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Victor Jeffrey Leyton

Professeur associé, Faculté de médecine et des sciences de la santé
FMSS Dép. médecine nucléaire et radiobiologie

Présentation

Sujet de recherche

Antibodies, Biological and Biochemical Mechanisms, Cancer Diagnosis and Detection, Cancer of the Urinary System, Development of Drug Delivery Systems, Leukemia

Disciplines de recherche

Biochemistry, Cell Biology, Chemistry, Molecular Biology, Physics

Mots-clés

Antibodies (functionalization - engineering), Antibody conjugation chemistry (cargo attachment), Endosome escape mechanism for antibodies, Intracellular trafficking control, Life science and health applications, Multidisciplinary (chemistry-biology-physics)

Intérêts de recherche

The antibody-conjugate field has made significant progress recently owing to careful optimization of several parameters, including drug potency, linker technology, and the stoichiometry and placement of conjugated drugs. However, these technological progresses have only marginally improved survival rates in humans with cancer. This is due to the current antibody-conjugates inability to overcome multiple cellular mechanisms that reduce drug cellular accumulation and leads to resistance. . We have discovered and patented a technology that functionalizes antibodies allowing them to overcome the mechanisms causing reduced drug accumulation. We apply this technology to improve the accumulation of radioisotope, photosensitizers, and chemotherapeutics to more accurately identify and kill cancer cells. Currently we focus on the targeting of leukemic stem cells and muscle invasive bladder cancer (MIBC) cells.

Centre de recherche

Centre de recherche du CHUS

Langues parlées et écrites

Anglais, Français, Espagnol (castillan)

Diplômes

(2013). (Post-doctorate, Pharmaceutical sciences). University of Toronto.

(2008). Engineered Antibody Fragments for the Targeting and Imaging of Prostate Stem Cell Antigen (PSCA)-Expressing Xenografts In Vivo by microPET (Doctorate, Molecular and Medical Pharmacology). University of California, Los Angeles.

(2002). Thermodynamic principles of protein folding (Bachelor's Honours, Biochemistry). University of California, Santa Barbara.

Prix et distinctions

  • (2016) Canada Graduate Scholarship (Frederick Banting and Charles Best) Mentor to MSc student (Andreanne Rondeau) who successfully attained this award. Canadian Institutes of Health Research. (Prize / Award).
  • (2013) American Association for Cancer Research (AACR) - Minority Scholar in Cancer Research Award - State-of-the Art Molecular Imaging in Cancer Biology and Therapy Supported by the National Cancer Institute (NCI). (Prize / Award).
  • (2011) American Society of Hematology (ASH) Annual Conference Travel Award. (Prize / Award).
  • (2008) 2008 UCLA In vivo cellular and molecular imaging center award. Most impactful research. University of California, Los Angeles. (Prize / Award).
  • FRSQ Junior 1 Bourse. Fonds de recherche du Québec - Santé (FRQS). (Prize / Award).

