of astrocytes leads to limited neurodegeneration, underscoring the early and active role of macrophage-driven neurotoxicity in disease. © 2006 Wiley-Liss, Inc. [source] Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective immunity in inoculated host animalsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2005Masako Chiyo Abstract A novel cytokine interleukin-27 (IL-27), composed of p28 and Epstein-Barr virus-induced gene 3 (EBI3), is produced from activated dendritic cells and is involved in an early phase of T-helper type I differentiation. We examined whether Colon 26 murine colon carcinoma cells that were retrovirally transduced with the p28 -linked EBI3 gene (Colon 26/IL-27) could produce antitumor effects in inoculated mice. Although proliferation in vitro of Colon 26/IL-27 cells was not different from that of parent cells, syngeneic BALB/c mice rejected Colon 26/IL-27 tumors inoculated and subsequently acquired tumor-specific protective immunity. In contrast, mice inoculated with Colon 26 cells transduced with either the p28 or EBI3 gene developed tumors and survival of the mice remained the same as that of the mice inoculated with parent cells. Syngeneic nude mice developed Colon 26/IL-27 tumors, but the growth was retarded compared to that of parent tumors. Depletion of natural killer cells from nude mice with anti-asialo GM1 antibody diminished the growth retardation of Colon 26/IL-27 tumors. Survival of severe combined immunodeficient mice that received subcutaneous inoculation of Colon 26/IL-27 cells was not different from that of the immunodeficient mice inoculated with parent cells. Interferon-, was produced from CD4+ and CD8+ T, and natural killer cells of the mice that rejected Colon 26/IL-27 tumors and cytotoxic activity against Colon 26 cells were also detected from the mice. These data collectively suggest that expressed IL-27 in tumors produces T cell-dependent and-independent antitumor effects and is a possible therapeutic strategy for cancer. ©2005 Wiley-Liss, Inc. [source] Comparison of two in vivo models for prostate cancer: Orthotopic and intratesticular inoculation of LNCaP or PC-3 cellsINTERNATIONAL JOURNAL OF UROLOGY, Issue 12 2004KIYOSHI KOSHIDA Abstract, Background:, The critical events in the clinical course of prostate cancer are the occurrence of metastasis and the induction of the hormone-refractory status of the disease. In order to investigate the factors responsible for these events, we need appropriate in vivo models. Materials and methods:, Orthotopic and intratesticular models were created by the injection of LNCaP cells or PC-3 cells into the prostate or testis of severe combined immunodeficient mice. Results:, LNCaP cells in the intratesticular model showed a higher incidence of tumor formation and lymph node metastasis when compared with those in the orthotopic model, while PC-3 cells were highly tumorigenic and metastastic in both models. A high concentration of androgens might play a role in tumor aggressiveness of LNCaP cells, given that enhanced mRNA expressions of integrin ,V and vascular endothelial growth factor was induced by dehydrotestosterone administration in vitro. The high expression of metastasis-related genes, including the urokinase plasminogen activator system, metalloproteinases and vascular endothelial growth factor-C, might be attributed to the high metastatic potential in both models. Interestingly, testicular xenografts of LNCaP cells were able to survive on the subcutis back of castrated male mice as well female mice. Conclusions:, Intratesticular models of prostate cancer appear to be suitable for studying the mechanisms of metastasis and for evaluating various treatment strategies. [source] Efficient generation of respiratory syncytial virus (RSV)-neutralizing human MoAbs via human peripheral blood lymphocyte (hu-PBL)-SCID mice and scFv phage display librariesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2000H. Nguyen RSV is one of the major causes of pneumonia and bronchiolitis in infants and young children and is associated with high mortality. RSV neutralizing human antibody (hu-Ab) is known to mediate resistance to viral infection as well as to be an effective treatment for severe lower respiratory tract RSV infection. We have previously demonstrated that human primary and secondary immune responses can be established in severe combined immunodeficient mice engrafted with human peripheral blood lymphocytes (hu-PBL-SCID). By combining this animal model with the single-chain Fv antibody (scFv) phage display library technique, we were able to investigate further its clinical potential by generating a panel of human scFvs that exhibit both high F glycoprotein (RSV-F) binding affinities (,108 M,1) and strong neutralizing activities against RSV infection in vitro. Sequencing analysis of the randomly isolated anti-RSV-F scFv clones revealed that they were derived from different VH families with mutations in the complementarity-determining region 1 (CDR1). The results suggest that: (i) RSV-F-specific human immune responses and affinity maturation can be induced in hu-PBL-SCID mice; and (ii) this approach can be applied to generate large numbers of human scFvs with therapeutic potential. Despite the fact that hu-PBL-SCID mouse and human scFv phage display library have individually been established, our approach contributes a simple and significant step toward the generalization of antigen-specific human monoclonal antibody (hu-MoAb) production and their clinical applications. [source] | ||||||||||