Kenneth G. Lucas, M.D.

Kenneth G. Lucas, M.D.

Research Biography

Kenneth G. Lucas, M.D.
Professor of Medicine
Chief, Division of Hematology/Oncology and Stem Cell Transplantation
Department of Medicine


 

Clinical Expertise

Immunology, Stem Cell transplantation, Immunotherapy, Pediatric Cancer and Post-Transplant Infection

Board Certifications

  • American Board of Pediatrics and American Board of Pediatric Hematology/Oncology

    Education and Training

      • Medical School: State University of New York Health Science Center in Syracuse - 1989
      • Residency: Pediatrics – Children’s Hospital of Pittsburgh - 1992
      • Fellowship: Pediatric Hematology/Oncology – Memorial Sloan-Kettering Cancer Center in New York – 1995

        Publications

            1. Lucas K, Gula MJ, Blatt J.  Relapse in acute lymphoblastic leukemia as a function of white blood cell and absolute neutrophil counts during maintenance chemotherapy.  Pediatric Hematology and Oncology 9:91-7, 1992.
            2. Lucas KG, Urbach AH.  An unusual case of relapsing myositis in a 12-year-old child.  Clinical Pediatrics 32(7):438-442, 1993.
            3. Lucas K, Gula MJ, Knisely AS, Virgi MA, Wollman M, Blatt J.  Catecholamine metabolites in ganglioneuroma.  Medical and Pediatric Oncology 22: 240-243, 1994.
            4. Lucas KG, Kiehn TE, Sobeck KA, Armstrong D, Brown A. Sepsis caused by Flavimonas orzihabitansMedicine 73:209-14, 1994.
            5. Lucas KG, Brown AE.  Strongyloidiasis in the patient with cancer.  Infections in Medicine 12:181-186, 1995.
            6. Lucas KG, Howrie DL, Phebus CK.  Cardiorespiratory decompensation following methylprednisolone administration.  Pediatric Hematology and Oncology 10:249-255, 1993.
            7. Lucas K, Small TN, Dupont B, O’Reilly RJ.  The development of EBV-specific cellular immunity following allogeneic bone marrow transplantation.  Blood 87:2594-2603, 1996.
            8. Lucas KG, Brown AE, Armstrong D, Chapman D, Heller G.  The identification of febrile, neutropenic children with neoplastic disease at high risk for having positive blood cultures.  Cancer 77:791-798, 1996.
            9. Lucas KG.  Another look at granulocyte transfusions in neutropenic patients with cancer.  Infections in Medicine, 2:79, 1996.
            10. Dagher R, Lucas KG.  Toxoplasmosis in the immunocompromised patient.  Infections in Medicine 13:998, 1996.
            11. Lucas KG, Pollok KE, Emanuel DJ.  Post-transplant EBV induced lymphoproliferative disorders.  Leukemia and Lymphoma 25:1-8, 1997.
            12. Emanuel DJ, Lucas KG, Mallory GB, Edwards-Brown MK, Pollok KE, Conrad PD, Robertson KA, Stevens JC, Neiman RS, Givan D, Sahota AS, Smith FO.  Treatment of Epstein-Barr virus associated lymphoma in the central nervous system of a lung transplant recipient using HLA-matched allogeneic peripheral blood mononuclear cells.  Transplantation 63:1691-1694, 1997.
            13. Dagher R, Robertson KA, Lucas KG, Emanuel D, Smith FO.  Outpatient total body irradiation for pediatric patients undergoing stem cell transplantation.  Bone Marrow Transplantation, 19:1065-1067, 1997.