Publications

Articles de revue

  • Michel Paquette, Simon Beaudoin, Marc-Andre Bonin, Roger Lecomte, Brigitte Guerin, and Jeffrey V. Leyton. (2016). In vivo evaluation of an IL-5Ra-targeting, 64Cu-labeled,cholic acid-NLS antibody in a bladder cancer model by PET imaging (). Clinical Cancer Research (Submitted).
  • Samira Osati, Michel Paquette, Simon Beaudoin, Hasrat Ali, Brigitte Guerin, Jeffrey V. Leyton, and Johan E. van Lier. (2015). Preprint 3Multimodality BODIPY-Estradiol conjugates for tumor imaging (PET, Fluorescence) and photodynamic therapy: A "see and treat" approach (). Journal of Medicinal Chemistry (Submitted).
  • Jeffrey Leyton, Catherine Gao, Brent Williams, Armand Keating, and Raymond Reilly. (2015). A radiolabeled antibody targeting CD123+ leukemia stem cells – initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AMLspecimens. Leukemia Research Reports 18 (4), 55-59. (Published).
  • Simon Beaudoin, Andreanne Rondeau, Olivier Martel, Marc-Andre Bonin, Johannes van Lier, and Jeffrey V. Leyton. (2015). Preprint 1ChAcNLS, a novel modification to antibody-conjugates permitting target cell-specific endosomal escape and localization to thenucleus for enhancing total cellular accumulation (). Journal of Controlled Release (Submitted).
  • Dane Bergstrom, Jeffrey V. Leyton, Arman Zereshkian, Zhongli Cai, Conrad Chan, and Raymond M. Reilly. (2014). 111In-NLS-CSL360 – An Auger electron radioimmunotherapeutic agent for acute myeloid leukemia targeting the leukemic stem cell population. European Journal of Nuclear Medicine and Molecular Imaging (EJNMMI) 41 (Suppl. 2), 597. (Published).
  • Jeffrey V. Leyton, Brent Williams, Catherine Gao, Armand Keating, Mark Minden and Raymond M. Reilly. (2014). MicroSPECT/CT imaging of primary human AML expressing the CD123+/CD131- leukemia stem cell phenotype engrafted into the bone marrow and spleen of NOD/SCID mice using 111In-DTPA-NLS-CSL360 radioimmunoconjugates. Leukemia Research 38 (11), 1367-73. (Published).
  • Arman Zereshkian, Jeffrey V. Leyton, Zhongli Cai, Dane Bergstrom, Michael Weinfeld, and Raymond M. Reilly. (2014). The human polynucleotide kinase/phosphatase (hPNKP) inhibitor A12B4C3 radiosensitizes human myeloid leukemia cells to Auger electron-emitting anti-CD123 111In-NLS-7G3 radioimmunoconjugates. Nuclear Medicine & Biology 41 (5), 377-383. (Published).
  • Humphrey Fonge and Jeffrey V. Leyton. (2013). Positron emission tomographic imaging of iodine 124 anti-prostate stem cell antigen-engineered antibody fragments in LAPC-9 tumor-bearing severe combined immunodeficiency mice. Molecular imaging 12 (3), 191-202. (Published).
  • Jeffrey V. Leyton, Brent Williams, Armand Keating, John Dick, Mark Minden, and Raymond M. Reilly. (2013). 111In-CSL360 mAb modified with nuclear localization signal containing peptides specific for the leukemic stem cell phenotype CD123+CD131- for leukemia detection and Auger electron radioimmunotherapy. Journal of Nuclear Medicine and Molecular Imaging Special Edition (AACR/SNMMI State-of-the-Art Molecular Imaging in Cancer Biology and Therapy) doi:10.2967/jnm542abs (Published).
  • Brent Williams, Xing-Hua Wang, Sonam Maghera, Jeffrey V. Leyton, Raymond M. Reilly, and Armand Keating. (2012). Irradiated NK-92 targets AML leukemic stem cells in vivo and gene-modified CD16+NL-92 mediates antibody dependent cell mediated cytotoxicity (ADCC) against CD123+ cells. Blood 120 (21), 1909. (Published).
  • Jeffrey V. Leyton, Catherine Gao, John Dick, Mark Minden, and Raymond M. Reilly. (2012). Auger electron radioimmunotherapy of acute myelogenous leukemia using novel 111In-labeled chimeric mAb 360 reduces CD123+/CD131- leukemic stem cell population in NOD/SCID mice. European Journal of Nuclear Medicine and Molecular Imaging (EJNMMI) 39 (Suppl. 2), 717. (Published).
