Leyton Victor Jeffrey

Professeur régulier
Département de médecine nucléaire et radiobiologie
Faculté de médecine et des sciences de la santé de l'Université de Sherbrooke


Courriel : Jeffrey.Leyton@USherbrooke.ca

Importance de la recherche

Targeted drug delivery

Antibody-conjugate (AC) is a catch-all term for a very powerful class of pharmaceutical. ACs are typically composed of a monoclonal antibody (mAb) conjugated to a molecular payload for providing increased diagnostic accuracy or effective therapy in humans. Their ability to target diseased cells with exquisite specificity contributes to the significant increases in life expectancy over standard chemotherapy in patients with cancer, albeit several months and not several years, which is desired. Nonetheless, this is an important impact on healthcare. Doctors now have additional options for cancers where ACs are available. Because there is a high public demand for these pharmaceuticals, ACs impact aspects of the economy as pharmaceutical companies are creating new divisions for these drugs and thus creating new jobs for the biotech workforce. The most recent (Nov. 12, 2015) market outlook just in canceer predicts this technology to reach approximately $12.7 Billion (worth $600 Million in 2014) by 2020. This means that although this technology is already proven in humans, it is still in its adolescence and about to hit a growth spurt.
The principal interest of my laboratory is to reinvent targeted chemotherapy for cancer with innovative technology advancements to ACs and apply them as more effective pharmaceuticals in cancer. In order for me to do this, I needed to position my research with a competitive edge. Chemotherapeutic-attached ACs commonly referred to as antibody-drug conjugates were introduced during the 1990s as a promising solution to deliver cancer cell-specific chemotherapy. This system harnesses mAb specificity to deliver the chemotherapeutic to the tumor to significantly localize its accumulation and thereby enhance its activity. To be effective, ACs target receptors undergoing cellular internalization into vesicles known as endosomes that are trafficked to lysosomes. Herein lies the problem. The current mechanistic center point for AC effectiveness is that inside the lysosome the acidic pH activates proteases that catabolize the AC and allows drug release and cellular accumulation. However, this process is plagued by cellular mechanisms that decrease the intracellular drug accumulation levels, which leads to effective but short-term cancer regression. Cancer cells eventually build resistance and patients ultimately die. The research in my laboratory is addressing these deficiencies by aiming to reinvent a more effective method of accumulating the delivered drug with ACs. My principal application for this next generation of ACs is in bladder cancer, a devastating cancer with major importance to Quebec and the Eastern Townships, increasing the importance of this technology I bring to the University.

Réalisations représentatives

  • American Association for Cancer Research (AACR) – Scholar in Cancer Research Award Recipient (2013)
  • Banting Research Foundation Discovery Award Recipient (2014)
  • Bourse FRQS chercheur boursier Junior 1 (2015)
  • Savoir-faire

  • Antibody-conjugate design for improved targeting
  • Mouse models of cancer using isolated cancer stem cells
  • Imaging and treatment of mice engrafted with primary cancer specimens
  • Developing attractive biomedical antibody-conjugate products for commercialization and with high translational potential
  • Publications

    • Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides for Increasing Cellular Accumulation and Improving Tumor Targeting.
      Type de publication : Article PubMed

      Date de parution : 2018-03-08
      Hyperlien :
    • NLS-Cholic Acid Conjugation to IL-5Rα-Specific Antibody Improves Cellular Accumulation and In Vivo Tumor-Targeting Properties in a Bladder Cancer Model.
      Type de publication : Article PubMed

      Date de parution : 2018-03-01
      Hyperlien : http://www.ncbi.nlm.nih.gov/pubmed/29433309
    • Targeting IL-5Rα with antibody-conjugates reveals a strategy for imaging and therapy for invasive bladder cancer.
      Type de publication : Article PubMed

      Date de parution : 2017-05-19
      Hyperlien : http://www.ncbi.nlm.nih.gov/pubmed/29123949
    • BODIPY-17α-ethynylestradiol conjugates: Synthesis, fluorescence properties and receptor binding affinities.
      Type de publication : Article PubMed

      Date de parution : 2016-12-25
      Hyperlien : http://www.ncbi.nlm.nih.gov/pubmed/28049591
    • Paradoxical effects of Auger electron-emitting (111)In-DTPA-NLS-CSL360 radioimmunoconjugates on hCD45(+) cells in the bone marrow and spleen of leukemia-engrafted NOD/SCID or NRG mice.
      Type de publication : Article de revue

      Date de parution : 2016-10-03
      Hyperlien : https://www.ncbi.nlm.nih.gov/pubmed/27497632
    • ChAcNLS-A14-B105, a novel fluorescence imaging agent for enhanced detection of muscle invasive bladder cancer
      Type de publication : Abstract

      Date de parution : 2016-09-01
      Hyperlien :