
Binding mechanisms of therapeutic antibodies to human CD20
Monoclonal antibodies (mAbs) focusing on human antigen CD20 (cluster of differentiation 20) represent vital immunotherapies for the therapy of B cell malignancies and autoimmune ailments. Sort I and II therapeutic mAbs differ in B cell binding properties and cytotoxic results, reflecting differential interplay mechanisms with CD20. Right here we current 3.7- to 4.7-angstrom cryo-electron microscopy constructions of full-length CD20 in complexes with prototypical sort I rituximab and ofatumumab and kind II obinutuzumab.
The constructions and binding thermodynamics show that upon binding to CD20, sort II mAbs type terminal complexes that preclude recruitment of further mAbs and complement parts, whereas sort I complexes act as molecular seeds to extend mAb native focus for environment friendly complement activation. Amongst sort I mAbs, ofatumumab complexes show optimum geometry for complement recruitment. The uncovered mechanisms ought to assist rational design of next-generation immunotherapies focusing on CD20.
Rational Design of a Sturdy Antibody-Like Small Molecule Inhibitor Nanoplatform for Enhanced Photoimmunotherapy
Immune checkpoint blockade of programmed cell death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pathway through antibody is a potent technique for T cells transforming. Nonetheless, the efficiency of antibody is partly compromised by its excessive worth, instability, threat of autoimmune illness, and many others. Small molecule inhibitors are attention-grabbing alternate options to antibodies.
Nonetheless, tumor-specific supply of small molecule inhibitor to the goal web site for reinforcing the interruption of PD-L1/PD-1 pathway isn’t reported. Herein, we designed a tumor-specific supply nanoplatform that would effectively ship the small molecule inhibitor to the exact goal web site, significantly enhancing the blocking impact of PD-L1/PD-1 pathway. Hyaluronic acid (HA) was conjugated with chlorin e6 (Ce6), leading to a HA-Ce6 conjugate (HC).
The nanoplatform was constructed by the HC micelles with encapsulation of small molecule inhibitor BMS 202 (BMS) to type BMS/HC micelles. The goal property of HA, mixed with the hyaluronidase-induced degradation of HA in tumor web site, permits the as-prepared micelles with tumor-specific supply of BMS for blocking PD-L1/PD-1 pathway.
Cooperative therapy with the photosensitizer Ce6, the current therapeutic nanoplatform demonstrated glorious photoimmunotherapy for tumor regression in distant tumors and lung metastasis. This technique of tumor-specific supply of small molecule inhibitors gives an efficient pathway to strengthen the blocking efficacy of PD-L1/PD-1 on efficient photoimmunotherapy.

controlpeptidecomprimary-antibodies
anti- IL-4 antibody |
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FNab04278 | FN Test | 100µg | EUR 702 |
Description: Antibody raised against IL-4 |
anti- IL-4 antibody |
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FNab04279 | FN Test | 100µg | EUR 702 |
Description: Antibody raised against IL-4 |
anti- IL-4 antibody |
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LSMab09861 | Lifescience Market | 100 ug | EUR 463.2 |
Anti-IL-4 antibody |
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PAab04278 | Lifescience Market | 100 ug | EUR 494.4 |
Anti-IL-4 antibody |
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STJ96510 | St John's Laboratory | 200 µl | EUR 236.4 |
Description: Rabbit polyclonal to IL-4. |
Anti-IL-4 antibody |
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STJ93699 | St John's Laboratory | 200 µl | EUR 236.4 |
Description: Rabbit polyclonal to IL-4. |
Anti-IL-4 antibody |
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STJ93700 | St John's Laboratory | 200 µl | EUR 236.4 |
Description: Rabbit polyclonal to IL-4. |
Human Interleukin-4 (IL-4) |
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1-CSB-EP011659HU | Cusabio |
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Description: Recombinant Human Interleukin-4(IL-4) expressed in E.coli |
IL-4, Interleukin-4, human |
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RC212-15 | Bio Basic | 5ug | EUR 125.26 |
mAb mouse anti-human IL-4 |
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CT253 | U-CyTech | 0.5 mg | EUR 312 |
rec IL-4 (human) |
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H-9630.0002 | Bachem | 2.0µg | EUR 313.2 |
rec IL-4 (human) |
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H-9630.0010 | Bachem | 10.0µg | EUR 1140 |
Human IL-4 Protein |
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abx060798-20ug | Abbexa | 20 ug | EUR 560.4 |
Anti-mouse IL-4 antibody |
