Research Summary

Dr. Okada is a Professor of Neurosurgery at the University of California, San Francisco, and a member of Parker Institute for Cancer Immunotherapy. Trained as a physician-scientist, Dr. Okada has been dedicated to understanding the immune mechanisms in brain tumors and developing novel immunotherapy strategies for brain tumor patients for over 25 years. His team was the first to discover cytotoxic T lymphocyte (CTL) epitopes in glioma-associated antigens. Dr. Okada also found critical roles for the integrin receptor very late activation antigen (VLA)-4 and the chemokine CXCL10 in facilitating the entry of CTLs to the brain tumor site. Dr. Okada has translated these discoveries and developed a total of 8 investigational new drug (IND) applications that the FDA approved for early-phase clinical trials, including genetically engineered glioma vaccines and T cell receptor (TCR)- or chimeric antigen receptor (CAR)-transduced T cell therapy in both adult and pediatric patients. One of his vaccine studies evaluating the H3.3K27M mutation-derived neoantigen (NCT02960230) is open at 14 international sites. In addition, Dr. Okada has developed a chimeric antigen receptor (CAR) against epidermal growth factor receptor (EGFR)vIII, which has been evaluated in patients with EGFRvIII+ GBM. Recently, Dr. Okada developed a novel synNotch-primed CAR system with Dr. Wendell Lim to overcome the antigen-heterogeneity, off-tumor toxicity, and T-cell exhaustion issues. Dr. Okada’s team has also pioneered discoveries of novel immunoregulatory mechanisms in gliomas, such as one mediated by myeloid-derived suppressor cells (MDSC) and mutations of the isocitrate dehydrogenase (IDH)1 and IDH2. As a thought leader, to improve radiologic evaluation criteria for patients undergoing immunotherapy, Dr. Okada led an international group of brain tumor immunotherapy experts to develop novel iRANO criteria. Dr. Okada is an elected member of the American Society for Clinical Investigation (2010-present), an honored society for physicians who promote laboratory science to the clinic.

Research Funding

  • December 15, 2017 - November 30, 2025 - Preclinical development of breakthrough immunotherapy for brain tumors , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R35NS105068
  • July 1, 2018 - June 30, 2023 - Glioma immunotherapy targeting IDH mutation-derived epitope and immunosuppression , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA222965
  • May 15, 2016 - March 31, 2021 - Novel K27M Mutation-derived Neoantigen for T Cell Therapy in Gliomas , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01NS096954
  • February 14, 2019 - January 31, 2021 - Pilot randomized neoadjuvant vaccine with CD27-costimulation in low-grade glioma , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA233856
  • July 1, 2015 - June 30, 2018 - Antigens for Molecularly Targeted Vaccines for Progressive Glioma , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21NS093654
  • September 25, 2014 - August 31, 2017 - Phase I Vaccine Study using Brain Tumor Initiating Cells in WHO Grade II Gliomas , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA177787
  • September 15, 2014 - August 31, 2017 - Novel adoptive transfer therapy for glioma using CAR-transduced Type17 T-cells , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21NS083171
  • April 1, 2006 - January 31, 2017 - Novel Immunotherapy of Glioma using miR-17-92 Transfected T Cells , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01NS055140
  • April 27, 2009 - March 31, 2014 - Directing Tumor-specific T cells to Tumors , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P01CA132714
  • December 1, 2000 - February 28, 2014 - Novel Strategies for Brain Tumor Therapy , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P01NS040923
  • March 1, 2010 - February 28, 2013 - Peptide-Based Vaccine Therapy for Childhood Malignant Gliomas , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA149872
  • July 1, 2009 - June 30, 2012 - A Bi-Institutional Pilot Study of Vaccinations for Patients with Low Grade Glioma , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA133859
  • May 23, 2005 - March 31, 2011 - Cytokine Gene Therapy of Cancer - Preclinical Studies , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P01CA100327
  • January 1, 2007 - December 31, 2009 - Vaccination With Peptide-loaded alphaDC1s For Malignant Gliomas , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA117152
  • December 1, 1978 - March 31, 2009 - General Clinical Research Center , Co-Investigator . Sponsor: NIH, Sponsor Award ID: M01RR000056