  • Aisha Fasih, Humphrey Fonge, Zhongli Cai, Jeffrey V. Leyton, Igor Tikhomirov, Susan J. Done, Raymond M. Reilly. (2012). 111In-Bn-DTPA-nimotuzumab with/without modification with nuclear translocation sequence (NLS) peptides: an Auger electron-emitting radioimmunotherapeutic agent for EGFR-positive and trastuzumab (Herceptin)-resistant breast cancer. Breast Cancer Research and Treatment 135 (1), 189-200. (Published).
  • Jeffrey V. Leyton, Meiduo Hu, Catherine Gao, Patricial V. Turner, John E. Dick JE, Mark Minden, and Raymond M. Reilly. (2011). Auger electron radioimmunotherapeutic agent specific for the CD123+/CD131- phenotype of the leukemia stem cell population. Journal of Nuclear Medicine and Molecular Imaging 52 (9), 1465-1473. (Published).
  • Catherine Gao, Jeffrey V. Leyton, Mark Minden, Aaron Schimmer, and Raymond M. Reilly. (2011). 111In-NLS-CSL360, an Auger electron-emitting radioimmunotherapeutic (RIT) agent specific for CD123+/CD131- leukemic stem cells (LSCs). Journal of Nuclear Medicine and Molecular Imaging 52 (Suppl. 1), 354. (Published).
  • Jeffrey V. Leyton, Catherine Gao, Meiduo Hu, John Dick, Mark Minden, and Raymond M. Reilly. (2010). MicroSPECT/CT imaging of human leukemia engraftment in NOD-scid mice using 111In-labeled 7G3 anti-CD123 antibodies. Blood 116 968. (Published).
  • Eric Lepin, Jeffrey V. Leyton, Y Zhou, Tove Olafsen, Felix Salazar, Katelyn McCabe, Scott Hahm, JD Marks, Robert E. Reiter, and Anna M. Wu. (2010). An affinity matured minibody for PET imaging of prostate stem cell antigen (PSCA)-expressing tumors. European Journal of Nuclear Medicine and Molecular Imaging (EJNMMI) 37 (8), 1529-38. (Published).
  • Jeffrey V. Leyton, Meiduo Hu, Mark Minden, Robert Sutherland, Jeffrey Brandwein, and Raymond M. Reilly. (2009). Targeted auger electron radiotherapy of acute myelogenous leukemia using novel 111In-labeled mAb 7G3, humanized mAb 360 and 360-F(ab′)2 antibody fragment towards the leukemic stem cell. European Journal of Nuclear Medicine and Molecular Imaging (EJNMMI) 36 (Suppl. 2), 255. (Published).
  • Jeffrey V. Leyton, Meiduo Hu, Mark Minden, Robert Sutherland, Jeffrey Brandwein, and Raymond M. Reilly. (2009). 111In-NLS-7G3, a novel auger electron-emitting radiotherapeutic targeting the leukemic stem cell epitope CD123. Journal of Nuclear Medicine and Molecular Imaging 50 (Suppl. 2), 570. (Published).
  • Jeffrey V. Leyton, Eric Lepin, Y Zhou, Jim Marks, Tove Olafson, Robert Reiter, James Tomlinson, and Anna M. Wu. (2009). MicroPET imaging of pancreatic xenografts expressing prostate stem cell antigen (PSCA) using I-124-labeled minibodies. Journal of Nuclear Medicine and Molecular Imaging 49 (Suppl. 1), 53. (Published).
  • Jeffrey V. Leyton, Tove Olafsen, Mark A. Sherman, Karl Bauer, Patrick Aghajanian, Robert E. Reiter, Anna M. Wu. (2009). Engineered humanized diabodies for microPET imaging of prostate stem cell antigen-expressing tumors. Protein Engineering Design & Selection 22 (3), (Published).
  • Jeffrey V. Leyton, Tove Olafsen, Eric Lepin, Scott Hahm, Karl Bauer, Robert E. Reiter, Anna M. Wu. (2008). Humanized radioiodinated minibody for imaging of prostate stem cell antigen-expressing tumors. Clinical Cancer Research 14 (22), (Published).
  • Sui G, Wang J, Lee CC, Lu W, Lee SP, Leyton JV, Wu AM, Tseng HR. (2008). Solution-phase surface modification in intact poly(dimethylsiloxane) microfluidic channels. Analytical Chemistry 78 (15), (Published).
  • Tove Olafsen, Z Gu, Mark A. Sherman, Jeffrey V. Leyton, ME Witkosky, John Shively, Andrew Raubitschek, Sherrie L. Morrison, Anna M. Wu, and Robert E. Reiter. (2008). Targeting, imaging, and therapy using a humanized antiprostate stem cell antigen (PSCA) antibody. Journal of Immunotherapy 30 (4), (Published).

