Simultaneous Ligand-Directed Cytotoxic Toxin and Endosome Disruptor Delivery to Ablate Prostate Cancer

Abstract

In this grant we proposed to develop toxins that targeted GnRH-R and endosome disruptors that targeted bombesin 2 receptors to treat prostate cancer. In this first year, we have made GnRH-Gelonin and GnRH-Saporin conjugates. We have also established that GnRH-Gelonin and GnRH-Saporin conjugates induce apoptosis in a metastatic human prostate cancer cell lines(PC-3). We have further shown that targeting the endosome disruptor, listeriolysin O (LLO),to PC-3 cells using the kisspeptin receptor agonist (metastin) induces apoptosis. Metastin targeted LLO increases apoptosis induced by GnRH-Gelonin and/or GnRH-Saporin conjugates. We have developed a 2-step FPLC based purification for a his-tagged LLO that includes hydrophobic interaction chromatography followed by nickel affinity chromatography.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2018
Accession Number
AD1063938

Entities

People

  • Benjamin Renquist

Organizations

  • University of Alabama

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Biomedical Research
  • Cell Line
  • Cells
  • Chemistry
  • Chromatography
  • Culture Techniques
  • Cultured Cells
  • Endosomes
  • Health Care
  • Health Services
  • Medical Personnel
  • Molecules
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Solid Phases
  • Students
  • Targeting
  • Targets
  • Technology Transfer
  • Therapy
  • Universities

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Neurotoxicology
  • Prostate Cancer Biology.