Scientific Program

Distinguished Lecturers

Professor Hideho Okada Kathleen M. Plant Distinguished Professor in Neurological Surgery, U.S.A.
EDUCATION/TRAINING
INSTITUTION AND LOCATION DEGREE Completion Date FIELD OF STUDY
Nagoya University School of Medicine-Japan MD 03/1991 Medicine
Nagoya University School of Medicine-Japan PhD 03/1996 Medicine
Handa Municipal Hospital-Japan Internship 03/1992  
Nagoya University Hospital, Dept. Neurosurgery Residency 03/1996 Neurosurgery

A. Personal Statement

As a physician–scientist, I have been dedicated to brain tumor immunology and development of effective immunotherapy for brain tumor patients for over 20 years. My team was one of very first to discover cytotoxic T lymphocyte (CTL) epitopes in glioma-associated and glioma-specific antigens (Section C-1 below). I also found critical roles for the integrin receptor very late activation antigen (VLA)-4 and the chemokine CXCL10 in facilitating entry of CTLs to the brain tumor site (C-2). I have translated these discoveries into a number of innovative immunotherapy clinical studies, such as one with chimeric antigen receptor (CAR)-transduced T-cells, in both adult and pediatric brain tumor patients (C-3). In addition to institutional and bi-institutional trials, our team’s discoveries have led to two currently active multicenter trials (NCT02078648 and NCT02960230), each involving 15 or more sites. Furthermore, I lead an international group of brain tumor immunotherapy experts to develop novel iRANO criteria (C-3). All of my preclinical inventions, such as CTL epitopes and CARs, have been proven to be reproducible by demonstrations of their robust biological activities in subsequent clinical trials. In addition to development of novel immunotherapy approaches, my team has also pioneered in discoveries of novel immunoregulatory mechanisms in gliomas, such as one mediated by myeloid-derived suppressor cells (MDSC) and mutations of the isocitrate dehydrogenase (IDH) enzymes IDH1 and IDH2 (C-4).
In terms of national and international recognition in the field, I am an elected member in the American Society for Clinical Investigation (2010-present), an honored society for physicians who promote laboratory science to the clinic. My recent national and international leadership roles include: Chair of the Immunotherapy Subgroup at the NCI-sponsored Adult Brain Tumor Consortium (2013-present); a Steering Committee member of the Cancer Immunology Working Group in the American Association for Cancer Research (AACR; 2013-2016); a co-chair for Education Day at 2015 the Society for Neuro-Oncology (SNO) annual meeting; an organizing committee member for the 2015 Annual Meeting of the AACR; and a committee member of Advances in Cancer Immunotherapy in Society for Immunotherapy of Cancer (2015-present). Most recently, I have been appointed to be the Chair of the AACR Special Conference “Immunobiology of Primary and Metastatic CNS Cancer: Multidisciplinary Science to Advance Cancer Immunotherapy” (February 15-18, 2018, San Diego, CA). I have designed this to be an unprecedented type of interdisciplinary conference, in which we will integrate advancements of basic brain immunology, biology and immunology of brain tumors, interface of systemic and local (i.e. brain) immune responses, and challenges and hopes in current clinical trials. These illustrate my leadership ability in multi-disciplinary settings and collaboration.
I have also proven myself to be a dedicated mentor for trainees. In the past 5 years, I served as a primary research mentor for 9 pre-doctoral and 12 post-doctoral scholars and 4 clinical fellows as well as 4 junior faculty members. With regard to career development of my former trainees, 9 of my former trainees currently hold academic faculty positions, including the most recent graduate of my lab, Dr. Gary Kohanbash, who currently is an assistant professor at University of Pittsburgh School of Medicine. We maintain a strong commitment to diversity, and 3 of 4 post-doctoral members in our lab are females. My mentorship extends to international young scholars, including ones from underrepresented countries, such as our current research assistant, Naznin Jahan, from Bangladesh.

