Search results for: Mouse Anti-Insulin(1D4 ) Monoclonal Antibody, PE-Cy3 Conjugated
#32613835 2020/07/02 To Up
Systemic Delivery of Aptamer Conjugated XBP1 siRNA Nanoparticle for Efficient Suppression of HER2+ Breast Cancer.siRNA therapeutics as an emerging class of drug development is successfully coming to clinical utilization. RNA-based therapy is widely utilized to explore the mechanism and cure a variety of gene-specific diseases. Tumor is an oncogene-driven disease; many genes related to tumor progression and chemoresistance. Although human epidermal growth factor receptor 2 (HER2) targeted monoclonal antibody therapy has dramatically improved the survival rate, chemotherapy remains essential to in HER2 positive (HER2+) breast cancer patients. Recently, X-box-binding protein 1 (XBP1) has been involved in triple-negative breast cancer (TNBC) chemoresistance and progression, but its function in HER2+ breast cancer is poorly explored. Here, we silenced XBP1 expression by using RNase resistant RNA nanoparticles (NPs). Intravenous injections of RNA NPs with HER2 specific aptamers resulted in strongly bounding to tumors but not to healthy tissues. XBP1 deletion by RNA NPs impaired angiogenesis and inhibited cell proliferation, significantly suppressed breast cancer growth, and promoted the sensitization of chemotherapy in HER2+ breast cancer mouse model. Totally, these results reveal the function of XBP1 in HER2+ breast cancer development, chemoresistance and imply that targeting XBP1 by RNA NPs may offer an easy and promising strategy for the combination treatment of breast cancer in the future.
Long Zhang, Chaofeng Mu, Tinghong Zhang, Yingying Wang, Yili Wang, Luhui Fan, Cong Liu, Hao Chen, Jianliang Shen, Kun Wei, Huaqiong Li
2689 related Products with: Systemic Delivery of Aptamer Conjugated XBP1 siRNA Nanoparticle for Efficient Suppression of HER2+ Breast Cancer.96T100ul
#32523525 2020/05/25 To Up
Nanoliposomes as a Therapeutic Tool for Alzheimer's Disease.The accumulation of extracellular amyloid-beta (Aβ), denoted as senile plaques, and intracellular neurofibrillary tangles (formed by hyperphosphorylated Tau protein) in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). The current and most accepted hypothesis proposes that the oligomerization of Aβ peptides triggers the polymerization and accumulation of amyloid, which leads to the senile plaques. Several strategies have been reported to target Aβ oligomerization/polymerization. Since it is thought that Aβ levels in the brain and peripheral blood maintain equilibrium, it has been hypothesized that enhancing peripheral clearance (by shifting this equilibrium towards the blood) might reduce Aβ levels in the brain, known as the sink effect. This process has been reported to be effective, showing a reduction in Aβ burden in the brain as a consequence of the peripheral reduction of Aβ levels. Nanoparticles (NPs) may have difficulty crossing the blood-brain barrier (BBB), initially due to their size. It is not clear whether particles in the range of 50-100 nm should be able to cross the BBB without being specifically modified for it. Despite the size limitation of crossing the BBB, several NP derivatives may be proposed as therapeutic tools. The purpose of this review is to summarize some therapeutic approaches based on nanoliposomes using two complementary examples: First, unilamellar nanoliposomes containing Aβ generic ligands, such as sphingolipids, gangliosides or curcumin, or some sphingolipid bound to the binding domain of ApoE; and second, nanoliposomes containing monoclonal antibodies against Aβ. Following similar rationale NPs of poly(lactide-co-glycolide)-poly (ethylene glycol) conjugated with curcumin-derivate (PLGA-PEG-B6/Cur) were reported to improve the spatial learning and memory capability of APP/PS1 mice, compared with native curcumin treatment. Also, some new nanostructures such as exosomes have been proposed as a putative therapeutic and prevention strategies of AD. Although the unquestionable interest of this issue is beyond the scope of this review article. The potential mechanisms and significance of nanoliposome therapies for AD, which are still are in clinical trials, will be discussed.