            14. Lucas KG, Burton RL, Pollok K, Emanuel DE.  Cord Blood Mononuclear Cell transformation assay for screening for the presence of Epstein - Barr virus.  J. Hematotherapy, 6:587-590, 1997.
            15. O’Reilly RJ, Small TN, Papadopoulos E, Lucas K, Lacerda J, Koulova L.  Biology and Adoptive Cell Therapy of Epstein-Barr Virus-Associated Lymphoproliferative Disorders in Recipients of marrow Allografts.  Immunological Reviews 157:195-216, 1997.
            16. Lucas KG, Emanuel DJ, Cornetta K, Zimmerman S, Lee CH.  Semi-quantitative EBV PCR for the Determination of Patients at Risk for EBV Induced Lymphoproliferative Disease following Stem Cell Transplantation.  Blood, 91:3654-3661, 1998.
            17. Lucas KG, Burton RL, Pollok KE, Emanuel DJ.  CD4+, Epstein Barr Virus Specific Cytotoxic T lymphocytes from Human Umbilical Cord Blood.  Cellular Immunology 195, 81-88, 1999.
            18. Sun Q, Pollok KE, Burton RL, Dai LJ, Britt W, Emanuel DJ, Lucas KG.  Simultaneous ex vivo expansion of cytomegalovirus and Epstein-Barr virus specific cytotoxic T-lymphocytes using B lymphoblastoid cell lines expressing CMV pp65.  Blood, 94:3242-3250, 1999.
            19. Barrett JC, Lucas KG.  Post-transplant lymphoproliferative disease. Herpes 7:1, 2000.
            20. Sun Q, Burton RL, Dai LJ, Britt W, Lucas KG.  B lymphoblastoid cells as efficient antigen-presenting cells to elicit CD8+ T cell responses against a cytomegalovirus antigen.  Journal of Immunology 165:4105-4111, 2000.
            21. Sun Q, Burton RL, Lucas KG.  Cytokine Production and Cytolytic Mechanism of CD4+ Cytotoxic T Lymphocytes in ex vivo Expanded Therapeutic EBV-specific T cell Cultures. Blood, 99:3302-9, 2002.
            22. Sun Q, Burton RL, Reddy V, Lucas KG.  Safety of Allogeneic Epstein-Barr Virus (EBV) Specific Cytotoxic T Lymphocytes for Patients with Refractory EBV-related Lymphoma. BritishJournal of Hematology, 118:799-808, 2002.
            23. Lucas KG, Salzman DE, Garcia A, Sun Q.  Adoptive Immunotherapy with Allogeneic Epstein Barr Virus Specific Cytotoxic T Lymphocytes for Relapsed, EBV Positive Hodgkin’s disease. Cancer 100: 1892-1901, 2004
            24. Comito MA, Sun Q, Lucas KG.  Immunotherapy for Epstein Barr Virus – Associated Tumors.  Leukemia and Lymphoma. 45:1981-1987, 2004.
            25. Lucas KG, Nelson JL, Erickson TD, Sun Q.  Microchimerism detection by human leucocyte antigen-specific quantitative-polymerase chain reaction analysis in recipients of allogeneic Epstein-Barr virus-specific cytotoxic T lymphocytes.  Br J Haematol. 129(3):443-4; 2005
            26. Lucas KF, Sun Q. Immunotherapy with virus-specific cytotoxic T lymphocytes after organ transplantation. Pediatr Transplantation. 10: 1-3; 2006.
            27. Lucas KG, Ungar D, Comito M, Bayerl M, Groh B.  Submyeloablative cord blood transplantation corrects clinical defects seen in IPEX syndrome.  Bone Marrow Transplant, 39(1):55-6, 2007.
            28. Bao L, Sun Q, Lucas KG.  Rapid Generation of CMV pp65 Specific T cells for Immunotherapy. Journal of Immunotherapy. 30: 557-561; 2007.
            29. Sun Q, Brewer N, Dunham K, Chen L, Bao L, Burton R, Lucas KG.  Interferon-gamma expressing EBV LMP2A-specific T cells for cellular immunotherapy.  Cellular Immunology, 246(2): 81-89, April 2007.
