Rimas Orentas, PhD

Rimas Orentas, PhD

Children's Title: Principal Investigator, Ben Towne Center for Childhood Cancer Research

Research Center: Ben Towne Center for Childhood Cancer Research

"My passion is to understand how the immune system can be brought to bear on childhood cancer. Using the advanced tools that genomics provides, and the ability to engineer T cells with gene vectors, our lab works to unravel the defense mechanisms that tumors employ to avoid detection and elimination, and to engineer T cells to recognize and destroy malignant cells, with a special emphasis on solid tumors like rhabdomyosarcoma, osteosarcoma and neuroblastoma."

  • I graduated with a bachelor's degree in Microbiology from the University of Maryland, College Park, and a doctorate of philosophy from The Johns Hopkins University School of Medicine, Department of Pharmacology and Molecular Sciences. After a post-doctoral fellowship and research associate position at the Johns Hopkins Oncology Center, I was appointed to the faculty of the Medical College of Wisconsin. There I rose to the rank of Associate Professor with a primary appointment in Pediatrics, Section of Hematology-Oncology, with additional appointments in the Department of Microbiology and Molecular Genetics and the Department of Medicine. I then worked at Lentigen Corp., focusing on lentiviral gene vector development for the transduction of human T cells and hematopoietic stem cells. This was followed by an appointment as a staff scientist and then associate scientist in the Pediatric Oncology Branch of the National Cancer Institute's Center for Cancer Research at the National Institutes of Health (NIH). I then returned to Lentigen Technology, Inc., a Miltenyi Biotec Company where I served as scientific director, establishing a basic science and clinical therapeutics program. Currently I am a principal investigator at the Ben Towne Center for Cancer Research and also serve as the director for scientific integration at CureWorks, part of the Immunology Integration Hub of the Seattle Children's Research Institute.