Lara Ordóñez-Gutiérrez, Francisco Wandosell96 tests96 tests96 tests1,000 tests96 tests 100ul1000 assays100ul100 assays100 assays100μg
#32512615 2020/06/08 To Up
ELISA for the Detection of the Prohibited Doping Agent Higenamine.Higenamine is a natural benzyltetrahydroisoquinoline alkaloid produced by various plants. In the World Anti-Doping Agency report of 2020, higenamine is classified as a class S3 (selective and nonselective 2-agonist) prohibited substance. To minimize the problems resulting from the misuse of higenamine-containing products as well as from the abuse of doping agents in sport, numerous higenamine-detection methods have been investigated. In the present study, a monoclonal antibody against the ()-enantiomer of higenamine was successfully produced and applied in the indirect competitive ELISA to detect the content of ()-higenamine in plant samples and related products. By immunizing BALB/c mice with higenamine-BSA, the aforementioned monoclonal antibody was produced even when the hapten number, which was the higenamine molecules conjugated to the BSA molecule, was relatively low (approximately 4). The MAb was characterized and utilized in the established icELISA assay with a detectable range of 7.81 - 125 ng/mL. The assay limit of detection (LOD) was 4.41 ng/mL, indicating higher sensitivity than the conventional HPLC-UV methods. Various validation processes demonstrated that icELISA was precise, with the maximum CV (%) of the intra- and inter-assays of 11.58% and 10.18%, respectively. Moreover, the assay was accurate, with the recovery rates of spiked ()-higenamine ranging from 82% to 113%, and sufficiently reliable for the detection of ()-higenamine in various kinds of samples. Notably, the present study describes the first immunoassay for ()-higenamine.
Poomraphie Nuntawong, Hiroyuki Tanaka, Seiichi Sakamoto, Satoshi Morimoto 100 G196 Well11mg96 tests2000 IU100.00 ul500 Units
#32509182 2020/05/15 To Up
In vivo characterization of PD-L1 expression in breast cancer by immuno-PET with Zr-labeled avelumab.Programmed death protein 1 and programmed death-ligand 1 (PD-1/PD-L1) have been widely studied as one of the most critical immune check-point pairs in the cancer microenvironment. In breast cancer (BrCa), the expression of PD-L1 is regarded as a determinant biomarker for patient stratification and prediction of inhibition response. Quantitative positron emission tomography (PET) imaging of PD-L1 expression in tumors using a therapeutic antibody in the clinic seems to be a promising approach that can complement conventional histopathological methods and overcome several issues, such as the tumor heterogeneities, sampling representativeness and clear differentiation of positive and negative results. In this study, we synthesized and evaluated Zr-labeled avelumab (Ave) for the in vivo characterization of PD-L1 expression in BrCa. Confocal imaging of BrCa cells and flow cytometry were employed to evaluate PD-L1 expression in MDA-MB-231 cells. The intact human monoclonal antibody targeting PD-L1, i.e., Ave, was conjugated to p-SCN-Deferoxamine (Df) and labeled with Zr. After intravenous injection of Zr-Df-avelumab (Zr-Df-Ave), PET imaging of MDA-MB-231 tumor-bearing mice, with or without blocking, was performed. High PD-L1 expression of MDA-MB-231 cells was confirmed by in vitro immuno-fluorescent staining and flow cytometry. PET imaging indicated the peak uptake of Zr-Df-Ave in the tumor (6.4±1.0 %ID/g), spleen (10.2±0.7 %ID/g) and lymph nodes (6.9±1.0 %ID/g) at 48 h after injection (n=4). Blocking study using unlabeled Ave could reduce the tracer uptake in these tissues (5.2±1.0 %ID/g in the tumor, 4.9±0.5 %ID/g in the spleen and 5.8±1.1 %ID/g in lymph nodes at 48 h, n=4), which demonstrated the specificity of Zr-Df-Ave. Biodistribution study and immuno-fluorescent staining were consistent with the quantitative data from PET imaging. Herein, we offer the evidence supporting the value of immuno-PET imaging using Zr-Df-Ave for non-invasive characterization of PD-L1 expression in BrCa and the applicability of this tracer in BrCa for treatment evaluation after immunotherapy.