            30. Lucas KG, Ungar D, Comito M, Groh B.  Epstein Barr Virus Induced Lymphoma in a Child with IPEX Syndrome.  Pediatric Blood & Cancer, 9999, Sept 2007.
            31. Lucas KG, Schwartz C, Kaplan J. Allogeneic Stem Cell Transplantation in a Patient with Relapsed Ewing’s Sarcoma. Pediatric Blood & Cancer 2008; 51(1):142-4.
            32. Bao L, Dunham K, Stamer M, Mulieri K, Lucas K.  Expansion of CMV pp65 and IE-1 Specific Cytotoxic T Lymphocytes for CMV Specific Immunotherapy Following Allogeneic Stem Cell Transplant. Biology of Blood and Marrow Transplantation. 14, 10, 1156-62, Oct 2008.
            33. Bao L, Lucas K. Fusion of B Lymphoblastoid and Tumor Cells Expressing Different Antibiotic Resistance Genes Facilitates Selection of Stable Hybridomas. Hybridoma.27, 5, 401-405. 2008.
            34. Horn B, Bao L, Dunham K, Stamer M, Adler S, Cowan M, Lucas KG. Infusion of pp65 CTL from a seronegative donor can facilitate resolution of CMV infection and immune reconstitution. Ped Inf Disease Journal. 2009; 28:65-67.
            35. Lucas KG. Shapiro T. Freiberg A. Frauenhoffer E. Matched unrelated umbilical cord blood transplantation for a patient with chemotherapy resistant Wilms tumor. Pediatric Blood & Cancer. 55(4):763-5, 2010.
            36. Lucas KG, Bao L, Bruggeman R, Dunham K, Specht C. The detection of CMV pp65 and IE1 in glioblastoma multiforme. J Neuro-Oncology, published on-line Sept 7, 2010.
            37. Huang, M, Bayerl, M, Lucas, K. An instructive case of hypercalcemia preceding relapse of AML following allogeneic BMT. Bone Marrow Transplantation, Jul;46(7):1028-9 2011
            38. Huang M, Lucas KG. Current Therapeutic Approaches in Metastatic and Recurrent Ewing’s Sarcoma. Sarcoma, 2011:863210  PMCID: PMC2995926
            39. Bao L, Dunham, K, Lucas KG. Upregulation of MAGE-A1, MAGE-A3, NY-ESO-1 and MHC Molecules on Neuroblastoma Cells Following Exposure to Decitabine and Interferon-γ. Cancer Immunol and Immunotherapy, 2011 Sep;60(9):1299-307.
            40. Kolaseri Krishnadas D, Stamer, MS, Bao, L, Lucas KG. Polyclonal, Wilms’ tumor 1-specific cytotoxic T lymphocytes that kill leukemia cells can be expanded from adult donors and cord blood. Leukemia Research, 2011 Nov;35(11):1520-6.
            41. Bao L, Horn B, Cowan M, McGuirk, J, Gilman A, Lucas KG. Adoptive Immunotherapy with CMV pp65 Specific Cytotoxic T Lymphocytes for Stem Cell Transplant Patients with Refractory CMV Infections. J Immunother. 2012 Apr;35(3):293-8. PMID: 22421947 [PubMed - in process]
            42. Abbi KK, Zhu J, Ehmann WC, Epner E, Carraher M, Mierski J, Talamo G, Lucas K, Rybka W, Claxton D. G-CSF mobilized vs conventional donor lymphocytes for therapy of relapse or incomplete engraftment after allogeneic hematopoietic transplantation. Bone Marrow Transplant. 2012 Aug 6. doi: 10.1038/bmt.2012.144.
            43. Krishnadas DK, Shapiro T, Lucas K. Complete remission following decitabine/dendritic cell vaccine for relapsed neuroblastoma.Pediatrics. 2013 Jan;131(1):e336-41.
            44. Krishnadas DK, Bai F and Lucas K. Cancer testis antigen and immunotherapy. ImmunoTargets and Therapy. 2013. 2013(2):11-19

