Biotech News: CD47 Antibody treatment shrinks or eliminates human cancer tumors

Nanoparticles, CD47, Stanford University, @TheLabWorld


Artificial protein fragment could allow nanobeads to transport drugs where they're needed. A group of US researchers have discovered that small man-made peptides can help to sneak drug-bearing nanobeads past the ever-vigilant immune system. 
To work successfully, drugs and imaging agents need to get to the diseased cells or tumors where they’re needed most. Although researchers are developing nanoparticles that help to deliver drugs to the right place, all therapeutic molecules face a deadly foe — the immune system. Its macrophages are intended to spot any intruding molecules in the blood and destroy them in a process called phagocytosis.

Researchers at the University of Pennsylvania in Philadelphia have now found a way to stop macrophages from destroying drug-bearing nanoparticles. They’ve designed and made a small segment of a crucial membrane protein called CD47, which is recognized by macrophages as being safe. Which means that molecules that contain CD47 can get past macrophages and into blood cells.  Similar Stanford University studies have shown comparable results, see video below. Biophysicist Dennis Discher, who led the work, says that he was inspired when he saw another group's work describing the structure of CD47. “I saw a minimal part of CD47 we could take out and make,” he says. This was the part of CD47 that attaches to a macrophage receptor protein, allowing the macrophage to let the protein, and its cargo, into the cell the macrophage is guarding. The work of Discher and his team is published today in Science.

Through the barricades

Using computer simulations to make sure that the CD47 fragment was folded correctly and was stable, the group designed and made a 21-amino-acid peptide based on the fragment. They then stuck the peptide to commercially available polystyrene nanobeads. The beads also carried a dye (or fluorophores) that showed up under fluorescence spectroscopy. The beads were injected into mice along with the same amount of other beads tagged with a different color fluorophores but not the peptide. After half an hour, the mouse blood had four times as many beads with the peptide fragment than the other bead, showing that many more of the peptide-tagged beads had got past the macrophage defense. The team then looked at mice with tumors and saw that the peptide-tagged, fluorescent nanobeads accumulated in the tumors. Nanoparticles tend to accumulate in tumors because of the tumor’s haphazard structure and leaky blood vessels. The nanoparticles spill through these blood vessels and get stuck in the tumor.

Buoyed by the evidence that the peptide-carrying nanobeads were circulating in the blood, Discher and his team also tagged their nanobeads with the anticancer drug paclitaxel. They saw that their peptide-carrying system shrank tumors just as well as the standard paclitaxel carrier, Cremophor, but without that carrier's toxic side effects. Neil Barclay of the University of Oxford, UK, was part of the team that worked out the CD47 structure that inspired Discher’s work. “It’s neat,” he says of Discher’s research. “It’s a new way of trying to get the immune system to prevent phagocytosis of drugs or particles.” Discher hopes that the system can be improved with custom-made nanobeads, rather than being limited to the off-the-shelf ones he and his team used. “We want to make this accessible and reproducible,” he says.