  • Other Publications

    • Zhu F, Shah N, Xu H, Schneider D, Orentas R, Dropulic B, Hari P, Keever-Taylor CA
      Closed-system manufacturing of CD19 and dual-targeted CD20/19 chimeric antigen receptor T cells using the CliniMACS Prodigy device at an academic medical center.
      29287970 Cytotherapy, 2018 March : 20(3)394-406
    • Moore T, Wagner CR, Scurti GM, Hutchens KA, Godellas C, Clark AL, Kolawole EM, Hellman LM, Singh NK, Huyke FA, Wang SY, Calabrese KM, Embree HD, Orentas R, Shirai K, Dellacecca E, Garrett-Mayer E, Li M, Eby JM, Stiff PJ, Evavold BD, Baker BM, Le Poole IC, Dropulic B, Clark JI, Nishimura MI
      Clinical and immunologic evaluation of three metastatic melanoma patients treated with autologous melanoma-reactive TCR-transduced T cells.
      29052782 Cancer immunology, immunotherapy : CII, 2018 Feb. : 67(2)311-325 PMCID:PMC5935006
    • Fry TJ, Shah NN, Orentas RJ, Stetler-Stevenson M, Yuan CM, Ramakrishna S, Wolters P, Martin S, Delbrook C, Yates B, Shalabi H, Fountaine TJ, Shern JF, Majzner RG, Stroncek DF, Sabatino M, Feng Y, Dimitrov DS, Zhang L, Nguyen S, Qin H, Dropulic B, Lee DW, Mackall CL
      CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy.
      29155426 Nature medicine, 2018 Jan. : 24(1)20-28 PMCID:PMC5774642
    • Walker AJ, Majzner RG, Zhang L, Wanhainen K, Long AH, Nguyen SM, Lopomo P, Vigny M, Fry TJ, Orentas RJ, Mackall CL
      Tumor Antigen and Receptor Densities Regulate Efficacy of a Chimeric Antigen Receptor Targeting Anaplastic Lymphoma Kinase.
      28676342 Molecular therapy : the journal of the American Society of Gene Therapy, 2017 Sept. 6 : 25(9)2189-2201 PMCID:PMC5589087
    • Orentas RJ, Sindiri S, Duris C, Wen X, He J, Wei JS, Jarzembowski J, Khan J
      Paired Expression Analysis of Tumor Cell Surface Antigens.
      28871274 Frontiers in oncology, 2017 : 7173 PMCID:PMC5566986
    • Schneider D, Xiong Y, Wu D, NÓ§lle V, Schmitz S, Haso W, Kaiser A, Dropulic B, Orentas RJ
      A tandem CD19/CD20 CAR lentiviral vector drives on-target and off-target antigen modulation in leukemia cell lines.
      28515942 Journal for immunotherapy of cancer, 2017 : 542 PMCID:PMC5433150
    • Long AH, Highfill SL, Cui Y, Smith JP, Walker AJ, Ramakrishna S, El-Etriby R, Galli S, Tsokos MG, Orentas RJ, Mackall CL
      Reduction of MDSCs with All-trans Retinoic Acid Improves CAR Therapy Efficacy for Sarcomas.
      27549124 Cancer immunology research, 2016 Oct. : 4(10)869-880 PMCID:PMC5050151
    • Qin H, Cho M, Haso W, Zhang L, Tasian SK, Oo HZ, Negri GL, Lin Y, Zou J, Mallon BS, Maude S, Teachey DT, Barrett DM, Orentas RJ, Daugaard M, Sorensen PH, Grupp SA, Fry TJ
      Eradication of B-ALL using chimeric antigen receptor-expressing T cells targeting the TSLPR oncoprotein.
      26041741 Blood, 2015 July 30 : 126(5)629-39 PMCID:PMC4520878
    • Long AH, Haso WM, Shern JF, Wanhainen KM, Murgai M, Ingaramo M, Smith JP, Walker AJ, Kohler ME, Venkateshwara VR, Kaplan RN, Patterson GH, Fry TJ, Orentas RJ, Mackall CL
      4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors.
      25939063 Nature medicine, 2015 June : 21(6)581-90 PMCID:PMC4458184
    • Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN, Steinberg SM, Stroncek D, Tschernia N, Yuan C, Zhang H, Zhang L, Rosenberg SA, Wayne AS, Mackall CL
      T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial.
      25319501 Lancet (London, England), 2015 Feb. 7 : 385(9967)517-528
    • Orentas RJ, Mackall CL
      Emerging Immunotherapies for Cancer and Their Potential for Application in Pediatric Oncology.
      26349422 Critical reviews in oncogenesis, 2015 : 20(3-4)315-27
    • Kroesen M, Nierkens S, Ansems M, Wassink M, Orentas RJ, Boon L, den Brok MH, Hoogerbrugge PM, Adema GJ
      A transplantable TH-MYCN transgenic tumor model in C57Bl/6 mice for preclinical immunological studies in neuroblastoma.
      24038106 International journal of cancer, 2014 March 15 : 134(6)1335-45
    • Orentas RJ, Nordlund J, He J, Sindiri S, Mackall C, Fry TJ, Khan J
      Bioinformatic description of immunotherapy targets for pediatric T-cell leukemia and the impact of normal gene sets used for comparison.
      24959420 Frontiers in oncology, 2014 : 4134 PMCID:PMC4050364
    • Zhang H, Maric I, DiPrima MJ, Khan J, Orentas RJ, Kaplan RN, Mackall CL