B. Positions and Honors

Positions and Employment

1996-1997
Visiting Research Associate, Department of Neurosurgery, University of Pittsburgh School of Medicine (UPSOM)
1997-1998
Visiting Research Instructor, Department of Neurosurgery, UPSOM
1998-2001
Research Assistant Professor, Department of Neurosurgery, UPSOM
2001-2006
Tenure Track Assistant Professor, Department of Neurosurgery and Surgery, UPSOM
2004-2014
Co-Program Leader, Brain Tumor Program, University of Pittsburgh Cancer Institute
2007-2008
Tenure Track Associate Professor, Department of Neurosurgery and Surgery, UPSOM
2009-2012
Tenured Associate Professor, Department of Neurosurgery, Surgery and Immunology
2012-2014
Professor, Department of Neurosurgery, Surgery and Immunology UPSOM
2014-present
Adjunct Professor, Department of Neurosurgery, Surgery and Immunology UPSOM
2014-present
Kathleen M. Plant Distinguished Professor in Neurological Surgery at UCSF
2014-present
Director, Brain Tumor Immunotherapy Center at UCSF

Certification and Licensure

1991
Medical License for Japan
2003
Japanese Board of Neurological Surgery
2004
Medical Physician and Surgeon, issued by Pennsylvania Department of State
2015
Special Faculty Permit 2168 from California State Board of Medicine

Other Experience and Professional Memberships

1997 - present
Member, The Society for Neuro-oncology (SNO)
1999 - present
Member, American Association for Cancer Research (AACR)
2009 - 2012
Appointed Councilor, Clinical Immunology Society (CIS)
2010 - present
Elected Member, American Society for Clinical Investigation(ASCI)
2010 - present
Member, Society for Immunotherapy of Cancer (SITC)
2013 - present
Chair of the immunotherapy subgroup at the NCI-sponsored Adult Brain Tumor Consortium
2013 - present
Member, Association for Cancer Immunotherapy (CIMT)
2013 - 2016
Steering Committee member of the Cancer Immunology Working Group in the AACR
2014 - present
Member, Cancer Vaccine Consortium (CVC) in Cancer Research Institute (CRI)
2015 - present
A committee member of Advances in Cancer Immunotherapy in SITC

Awards and Honors and roles on federal government and national organization committees (selected)

2001
Doris Duke Charitable Foundation’s Clinical Scientist Development Award
2003
James S. McDonnell Foundation 21st Century Science Initiative Research Award: Brain Cancer Research
2007
Excellence in Translational Medicine Award 2006-07 from Journal of Translational Medicine
2010
Selected to be a member of the American Society for Clinical Investigation (ASCI)
2010
Team Science Recognition Award by Society for Immunotherapy of Cancer
2009, 2011, 2013 and 2014
Faculty Honoree in the Annual Convocation of University of Pittsburgh
2011 to 2015
NIH Clinical Oncology (CONC) Chartered Member
2016
Makoto Saito Memorial International Contribution Award from Japan Neurosurgical Society

Editorial Board

2004 - present
Journal of Translational Medicine (Senior Monitoring Editor)
2010 - present
Journal of Clinical Immunology
2010 - present
OncoImmunology
2013 - present
Cancer Research
2013 - present
Neuro-Oncology