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STJ15100035 | St John's Laboratory | 250 µg | EUR 403.2 |
Description: This monoclonal antibody enables sensitive and specific detection of mouse IL-4 in immunoassays such as ELISA and ELISpot. |
Anti-mouse IL-4 antibody |
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STJ15100036 | St John's Laboratory | 500 µg | EUR 632.4 |
Description: This monoclonal antibody is recommended for neutralization of mouse IL-4 bioactivity. |
Anti-mouse IL-4 antibody |
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STJ15100037 | St John's Laboratory | 250 µg | EUR 440.4 |
Description: This monoclonal antibody enables sensitive and specific detection of mouse IL-4 in immunoassays such as ELISA and ELISpot. |
Anti-IL-4 alpha antibody |
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STJ97665 | St John's Laboratory | 200 µl | EUR 236.4 |
Description: Rabbit polyclonal to IL-4Ralpha. |
Anti-IL-4 alpha antibody |
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STJ93702 | St John's Laboratory | 200 µl | EUR 236.4 |
Description: Rabbit polyclonal to IL-4Ralpha. |
Anti-IL-4 alpha antibody |
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STJ93703 | St John's Laboratory | 200 µl | EUR 236.4 |
Description: Rabbit polyclonal to IL-4Ralpha. |
IL-4, human recombinant |
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4137-10 | Biovision | each | EUR 333.6 |
IL-4, human recombinant |
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4137-1000 | Biovision | each | EUR 4444.8 |
IL-4, human recombinant |
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4137-50 | Biovision | each | EUR 836.4 |
Recombinant Human IL-4 |
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P0052 | FN Test | 100ug | EUR 626.83 |
Description: Recombinant Human protein for IL-4 |
Recombinant Human IL-4 |
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SJB02-03 | Amyotop | 10µg/vial | EUR 342 |
Recombinant Human IL-4 |
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SJB02-05 | Amyotop | 100µg/vial | EUR 864 |
Recombinant Human IL-4 |
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SJB02-06 | Amyotop | 30µg/vial | EUR 516 |
Recombinant Human IL-4 |
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HEILP-0401 | Cyagen | 5ug | Ask for price |
Human IL-4 ELISA antibody pair |
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CT742-10 | U-CyTech | 10-plate | EUR 656.4 |
Human IL-4 ELISA antibody pair |
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CT742-20 | U-CyTech | 20-plate | EUR 1118.4 |
Human Interleukin-4 (IL-4) Antibody (Biotin Conjugate) |
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32184-05121 | AssayPro | 150 ug | EUR 442.8 |
Human IL-4 ELISPOT antibody pair |
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CT642-10 | U-CyTech | 10-plate | EUR 633.6 |
Human IL-4 ELISPOT antibody pair |
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CT642-20 | U-CyTech | 20-plate | EUR 1107.6 |
pAb rabbit anti-human IL-4 receptor |
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CT248 | U-CyTech | 0.5 mg | EUR 220.8 |
Human High Sensitive Interleukin IL-4,IL-4 ELISA Kit |
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YLA4123HU-48T | Shanghai YL Biotech | 48T | EUR 435 |
Human High Sensitive Interleukin IL-4,IL-4 ELISA Kit |
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YLA4123HU-96T | Shanghai YL Biotech | 96T | EUR 562.5 |
Recombinant Human Interleukin-4/IL-4 (Human Cells) |
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CX03-10ug | Novoprotein | 10ug | EUR 175.2 |
Description: Lyophilized from a 0.2 μm filtered solution of 20mM PB, 150mM NaCl, pH 7.4. |
Recombinant Human Interleukin-4/IL-4 (Human Cells) |
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CX03-1mg | Novoprotein | 1mg | EUR 2739.6 |
Description: Lyophilized from a 0.2 μm filtered solution of 20mM PB, 150mM NaCl, pH 7.4. |
Recombinant Human Interleukin-4/IL-4 (Human Cells) |
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CX03-500ug | Novoprotein | 500ug | EUR 1935.6 |
Description: Lyophilized from a 0.2 μm filtered solution of 20mM PB, 150mM NaCl, pH 7.4. |
Recombinant Human Interleukin-4/IL-4 (Human Cells) |
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CX03-50ug | Novoprotein | 50ug | EUR 406.8 |
Description: Lyophilized from a 0.2 μm filtered solution of 20mM PB, 150mM NaCl, pH 7.4. |
human IL-4, His tag |
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E410A04-100 | EnoGene | 100μg | EUR 1152 |
Human Interleukin 4 (IL-4) CLIA Kit |
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abx195899-96tests | Abbexa | 96 tests | EUR 990 |
Human IL-4 ELISA kit |
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CT203A | U-CyTech | 5-plate | EUR 554.4 |
Human IL-4 ELISA kit |
