Leslie Khawli

Professor Of Clinical Pathology

Director of the Pathology Graduate Program

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Overview

Dr. Leslie Khawli is a member of the faculty at the Keck School of Medicine of USC and currently the Director of the Pathology Graduate Program. Dr. Khawli holds a bachelor’s degree in biology from the American University of Beirut, Lebanon and a PhD in bioorganic chemistry from the University of Southern California, Los Angeles. After completing a NIH postdoctoral research fellowship in experimental nuclear medicine at Harvard Medical School in Boston, he joined the faculty at USC and has achieved the status of full professor. Dr. Khawli successfully made a transition to the biotechnology industry and joined Genentech/Roche in San Francisco to lead a wide range of research scientists in the practical application of his research and skills. After 8 years, he made a switch back to USC so he could translate his real-industrial drug development experience into an academic role.
Dr. Khawli active research has been revolved around the interface of chemistry and biology, specifically in the design, characterization and delivery of antibody, ADC, fusion protein, and cell-based therapeutics. A major research focus is to increase the value of mechanistic pharmacology of targeted biotherapeutics and investigate the structural and functional properties affecting their pharmacokinetics, biodistribution and metabolism, while ensuring safety and efficacy. His laboratory works effectively with Dr. Alan Epstein and many other interdisciplinary teams at USC to support the preclinical development of biotherapeutics that translate to clinical applications. These joint collaborative efforts have been supported by research agencies, private foundations, and numerous pharmaceutical companies. Dr. Khawli research has been reported in more than 100 peer-reviewed publications as well as book chapters and review articles. His research discoveries have resulted in several US and international patents pertaining to the targeted delivery of biotherapeutics. He is an accomplished scientist in his field and has been actively participating in various biotechnology companies in the US and abroad as a scientific consultant.
Dr. Khawli has had a long-standing commitment to various education and administrative programs aimed at mentoring and training graduate students and young researchers for careers in academia or biotech and pharma industry. He is also the recipient of numerous teaching, research and service awards.

Publications

  • Enhancing brain entry and therapeutic activity of chimeric antigen receptor T cells with intra-arterial NEO100 in a mouse model of CNS lymphoma J Neurosurg. 2023 Dec 29; 1-9. . View in PubMed
  • Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives Int J Mol Sci. 2021 Jun 16; 22(12). . View in PubMed
  • Advances in Immuno-PET for the Detection of Cancer and Assessment of Response to Therapy Curr Med Chem. 2021; 28(4):647-672. . View in PubMed
  • Spatio-temporal biodistribution of 89Zr-oxine labeled huLym-1-A-BB3z-CAR T-cells by PET imaging in a preclinical tumor model Sci Rep. 2021 07 23; 11(1):15077. . View in PubMed
  • Principles of N-Linked Glycosylation Variations of IgG-Based Therapeutics: Pharmacokinetic and Functional Considerations Antibodies (Basel). 2020 Jun 10; 9(2). . View in PubMed
  • A Humanized Lym-1 CAR with Novel DAP10/DAP12 Signaling Domains Demonstrates Reduced Tonic Signaling and Increased Antitumor Activity in B-Cell Lymphoma Models Clin Cancer Res. 2020 07 15; 26(14):3694-3706. . View in PubMed
  • Biodistribution and efficacy of an anti-TENB2 antibody-drug conjugate in a patient-derived model of prostate cancer Oncotarget. 2019 Oct 22; 10(58):6234-6244. . View in PubMed
  • Lym-1 Chimeric Antigen Receptor T Cells Exhibit Potent Anti-Tumor Effects against B-Cell Lymphoma Int J Mol Sci. 2017 Dec 20; 18(12). . View in PubMed
  • Systemic delivery of chTNT-3/CpG immunoconjugates for immunotherapy in murine solid tumor models Cancer Immunol Immunother. 2016 May; 65(5):511-23. . View in PubMed