Miao Li, Emily B Ehlerding, Dawei Jiang, Todd E Barnhart, Weiyu Chen, Tianye Cao, Jonathan W Engle, Weibo Cai
1902 related Products with: In vivo characterization of PD-L1 expression in breast cancer by immuno-PET with Zr-labeled avelumab.
#32404408 2020/05/13 To Up
Preclinical characterization of an antibody-drug conjugate targeting CS-1 and the identification of uncharacterized populations of CS-1-positive cells.Multiple myeloma (MM) is a hematologic cancer that disrupts normal bone marrow function with multiple lines of therapeutic options but is incurable, as patients ultimately relapse. We developed a novel antibody-drug conjugate targeting CS-1, a protein that is highly expressed on MM tumor cells. The anti-CS-1 monoclonal antibody specifically bound to cells expressing CS-1 and, when conjugated to a cytotoxic pyrrolobenzodiazepine payload, reduced the viability of MM cell lines in vitro. In mouse models of MM, a single administration of the CS-1 ADC caused durable regressions in disseminated models and complete regression in a subcutaneous model. In an exploratory study in cynomolgus monkeys, the CS-1 ADC demonstrated a half-life of 3-6 days; however, no highest non-severely toxic dose was achieved, as bone marrow toxicity was dose limiting. Bone marrow from dosed monkeys showed reductions in progenitor cells as compared with normal marrow. In vitro cell killing assays demonstrated that the CS-1 ADC substantially reduced the number of progenitor cells in healthy bone marrow, leading us to identify previously unreported CS-1 expression on a small population of progenitor cells in the myeloid-erythroid lineage. This finding suggests that bone marrow toxicity is the result of both on-target and off-target killing by the ADC.
Ruoyan Chen, Saravanan Rajan, Michael G Overstreet, Elaine M Hurt, Suneetha B Thomas, Vanessa Muniz-Medina, Christopher Ward, Agnieszka Sadowska, Ryan Fleming, Subramanya Karanth, Shannon Breen, Bo Zheng, Yuling Wu, William O Iverson, Steven Novick, Terrence O'Day, Dipesha P Shah, Nazzareno Dimasi, Arnaud C Tiberghien, Jane Osbourn, Jill Walker
2742 related Products with: Preclinical characterization of an antibody-drug conjugate targeting CS-1 and the identification of uncharacterized populations of CS-1-positive cells.100ug100ug Lyophilized100ug100ug100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug100ug Lyophilized100ug100ug100ug Lyophilized
#32401486 2020/05/28 To Up
Aptamer-T Cell Targeted Therapy for Tumor Treatment Using Sugar Metabolism and Click Chemistry.The development of a tumor-targeted immunotherapy is highly required. The most advanced application is the use of CD19 chimeric antigen receptor (CAR)T (CAR-T) cells to B cell malignancies, but there are still side effects including potential carcinogenicity of lentiviral or retroviral insertion into the host cell genome. Here, we developed a nonviral aptamer-T cell targeted strategy for tumor therapy. Tumor cells surface-specific ssDNA aptamers were conjugated to CD3T cells (aptamer-T cells) using N-azidomannosamine (ManNAz) sugar metabolic cell labeling and click chemistry. We found that the aptamer-T cells could specifically target and bind to tumor cells (such as SGC-7901 gastric cancer cell and CT26 colon carcinoma cell) and in mice after adoptively transfer in. Aptamer-T cells led to significant regression in tumor volume due to being enriched at tumor microenvironment and producing strong cytotoxicity activities of CD3T cells with enhanced perforin, granzyme B, CD107a, CD69, and FasL expression. Moreover, aptamer-T displayed even stronger antitumor effects than an anti-PD1 immune-checkpoint monoclonal antibody (mAb) treatment in mice and combination with anti-PD1 yielded synergic antitumor effects. This study uncovers the strong potential of the adoptive nonviral aptamer-T cell strategy as a feasible and efficacious approach for tumor-targeted immunotherapy application.