C. Contribution to Science

  1. 1.Identification of glioma-specific or associated antigen -derived cytotoxic T-lymphocyte (CTL) epitopes and development of targeting strategies, such as chimeric antigen receptor (CAR). The central nervous system (CNS) and the tumors arising therein have been often considered “immunologically privileged.” In fact, when I started the project, there was paucity of information as to glioma associated antigens (GAAs) that can be targeted by peripheral vaccine strategies. To alleviate concerns of auto-immunity against normal CNS cells due to shared antigens between glioma cells and normal CNS cells, we have identified peptides that are overexpressed in glioma cells but not in normal CNS cells. Our seminal discovery of those epitopes was one of the first in the field and opened opportunities to develop GAA-targeting vaccines for gliomas. While these GAAs are non-mutated antigens, we recently identified a novel glioma-specific CTL epitope derived from the K27M missense mutation in histone 3.3, which is found in over 70% of pediatric and young adult midline gliomas. Furthermore, as a novel strategy to target surface antigens, we have developed a lentiviral chimeric antigen receptor (CAR) targeting the glioblastoma-specific antigen EGFRvIII. I have led these projects and collaborated with other international experts in the field.
    • ・hanbash G, Chheda Z, Sidney J, Okada K, Shrivastav S, Carrera DA, Liu S, Jahan N, Mueller S, Pollack IF, Carcaboso AM, Sette A, Hou Y, Okada H: Identification of a novel H3.3.K27M mutation-derived neoantigen epitope and cloning of a specific T-cell receptor for T-cell therapy in gliomas. Neuro-Oncology 18:vi87, (2016)
    • ・hnson LA, Scholler J, Ohkuri T, Kosaka A, Patel PR, McGettigan SE, Nace AK, Dentchev T, Thekkat P, Loew A, Boesteanu AC, Cogdill AP, Chen T, Fraietta JA, Kloss CC, Posey AD, Engels B, Singh R, Ezell T, Idamakanti N, Ramones MH, Li N, Zhou L, Plesa G, Seykora JT, Okada H, June CH, Brogdon JL, Maus MV. Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma. Sci Transl Med. 7(275):275ra22. (2015) PMID: 25696001 PMCID: PMC4467166
    • ・no M, Ohkuri T, Kosaka A, Tanahashi K, June CH, Natsume A and Okada H. Expression of miR-17-92 enhances anti-tumor activity of T-cells transduced with the anti-EGFRvIII chimeric antigen receptor in mice bearing human GBM xenografts. Journal for ImmunoTherapy of Cancer 1:21 (2013) PMID: 24829757 PMCID: PMC4019893
    • ・uchi J, Hatano M, Nishimura F, Zhu X, Dusak JE, Sato H, Pollack IF, Storkus WJ and Okada H. Identification of interleukin-13 receptor alpha2 peptide analogues capable of inducing improved antiglioma CTL responses. Cancer Res. 66(11):5883-91. (2006) PMID: 16740728
  2. 2.Factors and adjuvant that promote homing of T-cells to CNS tumors. Accumulation of effector CTLs is often poor in brain tumors compared with cancer in other organs. We have delineated critical molecular factors that promote the homing of vaccine-induced CTLs to the brain tumor site; an integrin receptor VLA-4 and chemokine CXCL10. We have subsequently found poly-ICLC as an immuno-adjuvant can effectively induce these factors on the CTLs, thereby effectively promoting their migration to CNS tumors in the vaccine recipients. We have also demonstrated critical roles of stimulator of IFN genes (STING) and type-1 interferons for the favorable immunological milieu in gliomas. I have led my team to achieve these discoveries.