Articles de conférence

  • Paquette, M., Lecomte, R., Guerin, B., Lopez, A., and Leyton, J.V. (2015). A novel antibody-conjugate design to exploit internalization and trafficking of interleukin-5 receptor alpha-subunit - implications for more effective tumor targeting. 2nd International Symposium of the Cancer Research Center of Lyon. (Accepted).
  • Leyton, J.V., Williams, B.A., Keating, A., Dick, J.E., Minden, M., and Reilly, R.M. (2013). 111In-CSL360 mAb modified with nuclear localization signal containing peptides specific for the leukemic stem cell phenotype CD123+CD131- for leukemia detection and Auger electron radioimmunotherapy. Society of Nuclear Medicine and Molecular Imaging, 41. (Published).
  • Williams, B.A., Wang, X-H., Maghera, S., Leyton, J.V., Reilly, R.M., and Keating, A. (2012). Irradiated NK-92 targets AML leukemic stem cells in vivo and gene-modified CD16+NK-92 mediates antibody dependent cell mediated cytotoxicity (ADCC) against CD123+ cells. Blood, #53435. (Published).
  • Leyton, J.V., Gao, C., Dick, J.E., Minden, M., and Reilly, R.M. (2012). Auger Electron Radioimmunotherapy of Acute Myelogenous Leukemia Using Novel 111In-labeled chimeric mAb 360 reduces CD123+CD131- leukemic stem cell population in NOD/SCID mice. European Journal of Nuclear Medicine and Molecular Imaging, OP717. (Published).
  • Gao, C., Leyton, J.V., Minden, M., Schimmer, A. and Reilly, R.M. (2011). 111In-NLS-CSL360, an Auger electron-emitting radioimmunotherapeutic (RIT) agent specific for CD123+/CD131- leukemic stem cells (LSCs). Society of Nuclear Medicine and Molecular Imaging, 2011;52:354. (Published).
  • Leyton, J.V., Gao, C., Hu, M., Dick, J.E., Minden, M.D. and Reilly, R.M. (2010). MicroSPECT/CT Imaging of Human Leukemia Engraftment in NOD-scid Mice Using 111In-labeled 7G3 anti-CD123 Antibodies. Blood, #968. (Published).
  • Leyton, J.V., Hu, M., Minden, M., Sutherland, R., Brandwein, j., and Reilly, R.M. (2009). Targeted Auger Electron Radiotherapy of Acute Myelogenous Leukemia Using Novel 111In-labeled mAb 7G3, humanized mAb 360 and 360-F(ab’)2 Antibody Fragment Towards the Leukemic Stem Cell. European Journal of Nuclear Medicine and Molecular Imaging, OP255. (Published).
  • Leyton, J.V., Hu, M., Minden, M., Sutherland, R., Brandwein, j., and Reilly, R.M. (2009). 111In-NLS-7G3, A novel auger electron-emitting radiotherapeutic targeting the leukemic stem cell epitope CD123. Society of Nuclear Medicine and Molecular Imaging, 2009;50:570. (Published).

Propriétés intellectuelles

Patents

  • ChAcNLS, a novel modification for enhanced cellular accumulation of payloads attached to immunoconjugates. (In Progress).

Autres contributions

Cours enseignés

  • Pharmaceutics (PHM 224Y). (2011-09-08).
  • Radiopharmaceutics (PHM 1115H). (2010-10-08).
  • Biotechnology and Biopharmaceuticals (PHM 224Y). (2010-09-24).
  • Radiopharmaceutics (PHM 1115H). (2008-11-13).

Gestion d'évènements

  • Founder. Biologie pour l'imagerie (Biology for Imaging) This is a monthly journal club celebrating the role of biology in molecular imaging. Each month a student/postdoctoral fellow presents an interesting biological mechanism that is being imaged. (Club).
  • Organizing committee member. Imaginez l'imagerie (Imagine Imaging) International Symposium Sherbrooke Molecular Imaging Centre. (Conference).

Présentations

  • (2015). Antibodies with Integrated endosome escape and multi-directional intracellular trafficking-control capabilities for molecular transport. Interdisciplinary Nanosciences Centre of Marseille (CINaM). Marseille
  • (2015). A novel antibody-conjugate design to exploit internalization and trafficking of interleukin-5 receptor alpha-subunit - implication for more effective tumor targeting. 2nd International Symposium of the Cancer Research Center of Lyon. Lyon
  • (2014). A Novel Delivery System for Enhanced Cellular Accumulation Inside IL-3Rα+ Leukemic Stem Cells Using Functionalized 7G3 Antibody. Imagine Imaging International Symposium on Molecular Imaging. Sherbrooke
  • (2014). Photodynamic Imaging of IL-5Rα+ Muscle Invasive Bladder Cancer. Imagine Imaging International Symposium on Molecular Imaging. Sherbrooke
  • (2014). Manipulation of receptor-mediated internalization of the leukemic stem cell marker IL-3Rα enhances intracellular transportation and stability of the immunoconjugate CANLS-7G3. Journée scientifique for the Cancer: Biology, Prognostic and Diagnostic Research Axis of the Research Centre/University Hospital Sherbrooke. Sherbrooke
  • (2013). Strategy for intracellular transport of 64Cu-labeled antibodies specific for IL-3R-alpha. Journée scientifique for the molecular imaging centre of Sherbrooke. Sherbrooke
  • (2013). 111In-CSL360 mAb modified with nuclear localization signal containing peptides specific for the leukemic stem cell phenotype CD123+CD131- for leukemia detection and Auger electron radioimmunotherapy. American Association for Cancer Research-Society of Nuclear Medicine and Molecular Imaging Joint Conference on State-of-the-Art Molecular Imaging in Cancer Biology and Therapy. San Diego