Hideho Okada MD, PhD

Hideho Okada MD, PhD

Professor of Neurological Surgery

Director, UCSF Brain Tumor Immunotherapy Center

Dr. Okada is a physician-scientist focused on immunotherapeutic strategies aimed at malignant brain tumors. He conducted one of the first immune gene therapy trials in patients with malignant glioma. His lab work was also the first to identify and fully characterize cytotoxic T-lymphocyte (CTL) epitopes for gliomas. This seminal discovery of CTL epitopes in glioma-associated antigens and his work on the mechanisms underlying the adjuvant effects of poly-ICLC led to the launch of novel glioma vaccine trials in combination with poly-ICLC as an adjuvant. The first of these – a phase 1 study – has already yielded evidence for the safety of the vaccine and its ability to evoke potent immunological responses as well as clinical activities in some patients. Dr. Okada has also performed mechanistic studies delineating the role of an integrin receptor very late activation antigen (VLA)-4 and chemokine CXCL10 in efficient trafficking of T-cells to brain tumor sites.

In 2010, Dr. Okada was selected to be a member of the American Society for Clinical Investigation, which is an honored society of physician-scientists who translate findings in the laboratory to the advancement of clinical practice.

Education, Training, and Previous Positions

1991: Medical License for Japan
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: Assistant Professor, Department of Neurosurgery and Surgery, UPSOM
2003: Japanese Board of Neurological Surgery
2004: Medical Physician and Surgeon, issued by Pennsylvania Department of State
2004-2014: Co-Program Leader, Brain Tumor Program, University of Pittsburgh Cancer Institute
2007-2008: Associate Professor, Department of Neurosurgery and Surgery, UPSOM
2009-2012: Associate Professor, Department of Neurosurgery, Surgery and Immunology
2012-2014: Professor, Department of Neurosurgery, Surgery and Immunology UPSOM

Selected Honors and Awards

1996: Uehara Memorial Foundation Postdoctoral Scholarship
1998: First Place, Award for Scientific Excellence and Potential, 10th Annual University of Pittsburgh Cancer Institute Scientific Retreat
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
2008: University of Pittsburgh Innovator Award
2009: Faculty Honoree in the Annual Convocation of University of Pittsburgh
2009: Appointed Council in the Clinical Immunology Society
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
2011 and 2013: Faculty Honoree in the Annual Convocation of University of Pittsburgh

Selected Recent Publications

Okada H, Attanucci J, Giezeman-Smits KM, Brissette-Storkus C, Fellows WK, Gambotto A, Pollack LF, Pogue-Geile K, Lotze MT, Bozik ME, Chambers WH. Immunization with an antigen identified by cytokine tumor vaccine-assisted SEREX (CAS) suppressed growth of the rat 9L glioma in vivo. Cancer Res 2001;61(6):2625-31.

Okano F, Storkus WJ, Chambers WH, Pollack IF, Okada H. Identification of a novel HLA-A*0201-restricted, cytotoxic T lymphocyte epitope in a human glioma-associated antigen, interleukin 13 receptor alpha2 chain. Clin Cancer Res 2002;8(9):2851-5.

Okada H, Tsugawa T, Sato H, Kuwashima N, Gambotto A, Okada K, Dusak JE, Fellows-Mayle WK, Papworth GD, Watkins SC, Chambers WH, Potter DM, Storkus WJ, Pollack IF. Delivery of interferon-alpha transfected dendritic cells into central nervous system tumors enhances the antitumor efficacy of peripheral peptide-based vaccines. Cancer Res 2004;64(16):5830-8.

Eguchi J, Kuwashima N, Hatano M, Nishimura F, Dusak JE, Storkus WJ, Okada H. IL-4-transfected tumor cell vaccines activate tumor-infiltrating dendritic cells and promote type-1 immunity. J Immunol. 2005 Jun 1;174(11):7194-201.

Kuwashima N, Nishimura F, Eguchi J, Sato H, Hatano M, Tsugawa T, Sakaida T, Dusak JE, Fellows-Mayle WK, Papworth GD, Watkins SC, Gambotto A, Pollack IF, Storkus WJ, Okada H. Delivery of dendritic cells engineered to secrete IFN-alpha into central nervous system tumors enhances the efficacy of peripheral tumor cell vaccines: dependence on apoptotic pathways. J Immunol 2005;175(4):2730-40.

Nishimura F, Dusak JE, Eguchi J, Zhu X, Gambotto A, Storkus WJ, Okada H. Adoptive transfer of type 1 CTL mediates effective anti-central nervous system tumor response: critical roles of IFN-inducible protein-10. Cancer Res 2006;66(8):4478-87.

Eguchi J, Hatano M, Nishimura F, Zhu X, Dusak JE, Sato H, Pollack IF, Storkus WJ, Okada H. Identification of interleukin-13 receptor alpha2 peptide analogues capable of inducing improved antiglioma CTL responses. Cancer Res 2006;66(11):5883-91.

