AXL-Targeting Antibody-Drug Conjugate as Novel Therapy for Triple-Negative Breast Cancer

Abstract

We have identified AXL, a receptor protein tyrosine kinase (RTK), being highly expressed and activated(phosphorylated) in Triple Negative Breast Cancer. We have determined that AXL provides survival benefit to the tumor cells. We have also discovered a monoclonal antibody that is highly specific to AXL, and does not bind to other related receptor tyrosine kinases. We have also shown that the antibody internalizes and degrades the AXL receptor. We have humanized the antibody for clinical development. We have established high producer cell line and propagated in chemically defined medium. We thus propose to conduct the following studies using novel target and novel therapeutic. Specific aims are; Aim 1. To develop a humanized antibody-drug conjugate (ADC) that can effectively target the AXL membrane receptor tyrosine kinase. Aim 2. To test the efficacy of the AXL-targeted ADC in preclinical animal models Aim 3. To develop a mass spectrometry-based method to effectively monitor AXL expression and activation in xenograft tissues and clinical samples.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2021
Accession Number
AD1190952

Entities

People

  • Parkash Gill

Organizations

  • University of Southern California

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Antibodies
  • Biomedical Research
  • Breast Cancer
  • California
  • Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Cytotoxins
  • Department Of Defense
  • Gel Electrophoresis
  • Kinases
  • Mass Spectrometry
  • Membranes
  • Neoplasms
  • Professional Development
  • Proteins
  • Standards
  • Survival
  • Targeting
  • Targets
  • Therapy
  • Tissues
  • Tyrosine

Fields of Study

  • Biology
  • Medicine

Readers

  • Breast cancer cell signaling and growth regulation.
  • Oncology
  • Oncology and Biomarker-Based Cancer Detection.