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LF-EK50141 | Abfrontier | 1×96T | EUR 777.6 |
IL-4 ELISA KIT|Human |
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EF000163 | Lifescience Market | 96 Tests | EUR 826.8 |
IL-4 (Human) ELISA Kit |
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K4164-100 | Biovision | each | EUR 874.8 |
Human IL-4 ELISA Kit |
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RK00003 | Abclonal | 96 Tests | EUR 625.2 |
Human Interleukin 4,IL-4 ELISA KIT |
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201-12-0093 | SunredBio | 96 tests | EUR 528 |
Description: A quantitative ELISA kit for measuring Human in samples from biological fluids. |
Human Interleukin 4, IL-4 ELISA KIT |
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CSB-E04633h-24T | Cusabio | 1 plate of 24 wells | EUR 198 |
Description: Quantitativesandwich ELISA kit for measuring Human Interleukin 4, IL-4 in samples from serum, tissue homogenates, cell culture supernates, saliva. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price. |
Human Interleukin 4, IL-4 ELISA KIT |
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1-CSB-E04633h | Cusabio |
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Description: Quantitativesandwich ELISA kit for measuring Human Interleukin 4, IL-4 in samples from serum, tissue homogenates, cell culture supernates, saliva. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits. |
Human Interleukin 4,IL-4 ELISA KIT |
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CN-03206H1 | ChemNorm | 96T | EUR 520.8 |
Human Interleukin 4,IL-4 ELISA KIT |
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CN-03206H2 | ChemNorm | 48T | EUR 340.8 |
Human Interleukin 4(IL-4)ELISA Kit |
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GA-E0132HM-48T | GenAsia Biotech | 48T | EUR 346.8 |
Human Interleukin 4(IL-4)ELISA Kit |
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GA-E0132HM-96T | GenAsia Biotech | 96T | EUR 559.2 |
Human IL-4(Interleukin 4) ELISA Kit |
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EH0199 | FN Test | 96T | EUR 571.5 |
Description: Method of detection: Double Antibody, Sandwich ELISA;Reacts with: Homo sapiens;Sensitivity: 18.75pg/ml |
Human Interleukin 4(IL-4)ELISA Kit |
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QY-E04267 | Qayee Biotechnology | 96T | EUR 433.2 |
Human Interleukin 4,IL-4 ELISA Kit |
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YLA1519HU-48T | Shanghai YL Biotech | 48T | EUR 435 |
Human Interleukin 4,IL-4 ELISA Kit |
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YLA1519HU-96T | Shanghai YL Biotech | 96T | EUR 562.5 |
Human Interleukin-4 (IL-4) ELISA Kit |
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LF-EK60025 | Abfrontier | 1×96T | EUR 948 |
Human IL-4 ELISPOT kit |
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CT232-PB2 | U-CyTech | 2-plate | EUR 498 |
Human IL-4 ELISPOT kit |
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CT232-PB5 | U-CyTech | 5-plate | EUR 681.6 |
Human IL-4 ELISPOT kit |
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CT232-PR2 | U-CyTech | 2-plate | EUR 498 |
Human IL-4 ELISPOT kit |
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CT232-PR5 | U-CyTech | 5-plate | EUR 667.2 |
Human IL-4 ELISPOT kit |
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CT232-T2 | U-CyTech | 2-plate | EUR 432 |
Human IL-4 ELISPOT kit |
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CT232-T5 | U-CyTech | 5-plate | EUR 694.8 |
IL-4 (CHO-expressed), Human |
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HY-P7042 | MedChemExpress | 50ug | EUR 666 |
Recombinant Human Interleukin-4 (rHu IL-4) |
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AK9839-0010 | Akron Biotech | 10ug | EUR 780 |
Recombinant Human Interleukin-4 (rHu IL-4) |
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AK9839-0030 | Akron Biotech | 30ug | EUR 1356 |
Recombinant Human Interleukin-4 (rHu IL-4) |
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AK9839-0100 | Akron Biotech | 100ug | EUR 2040 |
GMP Recombinant Human Interleukin-4 (IL-4) |
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GMPhuIL-4-50ug | Gentaur Genprice | 50ug | EUR 528 |
Recombinant Human IL-4 Protein |
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PROTP05112-5 | BosterBio | 15ug | EUR 380.4 |
Description: IL-4 is a pleiotropic cytokine that regulates diverse T and B cell responses including cell proliferation, survival and gene expression. Produced by mast cells, T cells and bone marrow stromal cells, IL-4 regulates the differentiation of naive CD4+ T cells into helper Th2 cells, characterized by their cytokine-secretion profile that includes secretion of IL-4, IL-5, IL-6, IL-10, and IL-13, which favor a humoral immune response. Another dominant function of IL-4 is the regulation of immunoglobulin class switching to the IgG1 and IgE isotypes. Excessive IL-4 production by Th2 cells has been associated with elevated IgE production and allergy. Recombinant human IL-4 is a 15.1 kDa globular protein containing 130 amino acid residues. |