    • ・kuri T, Ghosh A, Kosaka A, Zhu J, Ikeura M, David M, Watkins SC, Sarkar SN, Okada H. STING Contributes to Antiglioma Immunity via Triggering Type I IFN Signals in the Tumor Microenvironment. Cancer Immunol Res. 2(12):1199-208 (2014) PMID: 25300859 PMC4258479
    • ・jita M, Scheurer ME, Decker SA, McDonald HA, Kohanbash G, Kastenhumber ER, Kato H, Bondy ML, Ohlfest JR, Okada H. Role of Type-1 Interferons in Anti-Glioma Immunosurveillance - Using Mouse Studies to Guide Examination of Novel Prognostic Markers in Humans. Clin Cancer Res. 16 (13):3409-19 (2010) PMID: 20472682, PMCID: PMC2896455
    • ・jita M, Zhu X, Ueda R, Sasaki K, Kohanbash G, Kastenhuber ER, McDonald HA, Gibson GA, Watkins SC, Muthuswamy R, Kalinski P, and Okada H. Effective immunotherapy against a murine glioma using type-1 polarizing DCs - significant roles of CXCL10. Cancer Res. 69(4):1587-95 (2009). PMID: 19190335
    • ・saki K, Zhu X, Vasquez C, Nishimura F, Dusak JE, Huang J, Fujita M, Wesa A, Potter DM, Walker PR, Storkus WJ, and Okada H. Preferential expression of VLA-4 on Tc1 cells plays a critical role in trafficking into central nervous system tumors. Cancer Res. 67 (13):6451-6458. (2007) PMID: 17616706
  3. 3.Immunotherapy clinical trials. As a clinician–scientist, I have developed a number of investigator-initiated glioma immunotherapy clinical trials and relevant investigational new drug (IND) applications by integrating our own laboratory findings on antigens and adjuvant treatment. I also led an international group of brain tumor immunotherapy experts to develop novel response criteria for brain tumor immunotherapy.
    • ・ada H, Weller M, Huang R, Finocchiaro G, Gilbert MR, Wick W, Ellingson BM, Hashimoto N, Pollack IF, Brandes AA, Franceschi E, Herold-Mende C, Nayak L, Panigrahy A, Pope WB, Prins R, Sampson JH, Wen PY, Reardon DA. Immunotherapy Response Assessment in Neuro-Oncology (iRANO): A Report of the RANO Working Group. Lancet Oncol. 16 (15):e534-42. (2015). PMID: 26545842 PMCID: PMC4638131
    • ・ada H, Butterfield LH, Hamilton RL, Hoji A, Sakaki M, Ahn BJ, Kohanbash G, Drappatz J, Engh J, Amankulor N, Lively MO, Chan MD, Salazar AM, Shaw EG, Potter DM, Lieberman FS. Induction of robust type-I CD8+ T-cell responses in WHO grade 2 low-grade glioma patients receiving peptide-based vaccines in combination with poly-ICLC. Clin Cancer Res. 21(2):286-94. (2015) PMID: 25424847 PMCID: PMC4297523
    • ・llack IF, Jakacki RI, Butterfield LH, Hamilton RL, Panigrahy A, Potter DM, Connelly AK, Dibridge SA, Whiteside TL and Okada H. Antigen-specific immune responses and clinical outcome following vaccination with glioma-associated antigen peptides and Poly-ICLC in children with newly-diagnosed malignant brainstem and non-brainstem gliomas. J. Clin Oncol. 32(19):2050-8. (2014) PMID:24888813, PMCID PMC4067943
    • ・ada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, Mintz AH, Engh JA, Bartlett DL, Brown CK, Zeh H, Holtzman MP, Reinhart TA, Whiteside TL, Butterfield LH, Hamilton RL, Potter DM, Pollack IF, Salazar AM and Lieberman FS. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with α-type-1-polarized dendritic cells and Poly-ICLC in Patients with Recurrent Malignant Glioma. J. Clin Oncol. 29(3):330-6 (2011) PMIS: 21149657, PMCID: PMC305646
