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Inhibition of Cdk Activity02:34

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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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Mitigation of Blood Borne Cell Attachment to Metal Implants through CD47-Derived Peptide Immobilization
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Macrophage checkpoint blockade: results from initial clinical trials, binding analyses, and CD47-SIRPα

AbdelAziz R Jalil1,2, Jason C Andrechak2,3, Dennis E Discher2,3

  • 1Department of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.

Antibody Therapeutics
|May 19, 2020
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The CD47-SIRPα macrophage checkpoint interaction is a cancer therapy target. Combination therapies, particularly anti-CD47 with rituximab, show promise against lymphomas.

Keywords:
CD47SIRPαimmune checkpointphagocytosis

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Area of Science:

  • Immunology
  • Cancer Biology
  • Drug Development

Background:

  • The CD47-SIRPα axis is an anti-phagocytic checkpoint involving macrophages and various cell types, including cancer cells.
  • Antibodies targeting CD47 or SIRPα are in development as cancer therapeutics.

Purpose of the Study:

  • To review clinical trials and preclinical data on CD47 blockade in cancer therapy.
  • To examine the interaction and structural features of CD47-SIRPα.

Main Methods:

  • Review of preclinical and clinical trial data.
  • Analysis of CD47-SIRPα interaction and structural characteristics.

Main Results:

  • CD47 blockade as monotherapy shows limited efficacy in human trials, except for specific lymphomas.
  • Preclinical studies in mouse models suggest efficacy, but these models may be less representative of human tumors.
  • Combination therapy of anti-CD47 with rituximab demonstrates efficacy in human lymphoma trials.

Conclusions:

  • The CD47-SIRPα checkpoint is a viable target, especially in combination therapies.
  • Combination strategies, like anti-CD47 with rituximab, hold significant promise for treating hematological malignancies such as lymphoma.