Recombinant Human IL-4 Protein |
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RP00995 | Abclonal | 5 μg | EUR 163.2 |
Human IL-4 Recombinant Protein |
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R00230-5 | BosterBio | 5ug/vial | EUR 310.8 |
Description: IL-4 has many biological roles, including the stimulation of activated B-cell and T-cell proliferation, and the differentiation of CD4+ T-cells into Th2 cells. It is a key regulator in humoral and adaptive immunity. Human IL-4 Recombinant Protein is purified interleukin-4 produced in yeast. |
Human Interleukin-4 (IL-4) AssayLite Antibody (RPE Conjugate) |
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32184-05151 | AssayPro | 150 ug | EUR 513.6 |
Human Interleukin-4 (IL-4) AssayLite Antibody (APC Conjugate) |
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32184-05161 | AssayPro | 150 ug | EUR 513.6 |
IL-4 Interleukin-4 Human Recombinant Protein |
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PROTP05112-1 | BosterBio | Regular: 20ug | EUR 380.4 |
Description: Interleukin-4 Human Recombinant produced in E.Coli is a single, non-glycosylated polypeptide chain containing 130 amino acids and having a molecular mass of 15kDa. ;The IL-4 is purified by proprietary chromatographic techniques. |
Human Interleukin-4 (IL-4) AssayLite Antibody (FITC Conjugate) |
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32184-05141 | AssayPro | 150 ug | EUR 513.6 |
Human CellExp? IL-4, Human Recombinant |
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6463-10 | Biovision | each | EUR 477.6 |
Human CellExp? IL-4, Human Recombinant |
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6463-50 | Biovision | each | EUR 1677.6 |
Human Interleukin-4 (IL-4) AssayLite Antibody (PerCP Conjugate) |
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32184-05171 | AssayPro | 150 ug | EUR 565.2 |
mAb mouse anti-rat IL-4 |
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CT028 | U-CyTech | 0.5 mg | EUR 312 |
mAb mouse anti-rat IL-4 |
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CT029 | U-CyTech | 0.5 mg | EUR 312 |
mAb rat anti-mouse IL-4 |
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CT324 | U-CyTech | 0.5 mg | EUR 312 |
mAb rat anti-mouse IL-4 |
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CT337 | U-CyTech | 0.5 mg | EUR 312 |
pAb rabbit anti-rat IL-4 |
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CT058 | U-CyTech | 0.5 mg | EUR 220.8 |
mAb mouse anti-monkey IL-4 |
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CT103 | U-CyTech | 0.5 mg | EUR 312 |
IL-4 antigen |
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E6IE600107 | EnoGene | 20ug | EUR 411.6 |
IL-4 antigen |
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E6L00107 | EnoGene | 20ug | EUR 458.4 |
IL-4 Antibody |
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5137-200 | Biovision | each | EUR 444 |
IL-4 Antibody |
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5137-30T | Biovision | each | EUR 175.2 |
IL-4 Antibody |
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F49086-0.08ML | NSJ Bioreagents | 0.08 ml | EUR 140.25 |
Description: IL4 is a pleiotropic cytokine produced by activated T cells. This cytokine is a ligand for interleukin 4 receptor. The interleukin 4 receptor also binds to IL13, which may contribute to many overlapping functions of this cytokine and IL13. STAT6, a signal transducer and activator of transcription, has been shown to play a central role in mediating the immune regulatory signal of this cytokine. This gene, IL3, IL5, IL13, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL13. This gene, IL13 and IL5 are found to be regulated coordinately by several long-range regulatory elements in an over 120 kilobase range on the chromosome. |
IL-4 Antibody |
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F49086-0.4ML | NSJ Bioreagents | 0.4 ml | EUR 322.15 |
Description: IL4 is a pleiotropic cytokine produced by activated T cells. This cytokine is a ligand for interleukin 4 receptor. The interleukin 4 receptor also binds to IL13, which may contribute to many overlapping functions of this cytokine and IL13. STAT6, a signal transducer and activator of transcription, has been shown to play a central role in mediating the immune regulatory signal of this cytokine. This gene, IL3, IL5, IL13, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL13. This gene, IL13 and IL5 are found to be regulated coordinately by several long-range regulatory elements in an over 120 kilobase range on the chromosome. |