  • Key factors influencing ADME properties of therapeutic proteins: A need for ADME characterization in drug discovery and development MAbs. 2016; 8(2):229-45. . View in PubMed
  • Recent Advances in Assessing Immunogenicity of Therapeutic Proteins: Impact on Biotherapeutic Development J Immunol Res. 2016; 2016:8141269. . View in PubMed
  • Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins J Immunol Res. 2016; 2016:2342187. . View in PubMed
  • Evaluating the Use of Antibody Variable Region (Fv) Charge as a Risk Assessment Tool for Predicting Typical Cynomolgus Monkey Pharmacokinetics J Biol Chem. 2015 Dec 11; 290(50):29732-41. . View in PubMed
  • A novel in vitro method to model the fate of subcutaneously administered biopharmaceuticals and associated formulation components J Control Release. 2015 Sep 28; 214:94-102. . View in PubMed
  • Comparative physiology of mice and rats: radiometric measurement of vascular parameters in rodent tissues Mol Pharm. 2014 May 05; 11(5):1591-8. . View in PubMed
  • Quantitative cumulative biodistribution of antibodies in mice: effect of modulating binding affinity to the neonatal Fc receptor MAbs. 2014 May-Jun; 6(3):689-96. . View in PubMed
  • Dose dependent pharmacokinetics, tissue distribution, and anti-tumor efficacy of a humanized monoclonal antibody against DLL4 in mice MAbs. 2014; 6(6):1631-7. . View in PubMed
  • Enhanced tumor retention of a radiohalogen label for site-specific modification of antibodies J Med Chem. 2013 Dec 12; 56(23):9418-26. . View in PubMed
  • Cytoreductive chemotherapy improves the biodistribution of antibodies directed against tumor necrosis in murine solid tumor models Mol Cancer Ther. 2013 Dec; 12(12):2827-36. . View in PubMed
  • Vascular physiology and protein disposition in a preclinical model of neurodegeneration Mol Pharm. 2013 May 06; 10(5):1514-21. . View in PubMed
  • Drug delivery across the blood-brain barrier Mol Pharm. 2013 May 06; 10(5):1471-2. . View in PubMed
  • Generation of tumor-targeted antibody-CpG conjugates J Immunol Methods. 2013 Mar 29; 389(1-2):45-51. . View in PubMed
  • Characterization of therapeutic monoclonal antibodies reveals differences between in vitro and in vivo time-course studies Pharm Res. 2013 Jan; 30(1):167-78. . View in PubMed
  • An integrated approach to identify normal tissue expression of targets for antibody-drug conjugates: case study of TENB2 Br J Pharmacol. 2013 Jan; 168(2):445-57. . View in PubMed
  • Differential effects of predosing on tumor and tissue uptake of an 111In-labeled anti-TENB2 antibody-drug conjugate J Nucl Med. 2012 Sep; 53(9):1454-61. . View in PubMed
  • Physiochemical and biochemical factors influencing the pharmacokinetics of antibody therapeutics AAPS J. 2012 Sep; 14(3):554-8. . View in PubMed
  • Compartmental tissue distribution of antibody therapeutics: experimental approaches and interpretations AAPS J. 2012 Sep; 14(3):612-8. . View in PubMed
  • Maximizing tumour exposure to anti-neuropilin-1 antibody requires saturation of non-tumour tissue antigenic sinks in mice Br J Pharmacol. 2012 May; 166(1):368-77. . View in PubMed
  • Pharmacokinetics and toxicology of therapeutic proteins: Advances and challenges World J Biol Chem. 2012 Apr 26; 3(4):73-92. . View in PubMed
  • Effects of anti-VEGF on pharmacokinetics, biodistribution, and tumor penetration of trastuzumab in a preclinical breast cancer model Mol Cancer Ther. 2012 Mar; 11(3):752-62. . View in PubMed
  • Minipig as a potential translatable model for monoclonal antibody pharmacokinetics after intravenous and subcutaneous administration MAbs. 2012 Mar-Apr; 4(2):243-55. . View in PubMed
  • Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates Nat Biotechnol. 2012 Jan 22; 30(2):184-9. . View in PubMed
  • Impact of drug conjugation on pharmacokinetics and tissue distribution of anti-STEAP1 antibody-drug conjugates in rats Bioconjug Chem. 2011 Oct 19; 22(10):1994-2004. . View in PubMed
  • Antibody delivery of drugs and radionuclides: factors influencing clinical pharmacology Ther Deliv. 2011 Jun; 2(6):769-91. . View in PubMed