             

            Grants, Contracts, and Other Funding

            1.    Completed
            a.    “The Use of Antigen Presenting Cell-tumor Cell Hybridomas to Stimulate ex vivo Expansion of Tumor Specific CTL”
            Four Diamonds Fund Research Program
            Principal Investigator
            1/1/2004 – 12/31/2004
            $37,500

            b.    “Adoptive Immunotherapy for EBV Positive Hodgkin’s Disease”
            NIH /  NCI (R-21 CA91537-01A1)  
            Principal Investigator        
            25% effort    
            9/1/2001 - 8/31/2005  
            $700,000

            c.    “Reduced Intensity Conditioning Hematopoietic Cell Transplant”
            Pediatric Bone Marrow Transplant Consortium
            Principal Investigator         
            No % effort
            12/15/2003 - 2/2007
            $ 5,000    


            d.    “Cytokine Gene Polymorphisms in Pediatric Patients w/ GVHD”
            Fujisawa
            Principal Investigator         
            No % effort
            12/15/2003 - 12/30/2005
            $2,500

            e.    “SCID Model for T Cell Therapy Against Epstein-Barr Virus Related Lymphoma”
            Children’s Miracle Network Research Funds
            Co – Investigator (PI: Qi Sun)    
            No % effort
            7/1/2005 – 6/30/2006
            $60,000

            f.    “The Development of Tumor-B Lymphoblastoid Cell Hybridomas for Vaccination into High Risk Neuroblastoma and Ewing Sarcoma Patients”
            Children’s Miracle Network Research Funds
            Principal Investigator        
            50% effort
            7/1/2006 – 6/30/2007
            $60,000

            g.    “Tumor Cell Hybridoma Vaccine for Recurrent Neuroblastoma and Ewing’s Sarcoma”
            Alex’s Lemonade Stand
            Principal Investigator
            5% Effort
            11/1/2006 – 10/31/2007
            $100,000

            h.    “Adoptive Cellular Immunotherapy for EBV and CMV Disease
            Tobacco Settlement Fund MD Research Facilitation Award”
            Principal Investigator             
            25% Effort
            12/26/2006 – 12/31/2007
            $63,216

            i.    “Virus Specific CTL Following T Cell Depleted SCT”
            National Institutes of Health (R01 CA 106319)
            Principal Investigator        
            20% effort
            2/1/2005 - 12/31/2011
            $1,000,000
            j.     “A Phase I Trial Combining Decitabine and Vaccine Therapy for Patients with Neuroblastoma”
            Hyundai Hope of Wheels
            Principal Investigator
            10% effort
            09/01/2011 - 12/1/2012
            $100,000

            k.    “Decitabine and CT Antigen Vaccine for Patients with Relapsed Neuroblastoma”
            Solving Kids Cancer
            Principal Investigator
            10% effort
            07/15/2011 - 06/30/2013
            $207,000

            l.    “Virus and Leukemia Specific Cytotoxic T Lymphocytes Expanded Simultaneously
            for Post-Transplant Immunotherapy”Children’s Miracle Network CMN 132699
            Principal Investigator
            5% effort
            07/01/2011 - 6/30/2012
            $20,000

            Active

            Pending

            NIH (PI: Lucas, K)                             11/01/2013 - 10/31/2017
            $ 2,078,894
            “Decitabine with Vaccine Therapy for Relapsed Glioblastoma”

            In this study we will use a novel chemo-immunotherapy approach in patients with relapsed glioblastoma multiforme (GBM). The demethylating agent decitabine (DAC) will be administered to upregulate the expression of MAGE-A1, MAGE-A3, and NY-ESO-1 on tumor cells, prior to the administration of an autologous dendritic cell (DC)/CT antigen vaccine. We hypothesize that > 30% of subjects will have progression free survival at six months post-relapse, and that > 50% of subjects will have either new onset or two-fold increases in CT antigen specific immune responses post-vaccination. We will study the potential role of blocking regulatory T cells (Treg) in promoting immune responses to CT antigens in these patients, and conduct studies to understand the mechanisms whereby DAC promotes GBM tumor cell killing.

             

            Current Clinical Trial Activities

            Institutional studies

            The Use of Umbilical Cord Blood as a Source of Hematopoietic Stem Cells (PI)
            Pharmacologic Upregulation of Cancer Testis Antigens Followed by Vaccine Therapy for Patients with Relapsed Acute Myelogenous Leukemia Following Allogeneic Stem Cell Transplantation (PI)
            Multi-center studies:  
            A Phase I Trial Combining Decitabine and Vaccine Therapy for Patients with Neuroblastoma (PI)
            Defibrotide for Patients with Hepatic Veno-occlusive Disease (VOD): A Treatment IND Study (Institutional PI, industry sponsored through Gentium)

            A Multi-Center, Randomized, Double Blind, Phase III Trial Evaluating Corticosteroids with Mycophenolate Mofetil vs. Corticosteroids with Placebo as Initial Systemic Treatment of Acute GVHD (A BMT Clinical Trials Network study; institutional PI)