  4. 4.The immunological microenvironment of gliomas. Gliomas mediate a variety of immunosuppressive mechanisms to escape from immunological attacks. My team was one of the first to describe myeloid-derived suppressor cells (MDSCs) in gliomas. These cells can comprise up to 30-40% of total cell numbers in a tumor mass, mediating immunosuppression. We have reported the roles of interleukin-4 receptor-α and cyclooxygenase (COX)-2 in immunosuppression by MDSC, as well as macrophage migration inhibitory factor in angiogenesis. Most recently, we reported a novel immunosuppression mechanism induced by mutations of the isocitrate dehydrogenase (IDH)1 or 2 in gliomas. I have led these projects as the PI.
    • ・hanbash G, Carrera DA, Shrivastav S, Ahn BJ, Jahan N, Mazor T, Chheda ZS, Downey KM, Watchmaker PB, Beppler C, Warta R, Amankulor NA, Herold-Mende C, Costello JF and Okada H. IDH mutations suppress STAT1 and CD8+ T-cell accumulation in gliomas. J. Clin Invest (in press).
    • ・stro BA, Flanigan P, Jahangiri A, Hoffman D, Chen W, Kuang R, De Lay M, Yagnik G, Wagner JR, Mascharak S, Sidorov M, Shrivastav S, Kohanbash G, Okada H, Aghi MK. Macrophage migration inhibitory factor downregulation: a novel mechanism of resistance to anti-angiogenic therapy. Oncogene. 2017 Feb 20. [Epub ahead of print] PMID: 28218903
    • ・hanbash G, McKaveney K, Sakaki M, Ueda R, Mintz AH, Amankulor N, Fujita M, Ohlfest JR and Okada H. GM-CSF Promotes the Immunosuppressive Activity of Glioma-Infiltrating Myeloid Cells through Interleukin-4 Receptor-α. Cancer Research 73(21):6413-23 (2013).PMID: 24030977, PMCID: PMC3829000
    • ・jita M, Kohanbash G, Fellows-Mayle W, Hamilton RL, Komohara Y, Decker SA, Ohlfest JR and Okada H. COX-2 blockade suppresses gliomagenesis by inhibiting myeloid-derived suppressor cells. Cancer Res. 71(7):2664-74 (2011) PMID: 21324923, PMCID: PMC3075086
  5. 5.Roles of microRNA in anti-CNS tumor immunity. microRNAs (miR) plays a variety of roles in a cell, but it was not clear how we could utilize miRs to improve cancer immunotherapy. My team pioneered studies on critical modulatory roles of microRNA in immune recognition of cancer cells. These outcomes can be integrated in future CAR therapies. I have led these projects as the PI.
    • ・hanbash G. and Okada H. MicroRNAs and STAT Interplay. Seminars in Cancer Biology 22(1):70-5 (2012) PMID: 22210182 PMCID: PMC3288787
    • ・no M, Ohkuri T, Kosaka A, Tanahashi K, June CH, Natsume A and Okada H. Expression of miR-17-92 enhances anti-tumor activity of T-cells transduced with the anti-EGFRvIII chimeric antigen receptor in mice bearing human GBM xenografts. Journal for ImmunoTherapy of Cancer 1:21 (2013) PMC4019893
    • ・da R, Kohanbash G, Sasaki K, Fujita M, Zhu X, Kastenhuber ER, McDonald HA, Potter DM, Hamilton RL, Lotze MT, Khan SA, Sobol RW, and Okada H. Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1. Proc Natl Acad Sci U S A. 106(26):10746-5, (2009) PMID:19520829, PMCID:PMC2705554.
Complete List of Published Work in MyBibliography:
http://www.ncbi.nlm.nih.gov/sites/myncbi/hideho.okada.1/bibliography/41116326/public/?sort=date&direction=ascending

