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ADC assessment

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As the new generation of immunotherapy, ADCs are meticulously constituted bio-macromolecules with high potential in the treatment of cancer and various other diseases. The information gathered from in vitro analysis provides a guideline for ADC optimization and the downstream in vivo ADC assessment. – PowerPoint PPT presentation

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Date added: 28 January 2019
Slides: 11
Provided by: BellaSmith2018

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Title: ADC assessment


1
ADC Assessment
2
Introduction
  • As the new generation of immunotherapy, ADCs are
    meticulously constituted bio-macromolecules with
    high potential in the treatment of cancer and
    various other diseases. The information gathered
    from in vitro analysis provides a guideline for
    ADC optimization and the downstream in vivo
    assessments.

3
ADC Assessment
4
Content
ADC in vitro Analysis
5
Biochemical analysis
  • analyze of the structure, stability, and drug
    conjugation pattern of the ADC.

6
Biochemical analysis
  • Structural Analysis evaluate antibody/antibody
    fragment structure to ensure its correct folding
    after conjugation.
  • ADC Stability Analysis ADC biochemical analysis
    that assess the physical stability (the tendency
    for auto-fragmentation and form aggregation,
    solubility, and thermal stability), chemical
    stability (minimum payload drug release at
    non-desired pH buffer systems, correct reactivity
    of the antibody during and after the conjugation
    process), in vitro serum stability (minimum
    payload drug release in serum)
  • Drug Antibody Ratio (DAR) Determination crucial
    steps in ADC biochemical analysis that assess the
    drug to antibody molar ratio and the distribution
    patter of different DAR species using advanced
    chromatography and mass spectroscopy analysis.
  • Conjugation Sites Analysis provide an accurate
    map of conjugated drug-linker locations via mass
    spectroscopy along with information regarding the
    physical attachment of the unreacted drug-linker
    on the antibody.

7
In vitro efficacy evaluation
  • using conventional antigen-bearing cultured cell
    lines to evaluate the behavior and cytotoxicity
    of an ADC

8
In vitro efficacy evaluation
  • ADC Affinity Evaluation determine and compare
    the antigen and Fc receptor binding affinity of
    ADC to non-conjugated antibody using approaches
    such as ELISA, flow cytometry, or surface plasmon
    resonance (SPR).
  • Internalization Assays the extent of ADC
    incorporation into the cells (internalization)
    upon binding is characterized in this stage of
    ADC in vitro efficacy analysis using ELISA or
    flow cytometry
  • Cytotoxicity Assays toxicity is measured by the
    cell viability upon the application of the ADC in
    a dosage-dependent manner using
    antigen-expressing cell lines.
  • ADCC and CDC Assays this set of ADC in vitro
    efficacy analysis measures the antibody dependent
    cellular cytotoxicity (ADCC) and complement
    dependent cytotoxicity (CDC) of the ADC to
    provide more detailed information regarding the
    pharmacological effects of the ADC.

9
3D in vitro
  • using highly innovated antigen-expressing 3D
    cultured cells to evaluate the behavior and
    cytotoxicity of an ADC for the mimicry of solid
    tumor treatment. 3D in vitro platform evaluates
    several ADC performance parameters.

10
3D in vitro
  • ADC Targeting Profile evaluate the targeting
    pattern, efficiency, and reflect target
    distribution in a 3D cultured cell clusters in
    mimicking of the internal environment of a solid
    tumor.
  • ADC Tumor Penetration break the barrier of
    single layers in the 2D cultured cells and
    provide a three-dimensional distribution profile
    of an ADC in solid tumors.
  • ADC Solid Tumor Efficacy demonstrate the
    efficacy of an ADC in a whole new regime and
    generate results more accurately resemble the
    scenarios of solid tumors.
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