            A Phase I Trial to Examine the Safety, Clinical, Immunologic and Virologic Effects
            of CMV pp65/IE-1 Specific Cytotoxic T Lymphocytes for Recipients of Allogeneic Stem Cell Transplants with Persistent or Therapy Refractory Infections (PI)-  recently completed

            Completed Research Support

            RO1 CA 106319                 Lucas, K                        02/01/2005-12/31/2011
            “Virus Specific CTL Following T Cell Depleted SCT”
            The clinical, immunologic, and virologic effects of prophylactic CMB/EBV specific CTL is compared in recipients of allogeneic, TCD SCT with a control group of TCD SCT patients randomized to not receive CTL.  CD4 & CD8 antigen specific immune reconstitution (CTL precursor frequencies) and CMV and EBV DNA levels (by real time PCR) will be compared in these groups at intervals post-transplant. We will determine which CMVpp65 epitopes are immunodominant in stem cell donors.  Dominant epitopes of the CTL donors will be compared with those found in CTL recipients post-infusion, to determine whether immunodominant epitopes recognized by the donor are retained in the recipient and if not which epitopes are most relevant post-transplant. These studies will determine the impact on viral reactivation and immune reconstitution of prophylactic antigen-specific CTL and will serve as a groundwork for extending this system of antigen presentation and T cell expansion to other pathogens as well as tumor antigens in the future.
            Role: PI

            Children’s Miracle Network             Lucas, K                            07/01/2011-6/30/2012
            “Virus and Leukemia Specific Cytotoxic T Lymphocytes Expanded Simultaneously for Post-Transplant Immunotherapy”
            The clinical, immunologic, and virologic effects of prophylactic CMB/EBV specific CTL is compared in recipients of allogeneic, TCD SCT with a control group of TCD SCT patients randomized to not receive CTL.  CD4 & CD8 antigen specific immune reconstitution (CTL precursor frequencies) and CMV and EBV DNA levels (by real time PCR) will be compared in these groups at intervals post-transplant. We will determine which CMVpp65 epitopes are immunodominant in stem cell donors.  Dominant epitopes of the CTL donors will be compared with those found in CTL recipients post-infusion, to determine whether immunodominant epitopes recognized by the donor are retained in the recipient and if not which epitopes are most relevant post-transplant. These studies will determine the impact on viral reactivation and immune reconstitution of prophylactic antigen-specific CTL and will serve as a groundwork for extending this system of antigen presentation and T cell expansion to other pathogens as well as tumor antigens in the future.
            Role: PI

            Hyundai Hope on Wheels                 Lucas, K                             09/01/2011-12/1/2012
            “A Phase 1 Trial Combining Decitabine and Vaccine Therapy for Patients with Neuroblastoma”
            Patient specimens are analyzed post vaccine to determine whether there has been an immune response to the vaccine.  Experiments are also performed to determine how best to grow MAGE-A1, MAGE-A3,and NY-ESO-1 antigen specific T cells from these patients.  In addition, it will be determined whether interferon-     (IFN-     ) or CD137 (an activation marker) based selection is superior for isolation of these CTL using the CliniMACS system from Miltenyi Biotech.  
            Role:

            Ongoing Research Support

            Solving Kids Cancer            Lucas, K.                        07/15/2011–6/30/2013
            “Decitabine and CT Antigen Vaccine for Patients with Relapsed Neuroblastoma”
            The purpose of this study is to characterize clinical and immunologic responses following a regimen of DAC and a dendritic cell- MAGE-A1, MAGE-A3, and NY-ESO-1 vaccine in patients with relapsed neuroblastoma.
            Role: PI

            Pending Research Support

            Lucas, K                        10/01/2012-09/30/2017

            “Phase 1 Trial Combining Decitabine and Vaccine Therapy for Patients with Neuroblastoma”
            Cellular immune responses to developed vaccine will be analyzed.  Relapsed osteogenic sarcoma, rhabdomyosarcoma, synovial sarcoma, and Ewing’s sarcoma have been recently added to the tumors we are studying.  Other objectives include a determination of whether previously characterized MAGE-A1, MAGE-A3, and NY-ESO-1 epitopes are recognized by patients who have received this vaccine, and a determination of the methods of tumor cell killing from CTL derived from patient specimens.
            Role: PI