      Fibrocytes represent a novel MDSC subset circulating in patients with metastatic cancer.
      23757729 Blood, 2013 Aug. 15 : 122(7)1105-13 PMCID:PMC3744987
    • Long AH, Haso WM, Orentas RJ
      Lessons learned from a highly-active CD22-specific chimeric antigen receptor.
      23734316 Oncoimmunology, 2013 April 1 : 2(4)e23621 PMCID:PMC3654586
    • Orentas RJ
      Reading the tea leaves of tumor-mediated immunosuppression.
      23430024 Clinical cancer research : an official journal of the American Association for Cancer Research, 2013 March 1 : 19(5)955-7 PMCID:PMC3594479
    • Haso W, Lee DW, Shah NN, Stetler-Stevenson M, Yuan CM, Pastan IH, Dimitrov DS, Morgan RA, FitzGerald DJ, Barrett DM, Wayne AS, Mackall CL, Orentas RJ
      Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia.
      23243285 Blood, 2013 Feb. 14 : 121(7)1165-74 PMCID:PMC3575759
    • Stauffer JK, Orentas RJ, Lincoln E, Khan T, Salcedo R, Hixon JA, Back TC, Wei JS, Patidar R, Song Y, Hurd L, Tsokos M, Lai EW, Eisenhofer G, Weiss W, Khan J, Wigginton JM
      High-throughput molecular and histopathologic profiling of tumor tissue in a novel transplantable model of murine neuroblastoma: new tools for pediatric drug discovery.
      22571338 Cancer investigation, 2012 June : 30(5)343-63
    • Lee DW, Barrett DM, Mackall C, Orentas R, Grupp SA
      The future is now: chimeric antigen receptors as new targeted therapies for childhood cancer.
      22589486 Clinical cancer research : an official journal of the American Association for Cancer Research, 2012 May 15 : 18(10)2780-90 PMCID:PMC4119811
    • Orentas RJ, Yang JJ, Wen X, Wei JS, Mackall CL, Khan J
      Identification of cell surface proteins as potential immunotherapy targets in 12 pediatric cancers.
      23251904 Frontiers in oncology, 2012 : 2194 PMCID:PMC3523547
    • Orentas RJ, Lee DW, Mackall C
      Immunotherapy targets in pediatric cancer.
      22645714 Frontiers in oncology, 2012 : 23 PMCID:PMC3355840
    • Meadors JL, Cui Y, Chen QR, Song YK, Khan J, Merlino G, Tsokos M, Orentas RJ, Mackall CL
      Murine rhabdomyosarcoma is immunogenic and responsive to T-cell-based immunotherapy.
      21462302 Pediatric blood and cancer, 2011 Dec. 1 : 57(6)921-9
    • Zheng J, Orentas R, Yan X, Liu H
      Humoral immune response induced by an engineered cell-based neuroblastoma vaccine with or without CD25 blockade.
      21266542 Acta biochimica et biophysica Sinica, 2011 Feb. : 43(2)124-32
    • Kohler ME, Johnson BD, Palen K, Chen QR, Khan J, Orentas RJ
      Tumor antigen analysis in neuroblastoma by serological interrogation of bioinformatic data.
      20718755 Cancer science, 2010 Nov. : 101(11)2316-24 PMCID:PMC3103783
    • Norell H, Zhang Y, McCracken J, Martins da Palma T, Lesher A, Liu Y, Roszkowski JJ, Temple A, Callender GG, Clay T, Orentas R, Guevara-Patiño J, Nishimura MI
      CD34-based enrichment of genetically engineered human T cells for clinical use results in dramatically enhanced tumor targeting.
      20052466 Cancer immunology, immunotherapy : CII, 2010 June : 59(6)851-62 PMCID:PMC3736983
    • Kohler ME, Hallett WH, Chen QR, Khan J, Johnson BD, Orentas RJ
      Early expression of stem cell-associated genes within the CD8 compartment after treatment with a tumor vaccine.
      20692654 Cellular immunology, 2010 : 265(1)65-73 PMCID:PMC2935508
    • Zheng J, Jing W, Orentas RJ
      Discovery of YB-1 as a new immunological target in neuroblastoma by vaccination in the context of regulatory T cell blockade.
      20011972 Acta biochimica et biophysica Sinica, 2009 Dec. : 41(12)980-90
    • Yan X, Johnson BD, Orentas RJ
      Induction of a VLA-2 (CD49b)-expressing effector T cell population by a cell-based neuroblastoma vaccine expressing CD137L.
      18802064 Journal of immunology (Baltimore, Md. : 1950), 2008 Oct. 1 : 181(7)4621-31 PMCID:PMC2975591
    • Zhou Q, Yan X, Gershan J, Orentas RJ, Johnson BD
      Expression of macrophage migration inhibitory factor by neuroblastoma leads to the inhibition of antitumor T cell reactivity in vivo.
      18641325 Journal of immunology (Baltimore, Md. : 1950), 2008 Aug. 1 : 181(3)1877-86 PMCID:PMC3804024
    • Saad ER, Bresnahan BA, Cohen EP, Lu N, Orentas RJ, Vasudev B, Hariharan S
      Successful treatment of BK viremia using reduction in immunosuppression without antiviral therapy.