  • Effects of anti-VEGF on predicted antibody biodistribution: roles of vascular volume, interstitial volume, and blood flow PLoS One. 2011 Mar 15; 6(3):e17874. . View in PubMed
  • Effects of charge on antibody tissue distribution and pharmacokinetics Bioconjug Chem. 2010 Dec 15; 21(12):2153-63. . View in PubMed
  • Effect of immune complex formation on the distribution of a novel antibody to the ovarian tumor antigen CA125 Drug Metab Dispos. 2010 Dec; 38(12):2309-19. . View in PubMed
  • Charge variants in IgG1: Isolation, characterization, in vitro binding properties and pharmacokinetics in rats MAbs. 2010 Nov-Dec; 2(6):613-24. . View in PubMed
  • Development and evaluation of a novel method for preclinical measurement of tissue vascular volume Mol Pharm. 2010 Oct 04; 7(5):1848-57. . View in PubMed
  • Fc-mOX40L fusion protein produces complete remission and enhanced survival in 2 murine tumor models J Immunother. 2008 Apr; 31(3):235-45. . View in PubMed
  • Construction and preclinical characterization of Fc-mGITRL for the immunotherapy of cancer Clin Cancer Res. 2008 Jan 15; 14(2):579-88. . View in PubMed
  • Cytokine, chemokine, and co-stimulatory fusion proteins for the immunotherapy of solid tumors Handb Exp Pharmacol. 2008; (181):291-328. . View in PubMed
  • RA8, a human anti-CD25 antibody against human Treg cells Hybridoma (Larchmt). 2007 Jun; 26(3):119-30. . View in PubMed
  • Lym-1-induced apoptosis of non-Hodgkin’s lymphomas produces regression of transplanted tumors Cancer Biother Radiopharm. 2007 Jun; 22(3):342-56. . View in PubMed
  • Targeted and untargeted CD137L fusion proteins for the immunotherapy of experimental solid tumors Clin Cancer Res. 2007 May 01; 13(9):2758-67. . View in PubMed
  • Soluble Fc fusion proteins for biomedical research Methods Mol Biol. 2007; 378:33-52. . View in PubMed
  • B71/NHS76: a new costimulator fusion protein for the immunotherapy of solid tumors. J Immunother. 2006 Jul-Aug; 29(4):425-35. . View in PubMed
  • H60/TNT-3 fusion protein activates NK cells in vitro and improves immunotherapeutic outcome in murine syngeneic tumor models J Immunother. 2006 May-Jun; 29(3):274-83. . View in PubMed
  • 131I-chTNT radioimmunotherapy of 43 patients with advanced lung cancer Cancer Biother Radiopharm. 2006 Feb; 21(1):5-14. . View in PubMed
  • Combination B7-Fc fusion protein treatment and Treg cell depletion therapy Clin Cancer Res. 2005 Dec 01; 11(23):8492-502. . View in PubMed
  • Generation of rituximab polymer may cause hyper-cross-linking-induced apoptosis in non-Hodgkin’s lymphomas Clin Cancer Res. 2005 Aug 15; 11(16):5971-80. . View in PubMed
  • NHS76/PEP2, a fully human vasopermeability-enhancing agent to increase the uptake and efficacy of cancer chemotherapy Clin Cancer Res. 2005 Apr 15; 11(8):3084-93. . View in PubMed
  • Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer J Clin Oncol. 2005 Mar 01; 23(7):1538-47. . View in PubMed
  • chTNT-3/hu IL-12 fusion protein for the immunotherapy of experimental solid tumors Hybrid Hybridomics. 2004 Feb; 23(1):1-10. . View in PubMed
  • Tumor targeting properties of indium-111 labeled genetically engineered Fab’ and F(ab’)2 constructs of chimeric tumor necrosis treatment (chTNT)-3 antibody Cancer Biother Radiopharm. 2003 Dec; 18(6):931-40. . View in PubMed
  • Complete regression of experimental solid tumors by combination LEC/chTNT-3 immunotherapy and CD25(+) T-cell depletion Cancer Res. 2003 Dec 01; 63(23):8384-92. . View in PubMed
  • Comparison of three different targeted tissue factor fusion proteins for inducing tumor vessel thrombosis Cancer Res. 2003 Aug 15; 63(16):5046-53. . View in PubMed
  • Chimeric TNT-3 antibody/murine interferon-gamma fusion protein for the immunotherapy of solid malignancies Hybrid Hybridomics. 2003 Aug; 22(4):197-207. . View in PubMed
  • LEC/chTNT-3 fusion protein for the immunotherapy of experimental solid tumors J Immunother. 2003 Jul-Aug; 26(4):320-31. . View in PubMed
  • Generation of low-toxicity interleukin-2 fusion proteins devoid of vasopermeability activity Blood. 2003 Jun 15; 101(12):4853-61. . View in PubMed