D. Research Support

Ongoing Research Support

NIH/NINDS R01NS096954  Okada (PI)     05/15/16–03/31/21
Novel K27M Mutation-derived Neoantigen for T Cell Therapy in Gliomas
Goal: To evaluate our main hypothesis that the H3.3.K27M represents a novel, shared neoantigen for effective and safe T-cell-based immunotherapy.
Role: Principal Investigator
NIH/NINDS R21 NS083171  Okada (PI)     09/01/2014-08/31/2017
Novel adoptive transfer therapy for glioma using CAR-transduced Type17 T-cells
Goal: to establish the preclinical feasibility, safety, and efficacy of adoptive cell transfer (ACT) therapy with novel Type17 T-cells transduced with chimeric antigen receptor (CAR) in clinically relevant rodent models.
Role: Principal Investigator
NIH/NINDS R21 NS093654  Okada (PI)     07/01/2015-06/30/2017
Antigens for Molecularly Targeted Vaccines for Progressive Glioma”
Goal: This proposal will pursue the hypothesis that gliomas progressing from low-grade to high-grade glioma express changing profiles of glioma-associated antigens (GAAs) which can be targeted by vaccines.
Role: Principal Investigator
NIH/NCI R21 CA177787  Okada (PI)       09/01/2014-08/31/2017
A Phase I Lysate-based vaccine for LGG patients
Goal: Phase I study to assess a vaccination regime consisting of lysate derived from cultured brain tumor-initiating cells and concurrent topical application of imiquimod in adults with WHO grade II LGGs.
Role: Principal Investigator
NIH/NCI P50CA097257  Berger (PI)        09/01/2015-08/31/2018
Brain Tumor SPORE
Goal: Okada leads Project 4, in which we conduct a pilot, randomized, two arm neoadjuvant vaccine study in HLA-A2+ adults with WHO grade II glioma, for which surgical resection of the tumor is clinically indicated. Co-primary objectives are to determine: 1) the safety of the novel combination of IMA950 peptides and poly-ICLC (Hiltonol) and i.v. administered CDX-1127 (Varlilumab) in the neoadjuvant approach; and 2) whether addition of i.v. CDX-1127 (Varlilumab) increases the response rate and magnitude of T-cell responses (NCT02924038).
Role: Project Leader (Project 4)
NIH/NIBIB R01 EB017271  Ahrens (PI)     09/01/2013-08/31/2017
Measuring Cell Aptosis in Vivo Using Perflurocarbon Labeled Cells and 19F MRI
Goal: To determine if macrophage intracellular pO2 can detect immunoactivity to set the foundation for a broad field of inquiries using novel cell tracking agents to garner information about real-time cell metabolism in vivo.
Role: Consortium PI on subaward from University of California, San Diego
NIH/NCI R01 CA174858  Pollack (PI)      05/06/2013-04/30/2017
Peptide vaccine based immunotherapy for children with recurrent ependymoma
Goal: To determine safety and immunological activities of vaccination using GAA-peptides and poly-ICLC for children with recurrent ependymomas.
Role: Consortium PI on subaward from University of Pittsburgh
NIH/NCI R01 CA178766  Thorne (PI)      07/01/2014-6/30/2019
Creation of Immuno-Oncolytic Viruses for Cancer Therapy
Goal: To develop next generation vectors that act as potent and specific immunotherapeutics.
Role: Consortium PI on subaward from University of Pittsburgh
NIH/NCI R01CA1877219  Pollack (PI)      01/01/16-12/31/20
Peptide vaccine immunotherapy for children with recurrent low-grade glioma
Goal: This is a phase II clinical trial to evaluate the efficacy of vaccines using synthetic peptides encoding glioma-associated antigen-derived epitopes and adjuvant polyICLC in pediatric patients with low-grade glioma.
Role: Subaward Principal Investigator
NIH/NCI R21CA201453  Ronen (PI)       12/01/15-11/30/17
Hyperpolarized arginine imaging of inflammatory cells and their inhibition in GBM
Goal: The goal of this application is to develop and validate a novel noninvasive metabolic imaging approach that informs on arginine metabolism as readout of the immunosuppressive pro-tumoral activity of myeloid-derived suppressor cells (MDSCs) in brain tumors.
Role: Co-Investigator

Recently Completed Research Projects

NIH/NINDS 2R01 NS055140  Okada (PI)     02/15/2011-01/31/2017
Novel Immunotherapy of Glioma using miR-17-92 Transfected T Cells
Goal: To determine the role of miR-17-92 in tumor antigen-specific CD8+ T cells using miR-17-92 transgenic T cells in preclinical models of glioma.
Role: Principal Investigator

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