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    Mettler XS1003S | Analytical Scale
  • PTC-200, PTC-220, Opticon 2, qPCR, Real Time PCR, RTPCR
    MJ Research | PTC-200 | PCR Machine
  • Promega TD20/20 Luminometer, Turner TD20/20, Luminescence Spectrophotometer, Spectrometer
    Promega TD20/20 | Luminometer
  • ABI 3730xl DNA Sequencer, Used 3730xl, Capillary DNA Sequencer, Genetic Analyzer, Genetic Sequencer, TheLabWorldGroup
    ABI 3730xl | Used Genetic Analyzer
  • Lab Ice Maker, Scotsman AFE400
    Scotsman AFE400A | Lab Ice Maker
  • Roche GS 454 FLX+, Capillary Sequencer, base pairs, amplicon sequencing, whole genome sequencing, metagenomics, used DNA sequencer
    Roche GS 454 FLX+ | 2012 | DNA Sequencer
  • Roche GS Junior, Next Generation Sequencing, DNA Sequencer, GS De Novo Assembler
    Roche GS Junior | 2010 | DNA Sequencer
  • Agilent 1100, HPLC, Used Agilent 1100
    Agilent 1100 | HPLC System w/ G1315B & G1321A
  • Nikon TMS Inverted Phase Contrast Microscope use in biological laboratories to examine slides
    Nikon TMS Phase Contrast Microscope
  • Eppendorf 5418 Centrifuge, Eppendorf 5418, Eppendorf Microcentrifuge, Microfuge, Table top centrifuge, fixed angle rotor centrifuge
    Eppendorf 5418 Micro Centrifuge
  • GE Biacore S51, Label Free Assay, Biacore T100, Biacore 3000, Kinetic Analyzer, Protein Analyzer, Binding Reactions, in-vitro ADME, kinetic characterization
    GE Biacore S51 | SPR Analyzer
  • Agilent G1600AX, 3D CE Electrophoresis HPLC, Liquid Chromatograph, Capillary Electrophoresis, TheLabWorldGroup
    Agilent G1600AX | 3D CE Capillary Electrophoresis HPLC
  • Beckman Vi-Cell XR, Cell Counter, Size of Cell, Cell Size, Cell Viability, Viability, Cell Concentration, how to count cells, LabWorldGroup, TheLabWorldGroup
    Beckman Coulter Vi-Cell XR | 2009 Cell Viability Analyzer
  • BioRad ProteOn XPR36, Surface Plasmon Resonance, Protein Binding Machine, Kinetics of Protein, Affinity Determination, Used SPR, Biacore T200, T100, GE Biacore, @TheLabWorld
    BioRad ProteOn XPR36 | Protein Binding (SPR)
  • GE Biacore 2000, Binding Kinetic Analyzer, Label-Free Assay, Affinity Determination, Surface Plasmon, @TheLabWorld
    GE Biacore 2000 | SPR Analyzer
  • GE Biacore 3000, Surface Plasmon Resonance, Kinetic Analyzer, Protein Binding Analyzer, MALDI MS interface, Affinity Detection, Transient Binders, Method Development, Biacore, TheLabWorldGroup, Used Biacores
    Biacore 3000 | Surface Plasmon Analyzer
  • Labconco Cold Trap, Refrigerated Vapor Trap, Speed Vac System, Glass Trap, Aqueous Applications, Used Lab Equipment, The LabWorld Group
    Labconco CentriVap | Cold Trap | Speed Vac Unit
  • Labconco CentriVap Concentrator, aqueous, aqueous solution, aqueous chemistry, speed vac, Savant Speed Vac, Cold Trap, TheLabWorldGroup
    Labconco CentriVap | Concentrator | Aqueous System
  • Chromatography Column, BioChromatography, Pilot Scale, Drug Production, Drug Discovery, Production Columns, Pilot Purification
    Millipore Vantage A2 | 60 x 500 | Column
  • 3/4, channels, vortex, blower/motor, safety, added, interlock, velocity, high, work, clear, window, glass, area, view, Thermo 1286, Forma 1186, BioSafety Cabinet, Baker SG600, TheLabWorldGroup
    Thermo | Forma 1186 | Class II | A2 BioSafety Cabinet
  • SpectraMax Plus 384, TheLabWorldGroup, Spectrometer, Immunoassays, Elisa, elisa assay, microplate readers, Molecular Devices, path length
    Molecular Devices SpectraMax Plus 384 | UV/Vis Microplate Reader
  • Qiagen PSQ96, PSQ96A Pyrosequencer, used DNA Sequencer, Used Genetic Sequencer, PyroSequencing,dna sequence, dna replication, human genome project
    Qiagen PSQ96 | Pyrosequencer | Genetic Sequencer
  • Vistek Isolation Table, Vistek Vibration Table, Vistek Vibration Isolation Table, Isolation table, vibration table
    Vistek Vibration Isolation Table
  • GE Typhoon 9410 | Microarray Imager | Used Lab Equipment For Sale
  • Amersham 8600
  • Amersham Storm 860 | Imager
  • ABI 3100 | DNA Sequencer
  • ABI 3130xl | Genetic Analyzer