IL-4 antibody |
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PAab09861 | Lifescience Market | 100 ug | EUR 463.2 |
IL-4 Antibody |
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RQ4162 | NSJ Bioreagents | 100 ug | EUR 356.15 |
Description: Interleukin-4 (IL-4), also known as a B-cell stimulatory factor1 (BSF1), is an immunomodulatory cytokine, which can inhibit the growth of tumour cells.1 The human cDNA contains a single open reading frame encoding a protein of 153 amino acids, including a putative signal peptide. IL-4 may act as an autocrine growth factor in pancreatic cancer cells and also give rise to the possibility that cancer-derived IL-4 may suppress cancer-directed immunosurveillance in vivo in addition to its growth-promoting effects, thereby facilitating pancreatic tumor growth and metastasis. The mouse and human genes and their protein products show structural and functional similarities. |
IL-4 Antibody |
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R30605 | NSJ Bioreagents | 100 ug | EUR 356.15 |
Description: Interleukin-4, also knowns as a B-cell stimulatory factor 1 (BSF1), is an immunomodulatory cytokine, which can inhibit the growth of tumour cells. The human cDNA contains a single open reading frame encoding a protein of 153 amino acids, including a putative signal peptide. It may act as an autocrine growth factor in pancreatic cancer cells and also give rise to the possibility that cancer-derived IL-4 may suppress cancer-directed immunosurveillance in vivo, in addition to its growth-promoting effects, thereby facilitating pancreatic tumor growth and metastasis. The mouse and human genes and their protein products show structural and functional similarities. The human gene, which occurs as a single copy in the haploid genome, is mapped on chromosome 5.2 |
IL-4 Antibody |
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R30841 | NSJ Bioreagents | 100 ug | EUR 356.15 |
Description: Interleukin-4, also knowns as a B-cell stimulatory factor 1 (BSF1), is an immunomodulatory cytokine, which can inhibit the growth of tumour cells. The human cDNA contains a single open reading frame encoding a protein of 153 amino acids, including a putative signal peptide. IL-4 may act as an autocrine growth factor in pancreatic cancer cells and also give rise to the possibility that cancer-derived IL-4 may suppress cancer-directed immunosurveillance in vivo in addition to its growth-promoting effects, thereby facilitating pancreatic tumor growth and metastasis. The mouse and human genes and their protein products show structural and functional similarities. The human gene, which occurs as a single copy in the haploid genome, is mapped on chromosome 5. |
Preclinical Antitumor Exercise and Biodistribution of a Novel Anti-GCC Antibody-Drug Conjugate in Affected person-Derived Xenografts
Guanylyl cyclase C (GCC) is a novel therapeutic goal with expression restricted to the apical facet of epithelial cell tight junctions regarded as solely accessible by intravenously administered brokers on malignant tissues the place GCC expression is aberrant.
- Within the current examine, we sought to judge the therapeutic potential of a second-generation investigational ADC, TAK-164, comprised of a human anti-GCC monoclonal antibody conjugated through a peptide linker to the extremely cytotoxic DNA alkylator, DGN549. The in vitro binding, payload launch, and in vitro exercise of TAK-164 was characterised motivating in vivo analysis.
- The efficacy of TAK-164 and the connection to publicity, pharmacodynamic marker activation, and biodistribution was evaluated in xenograft fashions and first human tumor xenograft (PHTX) fashions. We show TAK-164 selectively binds to, is internalized by, and has potent cytotoxic results towards GCC-expressing cells in vitro.
- A single intravenous administration of TAK-164 (0.76 mg/kg) resulted in vital progress charge inhibition in PHTX fashions of mCRC. Moreover, imaging research characterised TAK-164 uptake and exercise and confirmed constructive relationships between GCC expression and tumor uptake which correlated with antitumor exercise.
- Collectively, our information counsel that TAK-164 is very energetic in a number of GCC constructive tumors together with these refractory to TAK-264, a GCC-targeted auristatin ADC. A powerful relationship between uptake of 89Zr-labeled TAK-164, ranges of GCC expression and, most notably, response to TAK-164 remedy in GCC expressing xenografts and PHTX fashions.
- These information supported the scientific growth of TAK-164 as a part of a first-in-human scientific trial (NCT03449030).