      18360267 Transplantation, 2008 March 27 : 85(6)850-4
    • Prosser SE, Orentas RJ, Jurgens L, Cohen EP, Hariharan S
      Recovery of BK virus large T-antigen-specific cellular immune response correlates with resolution of bk virus nephritis.
      18212622 Transplantation, 2008 Jan. 27 : 85(2)185-92
    • Zheng J, Kohler ME, Chen Q, Weber J, Khan J, Johnson BD, Orentas RJ
      Serum from mice immunized in the context of Treg inhibition identifies DEK as a neuroblastoma tumor antigen.
      17397536 BMC immunology, 2007 March 30 : 84 PMCID:PMC1852119
    • Jing W, Orentas RJ, Johnson BD
      Induction of immunity to neuroblastoma early after syngeneic hematopoietic stem cell transplantation using a novel mouse tumor vaccine.
      17317581 Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2007 March : 13(3)277-92 PMCID:PMC1852542
    • Johnson BD, Jing W, Orentas RJ
      CD25+ regulatory T cell inhibition enhances vaccine-induced immunity to neuroblastoma.
      17471167 Journal of immunotherapy (Hagerstown, Md. : 1997), 2007 Feb. : 30(2)203-14
    • Zhou Q, Johnson BD, Orentas RJ
      Cellular immune response to an engineered cell-based tumor vaccine at the vaccination site.
      17543914 Cellular immunology, 2007 Feb. : 245(2)91-102 PMCID:PMC1949498
    • Orentas RJ, Kohler ME, Johnson BD
      Suppression of anti-cancer immunity by regulatory T cells: back to the future.
      16376101 Seminars in cancer biology, 2006 April : 16(2)137-49
    • Yan X, Orentas RJ, Johnson BD
      Tumor-derived macrophage migration inhibitory factor (MIF) inhibits T lymphocyte activation.
      16522371 Cytokine, 2006 Feb. 21 : 33(4)188-98 PMCID:PMC2018658
    • Jurgens LA, Khanna R, Weber J, Orentas RJ
      Transduction of primary lymphocytes with Epstein-Barr virus (EBV) latent membrane protein-specific T-cell receptor induces lysis of virus-infected cells: A novel strategy for the treatment of Hodgkin's disease and nasopharyngeal carcinoma.
      16418800 Journal of clinical immunology, 2006 Jan. : 26(1)22-32 PMCID:PMC3056547
    • Hariharan S, Cohen EP, Vasudev B, Orentas R, Viscidi RP, Kakela J, DuChateau B
      BK virus-specific antibodies and BKV DNA in renal transplant recipients with BKV nephritis.
      16212632 American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2005 Nov. : 5(11)2719-24
    • Johnson BD, Gershan JA, Natalia N, Zujewski H, Weber JJ, Yan X, Orentas RJ
      Neuroblastoma cells transiently transfected to simultaneously express the co-stimulatory molecules CD54, CD80, CD86, and CD137L generate antitumor immunity in mice.
      16113601 Journal of immunotherapy (Hagerstown, Md. : 1997), 2005 Sept. : 28(5)449-60
    • Gershan JA, Johnson BD, Weber J, Schauer DW, Natalia N, Behnke S, Burns K, Maloney KW, Warwick AB, Orentas RJ
      Immediate transfection of patient-derived leukemia: a novel source for generating cell-based vaccines.
      15969754 Genetic vaccines and therapy, 2005 June 21 : 3(1)4 PMCID:PMC1182385
    • Yan X, Johnson BD, Orentas RJ
      Murine CD8 lymphocyte expansion in vitro by artificial antigen-presenting cells expressing CD137L (4-1BBL) is superior to CD28, and CD137L expressed on neuroblastoma expands CD8 tumour-reactive effector cells in vivo.
      15096190 Immunology, 2004 May : 112(1)105-16 PMCID:PMC1782467
    • Rosenblum MD, Olasz E, Woodliff JE, Johnson BD, Konkol MC, Gerber KA, Orentas RJ, Sandford G, Truitt RL
      CD200 is a novel p53-target gene involved in apoptosis-associated immune tolerance.
      14644999 Blood, 2004 April 1 : 103(7)2691-8
    • Orentas RJ, Schauer DW Jr, Ellis FW, Walczak J, Casper JT, Margolis DA
      Monitoring and modulation of Epstein-Barr virus loads in pediatric transplant patients.
      12890010 Pediatric transplantation, 2003 Aug. : 7(4)305-14
    • Johnson BD, Yan X, Schauer DW, Orentas RJ
      Dual expression of CD80 and CD86 produces a tumor vaccine superior to single expression of either molecule.
      12798304 Cellular immunology, 2003 March : 222(1)15-26
    • Bin Q, Johnson BD, Schauer DW, Casper JT, Orentas RJ
      Production of macrophage migration inhibitory factor by human and murine neuroblastoma.
      12218292 Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2002 May : 23(3)123-9