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#32741228   2020/08/01 To Up

In vivo gene therapy for canine SCID-X1 using cocal-pseudotyped lentiviral vector.

Hematopoietic stem and progenitor cell (HSPC)-based ex vivo gene therapy has demonstrated clinical success for X-linked severe combined immunodeficiency (SCID-X1) patients who lack a suitable donor for HSPC transplantation. Nevertheless, this form of treatment is associated with an increased risk of infectious disease complications and genotoxicity mainly due to the conditioning regimen. In addition, ex vivo gene therapy approaches require sophisticated facilities to manufacture gene-modified cells and to care for the patients after chemotherapy. Considering these impediments, we have developed an in vivo gene therapy approach to treat canine SCID-X1 after HSPC mobilization and systemic delivery of the therapeutic vector. Here, we investigated the use of the cocal envelope to pseudotype lentiviral vector (LV) expressing a functional gammaC gene. The cocal envelope is resistant to serum inactivation as compared to the commonly used vesicular stomatitis virus envelope glycoprotein (VSV-G) envelope and thus well suited for systemic delivery. Two SCID-X1 neonatal canines treated with this approach achieved long-term therapeutic immune-reconstitution with no prior conditioning. Therapeutic levels of gene-corrected CD3+ T-cells were demonstrated for at least 16 months, and all other correlates of T-cell functionality were within normal range. Retroviral integration site analysis demonstrated polyclonal T-cell reconstitution. Comparative analysis of integration profiles of foamy viral vector (FV) and cocal LV vector after in vivo gene therapy found distinct integration site patterns. These data demonstrate that clinically relevant and durable correction of canine SCID-X1 can be achieved with in vivo delivery of cocal LV. Since manufacturing of cocal LV is similar to VSV-G LV, this approach is easily translatable to a clinical setting thus provide for a highly portable and accessible gene therapy platform for SCID-X1.
Yogendra S Rajawat, Olivier Humbert, Savannah M Cook, Stefan Radtke, Dnyanada Pande, Mark Enstrom, Martin E Wohlfahrt, Hans-Peter Kiem

2073 related Products with: In vivo gene therapy for canine SCID-X1 using cocal-pseudotyped lentiviral vector.

250 mg5ug10 ug96 tests 100 G96 Samples

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#32737142   // To Up

Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141 dendritic cells to activate naïve and memory NY-ESO-1-specific CD8 T cells.

Dendritic cells (DCs) are crucial for the efficacy of cancer vaccines, but current vaccines do not harness the key cDC1 subtype required for effective CD8 T-cell-mediated tumor immune responses. Vaccine immunogenicity could be enhanced by specific delivery of immunogenic tumor antigens to CD141 DCs, the human cDC1 equivalent. CD141 DCs exclusively express the C-type-lectin-like receptor CLEC9A, which is important for the regulation of CD8 T cell responses. This study developed a new vaccine that harnesses a human anti-CLEC9A antibody to specifically deliver the immunogenic tumor antigen, NY-ESO-1 (New York esophageal squamous cell carcinoma 1), to human CD141 DCs. The ability of the CLEC9A-NY-ESO-1 antibody to activate NY-ESO-1-specific naïve and memory CD8 T cells was examined and compared with a vaccine comprised of a human DEC-205-NY-ESO-1 antibody that targets all human DCs.
Kelly-Anne Masterman, Oscar L Haigh, Kirsteen M Tullett, Ingrid M Leal-Rojas, Carina Walpole, Frances E Pearson, Jonathon Cebon, Christopher Schmidt, Liam O'Brien, Nikita Rosendahl, Ghazal Daraj, Irina Caminschi, Eric H Gschweng, Roger P Hollis, Donald B Kohn, Mireille H Lahoud, Kristen J Radford

2651 related Products with: Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141 dendritic cells to activate naïve and memory NY-ESO-1-specific CD8 T cells.

1 mg1.00 flask100 ug/vial100 extractions50 100 μg100 μg100 0.1 mg50 25 100 μg

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#32734203   2019/08/01 To Up

Proliferative Glomerulonephritis With Monoclonal IgG3λ Deposits: A Case Report of a Rare Cause of Monoclonal Gammopathy of Renal Significance.

Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits is a rare monoclonal gammopathy of renal significance with dense deposits on electron microscopy similar to polyclonal immune complex-mediated glomerulonephritis. 70% of patients with proliferative glomerulonephritis with monoclonal IgG are negative for a monoclonal (M) spike, and patients with this condition rarely develop an M spike during follow-up. We report a Chinese man in his 50s who presented with nephrotic syndrome and normal glomerular filtration rate. His first kidney biopsy showed masked IgG3 deposition, such that IgG3 staining was apparent only after digestion by enzyme on paraffin tissue, with a membranoproliferative pattern. During follow-up, his glomerular filtration rate worsened and proteinuria increased. 18 months after the first biopsy, the patient developed an M spike; a second kidney biopsy showed proliferative glomerulonephritis with monoclonal IgG deposits with unmasked IgG3λ deposition. The patient was successfully treated with bortezomib and dexamethasone, followed by lenalidomide and dexamethasone maintenance therapy.
Xiao-Juan Yu, Mang-Ju Wang, Zi-Hao Yong, Yi-Yi Ma, Su-Xia Wang, Fu-de Zhou, Ming-Hui Zhao

2133 related Products with: Proliferative Glomerulonephritis With Monoclonal IgG3λ Deposits: A Case Report of a Rare Cause of Monoclonal Gammopathy of Renal Significance.

100 ul100 ul100 ul100 ug100ug Lyophilized100 ul100.00 ug100.00 ug100ul100ug200 ug100ul

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#32734120   2020/05/16 To Up

Assessment of antigenic specificity of polyclonal antisera raised against by ELISA.

Lack of availability of commercial antibodies against whole-cell antigen or an antigenic epitope of () has hindered the development of novel immunoassays for the diagnose infectious coryza (IC). In this study, we raised polyclonal antisera against and evaluated its antigenic-specificity using enzyme linked immunosorbent assay (ELISA). We standardized antigen coating concentration(s), antibody detection limit, and optimal range of dilutions of primary antisera and secondary conjugated antibody. Our results show the development of antigen-specific antibody response in rabbits following repeated antigenic exposure with 0.5% formalinized antigen over a period of four weeks. Further, we showed its possible applicability in detection of pathogens in tissues by immunohistochemistry for confirmatory disease diagnosis and disease pathogenetic study.
Ajaz Ahmed, Sidhartha Deshmukh, Harmanjit Singh Banga, Sandeep Sodhi, Rajinder Singh Brar

1314 related Products with: Assessment of antigenic specificity of polyclonal antisera raised against by ELISA.

100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized96 wells (1 kit)100ug Lyophilized

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#32729057   2020/07/29 To Up

Direct detection of Strongyloides infection via molecular and antigen detection methods.

Laboratory diagnosis of Strongyloides infections can be grouped into direct and indirect detection methods, and a combination of the two methods is often needed to reach an accurate and timely diagnosis. This review focuses on non-conventional direct detection via molecular and antigen detection assays. Conventional PCR is the most commonly used molecular diagnostic for Strongyloides. Real-time PCR is accurate and highly sensitive for quantitative and qualitative analysis. Meanwhile, PCR-RFLP can efficiently distinguish human and dog isolates of S. stercoralis, S. fuelleborni (from monkey), and S. ratti (from rodent). Loop-mediated isothermal amplification (LAMP) amplifies DNA isothermally with high specificity, efficiency, and rapidity, and has potential for point-of-care (POC) translation. As for antigen detection assay, coproantigen detection ELISAs for strongyloidiasis traditionally relied on raising rabbit polyclonal antibodies against the parasite antigens for use as capture or detection reagents. Subsequently, hybridoma technology using animals has enabled the discovery of monoclonal antibodies specific to Strongyloides antigens and was utilised to develop antigen detection assays. In recent times, phage display technology has facilitated the discovery of scFv antibody against Strongyloides protein that can accelerate the development of such assays. Improvements in both direct detection methods are being made. Strongyloides molecular diagnostics is moving from the detection of a single infection to the simultaneous detection of soil-transmitted helminths. Meanwhile, antigen detection assays can also be multiplexed and aptamers can be used as antigen binders. In the near future, these two direct detection methods may be more widely used as diagnostic tools for strongyloidiasis.
Dinesh Balachandra, Hussain Ahmad, Norsyahida Arifin, Rahmah Noordin

1925 related Products with: Direct detection of Strongyloides infection via molecular and antigen detection methods.