Chuan-Gang Liu, Yong Wang, Peng Liu, Qi-Li Yao, Yuan-Yuan Zhou, Chao-Fan Li, Qiu Zhao, Guang-Hui Liu, Xiao-Lian Zhang
2613 related Products with: Aptamer-T Cell Targeted Therapy for Tumor Treatment Using Sugar Metabolism and Click Chemistry.96 tests1,000 tests
#32391516 2020/04/13 To Up
Rational design of peptides for identification of linear epitopes and generation of neutralizing monoclonal antibodies against DKK2 for cancer therapy.Dickkopf-related protein 2 (DKK2)is a member of the Dickkopf family in Wnt signaling pathway. Recently, we found that antibodies against DKK2 could activate natural killer (NK) and CD8+ T cells in tumors and inhibit tumor growth. In this paper, we report the rational design of peptides for identification of linear epitopes and generation of neutralizing monoclonal anti-DKK2 antibodies. To break the immune tolerance, we designed and chemically synthesized six peptides corresponding to different regions of DKK2 as immunogens and found five of them could generate mouse polyclonal antibodies that can bind to the active recombinant human DKK2 protein. Neutralizing mouse monoclonal antibodies (5F8 and 1A10) against human DKK2 were successfully developed by immunizing the mice with two different peptides (KLNSIKSSL and KVWKDATYS) conjugated to Keyhole limpet hemocyanin (KLH). The monoclonal antibodies not only abolish DKK2's suppression of Wnt signaling in vitro but also inhibits tumor growth in vivo. Currently, those two mAbs are undergoing humanization as immunotherapy candidates and may offer a new drug for treatment of human cancers.
Rongqing Zhao, Qian Xiao, Maohua Li, Wenlin Ren, Chenxi Xia, Xudong Liu, Yingzi Li, Tan Tan, Dianqing Wu, Le Sun
2891 related Products with: Rational design of peptides for identification of linear epitopes and generation of neutralizing monoclonal antibodies against DKK2 for cancer therapy.25 µg0.2 mg0.25 mg25 µg 5 G1 ml100 TESTS0.2 mg 1 G100.00 ug100.00 ug100 ug
#32368864 2020/05/05 To Up
Improved targeting of an anti-TAG-72 antibody drug conjugate for the treatment of ovarian cancer.Ovarian cancer has only a 17% 5-year survival rate in patients diagnosed with late stage disease. Tumor-associated glycoprotein-72 (TAG72), expressed in 88% of all stages of ovarian cancer, is an excellent candidate for antibody-targeted therapy, as it is not expressed in normal human adult tissues, except in the secretory endometrium.