Sasaki K, Zhu X, Vasquez C, Nishimura F, Dusak JE, Huang J, Fujita M, Wesa A, Potter DM, Walker PR, Storkus WJ, Okada H. Preferential expression of very late antigen-4 on type 1 CTL cells plays a critical role in trafficking into central nervous system tumors. Cancer Res 2007;67(13):6451-8.

Fujita M, Zhu X, Sasaki K, Ueda R, Low KL, Pollack IF, Okada H. Inhibition of STAT3 promotes the efficacy of adoptive transfer therapy using type-1 CTLs by modulation of the immunological microenvironment in a murine intracranial glioma. J Immunol 2008;180(4):2089-98.

Ueda R, Kohanbash G, Sasaki K, Fujita M, Zhu X, Kastenhuber ER, McDonald HA, Potter DM, Hamilton RL, Lotze MT, Khan SA, Sobol RW, 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 2009;106(26):10746-51.

Sasaki K, Kohanbash G, Hoji A, Ueda R, McDonald HA, Reinhart TA, Martinson J, Lotze MT, Marincola FM, Wang E, Fujita M, Okada H. miR-17-92 expression in differentiated T cells - implications for cancer immunotherapy. J Transl Med 2010;8:17.

Fujita M, Zhu X, Ueda R, Sasaki K, Kohanbash G, Kastenhuber ER, McDonald HA, Gibson GA, Watkins SC, Muthuswamy R, Kalinski P, Okada H. Effective immunotherapy against murine gliomas using type 1 polarizing dendritic cells--significant roles of CXCL10. Cancer Res 2009;69(4):1587-95.

Ueda R, Fujita M, Zhu X, Sasaki K, Kastenhuber ER, Kohanbash G, McDonald HA, Harper J, Lonning S, Okada H. Systemic inhibition of transforming growth factor-beta in glioma-bearing mice improves the therapeutic efficacy of glioma-associated antigen peptide vaccines. Clin Cancer Res 2009;15(21):6551-9.

Fujita M, Scheurer ME, Decker SA, McDonald HA, Kohanbash G, Kastenhuber ER, Kato H, Bondy ML, Ohlfest JR, Okada H. Role of type 1 IFNs in antiglioma immunosurveillance--using mouse studies to guide examination of novel prognostic markers in humans. Clin Cancer Res 2010;16(13):3409-19.

Zhu X, Fujita M, Snyder LA, Okada H. Systemic delivery of neutralizing antibody targeting CCL2 for glioma therapy. J Neurooncol 2011;104(1):83-92.

Okada 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, Lieberman FS. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol 2011;29(3):330-6.

Fujita M, Kohanbash G, Fellows-Mayle W, Hamilton RL, Komohara Y, Decker SA, Ohlfest JR, Okada H. COX-2 blockade suppresses gliomagenesis by inhibiting myeloid-derived suppressor cells. Cancer Res 2011;71(7):2664-74.

Ma H, Lu C, Ziegler J, Liu A, Sepulveda A, Okada H, Lentzsch S, Mapara MY. Absence of Stat1 in donor CD4⁺ T cells promotes the expansion of Tregs and reduces graft-versus-host disease in mice. J Clin Invest 2011;121(7):2554-69.

Yeung JT, Hamilton RL, Okada H, Jakacki RI, Pollack IF. Increased expression of tumor-associated antigens in pediatric and adult ependymomas: implication for vaccine therapy. J Neurooncol 2013;111(2):103-11.

Yeung JT, Hamilton RL, Ohnishi K, Ikeura M, Potter DM, Nikiforova MN, Ferrone S, Jakacki RI, Pollack IF, Okada H. LOH in the HLA class I region at 6p21 is associated with shorter survival in newly diagnosed adult glioblastoma. Clin Cancer Res 2013;19(7):1816-26.

Liu Y, Kosaka A, Ikeura M, Kohanbash G, Fellows-Mayle W, Snyder LA, Okada H. Premetastatic soil and prevention of breast cancer brain metastasis. Neuro Oncol 2013;15(7):891-903.

Kohanbash G, McKaveney K, Sakaki M, Ueda R, Mintz AH, Amankulor N, Fujita M, Ohlfest JR, Okada H. GM-CSF promotes the immunosuppressive activity of glioma-infiltrating myeloid cells through interleukin-4 receptor-α. Cancer Res. 2013;73(21):6413-23.

Ohno M, Ohkuri T, Kosaka A, Tanahashi K, June CH, Natsume A, 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. J Immunother Cancer 2013;1:21.

Pollack IF, Jakacki RI, Butterfield LH, Hamilton RL, Panigrahy A, Potter DM, Connelly AK, Dibridge SA, Whiteside TL, Okada H. Antigen-specific immune responses and clinical outcome after vaccination with glioma-associated antigen peptides and polyinosinic-polycytidylic Acid stabilized by lysine and carboxymethylcellulose in children with newly diagnosed malignant brainstem and nonbrainstem gliomas. J Clin Oncol 2014;32(19):2050-8.