100tests100tests96 tests100tests100tests100tests96 tests100 ug/vial100ug/vial100 assays96 tests

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#32728631   2020/05/27 To Up

Induction of synthesis of matrix metalloproteinases by interleukin-6; evidence for hepatic regeneration following hemi-hepatectomy.

Interleukin-6 (IL-6) can play a role in hepatic regeneration through many mechanisms, one of which is the induction of synthesis of matrix metalloproteinases (MMPs). The aim of the study is to focus on the significance and role of MMPs in the regenerative process to reveal the correlation between IL-6 and MMPs in rats following partial hepatectomy.
Thamer Alghamdi, Ihab Shafek Atta, Mohamed El-Refaei

1965 related Products with: Induction of synthesis of matrix metalloproteinases by interleukin-6; evidence for hepatic regeneration following hemi-hepatectomy.

5 G100 16-22 Sample Kit100 100ul500 96T100ul 0.1 mg 10

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#32728203   2020/07/29 To Up

Single-cell approaches to investigate B cells and antibodies in autoimmune neurological disorders.

Autoimmune neurological disorders, including neuromyelitis optica spectrum disorder, anti-N-methyl-D-aspartate receptor encephalitis, anti-MOG antibody-associated disorders, and myasthenia gravis, are clearly defined by the presence of autoantibodies against neurological antigens. Although these autoantibodies have been heavily studied for their biological activities, given the heterogeneity of polyclonal patient samples, the characteristics of a single antibody cannot be definitively assigned. This review details the findings of polyclonal serum and CSF studies and then explores the advances made by single-cell technologies to the field of antibody-mediated neurological disorders. High-resolution single-cell methods have revealed abnormalities in the tolerance mechanisms of several disorders and provided further insight into the B cells responsible for autoantibody production. Ultimately, several factors, including epitope specificity and binding affinity, finely regulate the pathogenic potential of an autoantibody, and a deeper appreciation of these factors may progress the development of targeted immunotherapies for patients.
Alicia Zou, Sudarshini Ramanathan, Russell C Dale, Fabienne Brilot

2725 related Products with: Single-cell approaches to investigate B cells and antibodies in autoimmune neurological disorders.

96 tests2 ml100 extractions50 mg100 μg100 μg100.00 ug100ml100.00 ug

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#32727914   // To Up

The safety and clinical effects of administering a multiantigen-targeted T cell therapy to patients with multiple myeloma.

Multiple myeloma (MM) is an almost always incurable malignancy of plasma cells. Despite the advent of new therapies, most patients eventually relapse or become treatment-refractory. Consequently, therapies with nonoverlapping mechanisms of action that are nontoxic and provide long-term benefit to patients with MM are greatly needed. To this end, we clinically tested an autologous multitumor-associated antigen (mTAA)-specific T cell product for the treatment of patients with high-risk, relapsed or refractory MM. In this study, we expanded polyclonal T cells from 23 patients with MM. T cells whose native T cell receptors were reactive toward five myeloma-expressed target TAAs (PRAME, SSX2, MAGEA4, Survivin, and NY-ESO-1) were enriched ex vivo. To date, we have administered escalating doses of these nonengineered mTAA-specific T cells (0.5 × 10 to 2 × 10 cells/m) to 21 patients with MM, 9 of whom were at high risk of relapse after a median of 3 lines of prior therapy and 12 with active, relapsed or refractory disease after a median of 3.5 prior lines. The cells were well tolerated, with only two transient, grade III infusion-related adverse events. Furthermore, patients with active relapsed or refractory myeloma enjoyed a longer than expected progression-free survival and responders included three patients who achieved objective responses concomitant with detection of functional TAA-reactive T cell clonotypes derived from the infused mTAA product.
Premal D Lulla, Ifigeneia Tzannou, Spyridoula Vasileiou, George Carrum, Carlos A Ramos, Rammurti Kamble, Tao Wang, Mengfen Wu, Mrinalini Bilgi, Adrian P Gee, Shivani Mukhi, Betty Chung, Linghua Wang, Ayumi Watanabe, Manik Kuvalekar, Mira Jeong, Yumei Li, Shamika Ketkar, Matthew French-Kim, Bambi Grilley, Malcolm K Brenner, Helen E Heslop, Juan F Vera, Ann M Leen

1075 related Products with: The safety and clinical effects of administering a multiantigen-targeted T cell therapy to patients with multiple myeloma.

100 extractions100 Tests1 kit

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