Megan Minnix, Lin Li, Paul Yazaki, Junie Chea, Erasmus Poku, David Colcher, John E Shively
2153 related Products with: Improved targeting of an anti-TAG-72 antibody drug conjugate for the treatment of ovarian cancer.100ug Lyophilized100ug100ug100ug Lyophilized100ug Lyophilized100ug100ug100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug100ug Lyophilized
#32316186 2020/04/16 To Up
Near-Infrared Molecular Imaging of Glioblastoma by Miltuximab-IRDye800CW as a Potential Tool for Fluorescence-Guided Surgery.Glioblastoma (GBM) is one of the most aggressive tumors and its 5-year survival is approximately 5%. Fluorescence-guided surgery (FGS) improves the extent of resection and leads to better prognosis. Molecular near-infrared (NIR) imaging appears to outperform conventional FGS, however, novel molecular targets need to be identified in GBM. Proteoglycan glypican-1 (GPC-1) is believed to be such a target as it is highly expressed in GBM and is associated with poor prognosis. We hypothesize that an anti-GPC-1 antibody, Miltuximab, conjugated with the NIR dye, IRDye800CW (IR800), can specifically accumulate in a GBM xenograft and provide high-contrast in vivo fluorescent imaging in rodents following systemic administration. Miltuximab was conjugated with IR800 and intravenously administered to BALB/c nude mice bearing a subcutaneous U-87 GBM hind leg xenograft. Specific accumulation of Miltuximab-IR800 in subcutaneous xenograft tumor was detected 24 h later using an in vivo fluorescence imager. The conjugate did not cause any adverse events in mice and caused strong fluorescence of the tumor with tumor-to-background ratio (TBR) reaching 10.1 ± 2.8. The average TBR over the 10-day period was 5.8 ± 0.6 in mice injected with Miltuximab-IR800 versus 2.4 ± 0.1 for the control group injected with IgG-IR800 ( = 0.001). Ex vivo assessment of Miltuximab-IR800 biodistribution confirmed its highly specific accumulation in the tumor. The results of this study confirm that Miltuximab-IR800 holds promise for intraoperative fluorescence molecular imaging of GBM and warrants further studies.
Dmitry M Polikarpov, Douglas H Campbell, Lucinda S McRobb, Jiehua Wu, Maria E Lund, Yanling Lu, Sergey M Deyev, Andrew S Davidson, Bradley J Walsh, Andrei V Zvyagin, David A Gillatt
1982 related Products with: Near-Infrared Molecular Imaging of Glioblastoma by Miltuximab-IRDye800CW as a Potential Tool for Fluorescence-Guided Surgery.100 plates10 plates1 kit1 kit1 kit100 plates10 plates1 kit1 kit1 kit1 kit1 kit
#32302507 2020/04/17 To Up
Molecular Characterization and Experimental Utility of Monoclonal Antibodies with Specificity for Aliphatic Di- and Polyisocyanates.Aliphatic di- and polyisocyanates are crucial chemical ingredients in many industrial processes and are a well-recognized cause of occupational asthma. Serologic detection of "chemical epitopes" in biological samples could serve as an exposure surveillance approach toward disease prevention, and thus we sought to generate aliphatic isocyanate-specific monoclonal antibodies (mAbs). Three hybridomas were generated from Balb/c mice immunized with a commercial product containing a combination of uretdione, homopolymer, and monomeric forms of hexamethylene diisocyanate (HDI). Three stable hybridomas were subcloned by limiting dilution, two secreting IgG1κ and one secreting IgMκ mAb that bind aliphatic di- and polyisocyanates (conjugated to albumin), but not aromatic toluene or methylene diphenyl diisocyanate (TDI or MDI). Each mAb demonstrates slight differences in epitope specificity, for example, recognition of hydrogenated MDI (HMDI) or different carrier proteins (transferrin, actin) reacted with vapor phase HDI, and is encoded by unique recombination of different germline antibody genes, with distinct complementary determining regions. By western blot, all three mAbs detect a molecule with characteristics of an albumin adduct uniquely in urine from mice skin exposed to a mixture of aliphatic di- and polyisocyanate. Together, the data define molecular determinants of humoral immune recognition of aliphatic di- and polyisocyanates through new mAbs, which will serve as useful research reagents and may be applicable to future exposure surveillance efforts.
Adam V Wisnewski, Jian Liu
2118 related Products with: Molecular Characterization and Experimental Utility of Monoclonal Antibodies with Specificity for Aliphatic Di- and Polyisocyanates.1000 TESTS/0.65ml0.1 mg25 µg1 ml100 TESTS1 ml0.2 mg0.2 mg25 µg0.25 mg200ug100.00 ug
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