            Invited Lectures/Presentations

            09/25/1998    “Post-transplant lymphoproliferative disease”
            American Society for Microbiology Annual Meeting (Interscience Conference)

            10/08/1999    “CMV and EBV Specific Cytotoxic T Lymphocytes for Immunotherapy
            Following T cell Depleted Stem Cell Transplants”
            National Marrow Donor Program Annual Meeting        

            05/2000    Hematology-Oncology Grand Rounds, Memorial Sloan Kettering Cancer Center
            “Adoptive Immunotherapy for EBV and CMV Disease using Genetically Modified Antigen Presenting Cells”

            11/25/2003    “Pediatric Stem Cell Transplantation”
            Pediatric Grand Rounds
            Penn State Children’s Hospital, Hershey, PA

            03/30/2004    “Pediatric Stem Cell Transplant”
            Geisinger Medical Center, Danville, PA     

            01/15/2004    “Adoptive Immunotherapy for EBV related Malignancies” Hematology-Oncology Grand Rounds, Penn State Hershey Medical Center.

            05/19/2004    “Pediatric Stem Cell Transplantation”
            Pediatric Grand Rounds
            Wilkes-Barre Hospital, Wilkes Barre, PA

            02/02/2005    “Pediatric Stem Cell Transplant Update”
            Reading Area CME Lecture
            Reading Hospital, Reading, PA

            2/11/2005      “Immunotherapy for EBV Positive Hodgkin’s Disease”
            Presentation at the American Society for Blood and Marrow Transplantation Annual Meeting

            02/25/2005    “Targeting EBV-Related Hodgkin’s Lymphoma”
            Regional Cancer Center Consortium for the Biological Therapy of Cancer

            04/06/2005    “Pediatric Stem Cell Transplant”
            Grand Rounds
            York Hospital, York, PA

            04/19/2005    “Immunotherapy for EBV+ Hodgkin’s Disease”
            Interdisciplinary Presentation – Penn State Hershey Cancer Institute

            12/02/2005    “Immune Deficiency Disorders”
            Pediatric Grand Rounds, Reading Hospital, Reading, PA

            05/04/2006    “Inherited Immunodeficiency Syndromes”
            Pediatric Grand Rounds, York Hospital, York, PA

            08/2006    “Cellular Immunotherapy for Prophylaxis of CMV Infections”
            Winship Cancer Institute, Emory University, Hematology/Oncology Research Conference (Atlanta, Georgia)

            10/16/2007    “Adoptive Immunotherapy for Stem Cell Transplant Patients with  
            Persistent/ Therapy Refractory Cytomegalovirus Infections”, Pediatric Blood and Marrow Transplant Consortium Annual Meeting

            10/21/2008     “An Overview of Pediatric Stem Cell Transplant: Current Indications and New Areas of Investigation” Pediatric Grand Rounds, Geisinger Medical Center, Danville, PA

            2/17/2009     “Current Indications and Trends and Pediatric Stem Cell Transplantation”
            Pinnacle Health Pediatric Grand Rounds, Harrisburg, PA

            05/2009    “Pediatric Stem Cell Transplant Update”
            Grand Rounds, Penn State Hershey Children’s Hospital

            6/2009       ”An Overview of Current Trends in Immunotherapy and Transplant Research, an Interdisciplinary Conference for Pediatric Oncology and Stem Cell Transplant Providers (Hershey Lodge, Hershey PA)

            8/2009        “Pediatric Stem Cell Transplant Update”
            Pediatric Grand Rounds, York PA

            11/3/2010    “Pediatric Stem Cell Transplant: Current Indications and New Trends”
            Pediatric Grand Rounds, York, PA

            11/5/2010    ‘Current Concepts and Challenges in Adoptive Immunotherapy”
            Pediatric Grand Rounds, Children’s Hospital of Michigan

            Manuscript Submitted

            1.    Krishnadas DK, Bai F and Lucas K. Cancer Testis Antigen and Immunotherapy. ImmunoTargets and Therapy