  • Chimeric TNT-3/human beta-glucuronidase fusion proteins for antibody-directed enzyme prodrug therapy (ADEPT) Cancer Biother Radiopharm. 2003 Jun; 18(3):339-53. . View in PubMed
  • Identification of a protein fragment of interleukin 2 responsible for vasopermeability J Natl Cancer Inst. 2003 May 21; 95(10):741-9. . View in PubMed
  • Neotrofin increases heme oxygenase-1 selectively in neurons Brain Res. 2003 Feb 07; 962(1-2):1-14. . View in PubMed
  • Comparison of recombinant derivatives of chimeric TNT-3 antibody for the radioimaging of solid tumors Hybrid Hybridomics. 2003 Feb; 22(1):1-9. . View in PubMed
  • Generation of human interferon gamma and tumor Necrosis factor alpha chimeric TNT-3 fusion proteins Hybrid Hybridomics. 2002 Dec; 21(6):421-32. . View in PubMed
  • Stable, genetically engineered F(ab’)(2) fragments of chimeric TNT-3 expressed in mammalian cells Hybrid Hybridomics. 2002 Feb; 21(1):11-8. . View in PubMed
  • Single amino acid substitution in the Fc region of chimeric TNT-3 antibody accelerates clearance and improves immunoscintigraphy of solid tumors J Nucl Med. 2000 Feb; 41(2):355-62. . View in PubMed
  • Pretreatment with a monoclonal antibody/interleukin-2 fusion protein directed against DNA enhances the delivery of therapeutic molecules to solid tumors Clin Cancer Res. 1999 Jan; 5(1):51-60. . View in PubMed
  • Improving monoclonal antibody pharmacokinetics via chemical modification Q J Nucl Med. 1998 Dec; 42(4):242-9. . View in PubMed
  • A new chemically modified chimeric TNT-3 monoclonal antibody directed against DNA for the radioimmunotherapy of solid tumors Cancer Biother Radiopharm. 1998 Aug; 13(4):255-68. . View in PubMed
  • Antitumor effects of nonconjugated murine Lym-2 and human-mouse chimeric CLL-1 monoclonal antibodies against various human lymphoma cell lines in vitro and in vivo Blood. 1997 Oct 15; 90(8):3160-6. . View in PubMed
  • Chimeric CLL-1 antibody fusion proteins containing granulocyte-macrophage colony-stimulating factor or interleukin-2 with specificity for B-cell malignancies exhibit enhanced effector functions while retaining tumor targeting properties Blood. 1997 Jun 15; 89(12):4437-47. . View in PubMed
  • Exploration of novel strategies to enhance monoclonal antibodies targeting Q J Nucl Med. 1997 Mar; 41(1):25-35. . View in PubMed
  • A chimeric Lym-1/interleukin 2 fusion protein for increasing tumor vascular permeability and enhancing antibody uptake Cancer Res. 1996 Nov 01; 56(21):4998-5004. . View in PubMed
  • Improved tumor localization and radioimaging with chemically modified monoclonal antibodies Cancer Biother Radiopharm. 1996 Jun; 11(3):203-15. . View in PubMed
  • Identification of a monoclonal antibody, TV-1, directed against the basement membrane of tumor vessels, and its use to enhance the delivery of macromolecules to tumors after conjugation with interleukin 2 Cancer Res. 1995 Jun 15; 55(12):2673-80. . View in PubMed
  • A human-mouse chimeric Lym-1 monoclonal antibody with specificity for human lymphomas expressed in a baculovirus system Hum Antibodies Hybridomas. 1995; 6(2):57-67. . View in PubMed
  • Effect of seven new vasoactive immunoconjugates on the enhancement of monoclonal antibody uptake in tumors Cancer. 1994 Feb 01; 73(3 Suppl):824-31. . View in PubMed
  • An improved method of direct labeling monoclonal antibodies with 99mTc Int J Rad Appl Instrum B. 1992 May; 19(4):445-54. . View in PubMed
  • m-[125I]iodoaniline: a useful reagent for radiolabeling biotin Int J Rad Appl Instrum B. 1992 Apr; 19(3):297-301. . View in PubMed
  • N-(m-[125I]iodophenyl)maleimide: an agent for high yield radiolabeling of antibodies Int J Rad Appl Instrum B. 1992 Apr; 19(3):289-95. . View in PubMed
  • Enhanced tumor uptake of macromolecules induced by a novel vasoactive interleukin 2 immunoconjugate Cancer Res. 1991 May 15; 51(10):2694-8. . View in PubMed
  • Synthesis of 125I labeled N-succinimidyl p-iodobenzoate for use in radiolabeling antibodies Int J Rad Appl Instrum B. 1989; 16(7):727-33. . View in PubMed
  • Inhibition of herpesvirus and human DNA polymerases by alpha-halogenated phosphonoacetates Biochem Pharmacol. 1987 Oct 01; 36(19):3103-6. . View in PubMed