Education

Nagoya University School of Medicine-Japan, M.D., 1991, Medicine
Nagoya University School of Medicine-Japan, Ph.D., 1996, Medicine
Handa Municipal Hospital-Japan, Internship, Residency, 1991-1992
Nagoya University School of Medicine-Japan, Residency, 1992-1996, Neurosurgery

Honors & 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
  • 2010
    Team Science Recognition Award by Society for Immunotherapy of Cancer
  • 2011
    Faculty Honoree in the Annual Convocation of University of Pittsburgh

Selected Publications

  1. Simic MS, Watchmaker PB, Gupta S, Wang Y, Sagan SA, Duecker J, Shepherd C, Diebold D, Pineo-Cavanaugh P, Haeglin J, Zhu R, Ng B, Yu W, Tonai Y, Cardarelli L, Reddy NR, Sidhu SS, Troyanskaya O, Hauser SL, Wilson MR, Zamvil SS, Okada H# and Lim WA# (# co-corresponding authors). Programming Tissue-Sensing T Cells That Deliver Therapies To The Brain”  Journal and Citation: Science  (in press)
  2. Montoya M, Collins SA, Chuntova P, Patel TS, Nejo T, Yamamichi A, Kasahara N, and Okada H. IRF8-driven reprogramming of the immune microenvironment enhances anti-tumor adaptive immunity and reduces immunosuppression in murine glioblastoma. Neuro Oncol. 2024 (in press) (Hideho Okada as the corresponding author)
  3. Hou AJ, Shih RM, Uy ER, Shafer A, Chang ZL, Comin-Anduix B, Guemes M, Galic Z, Phyu S, Okada H, Grausam KB, Breunig JJ, Brown CE, Nathanson DA, Prins RM, and Chen YY. IL-13Rα2/TGF-β bispecific CAR-T cells counter TGF-β-mediated immune suppression and potentiate anti-tumor responses in glioblastoma. Neuro Oncol. 2024 (in press).
  4. Nejo T, Wang L, Leung KK, Wang A, Lakshmanachetty S, Gallus M, Kwok DW, Hong C, Chen LH, Carrera DA, Zhang MY, Stevers NO, Maldonado GC, Yamamichi A, Watchmaker PB, Naik A, Shai A, Phillips JJ, Chang SM, Wiita AP, Wells JA, Costello JF, Diaz AA, Okada H. Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma. Sci Rep. 2024 03 16; 14(1):6362. PMID: 38493204. PMCID: PMC10944514 (Hideho Okada as the corresponding author)
  5. Hatae R, Kyewalabye K, Yamamichi A, Chen T, Phyu S, Chuntova P, Nejo T, Levine LS, Spitzer MH, Okada H. Enhancing CAR-T cell metabolism to overcome hypoxic conditions in the brain tumor microenvironment. JCI Insight. 2024 Feb 22. PMID: 38386420 (Hideho Okada as the corresponding author)
  6. Saijo A, Ogino H, Butowski NA, Tedesco MR, Gibson D, Watchmaker PB, Okada K, Wang AS, Shai A, Salazar AM, Molinaro AM, Rabbitt JE, Shahin M, Perry A, Clarke JL, Taylor JW, Daras M, Oberheim Bush NA, Hervey-Jumper SL, Phillips JJ, Chang SM, Hilf N, Mayer-Mokler A, Keler T, Berger MS, Okada H. A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas. Neuro Oncol. 2024 Feb 02; 26(2):335-347. PMID: 37758193. PMCID: PMC10836773 (Hideho Okada as the corresponding author)
  7. Mathur R, Wang Q, Schupp PG, Nikolic A, Hilz S, Hong C, Grishanina NR, Kwok D, Stevers NO, Jin Q, Youngblood MW, Stasiak LA, Hou Y, Wang J, Yamaguchi TN, Lafontaine M, Shai A, Smirnov IV, Solomon DA, Chang SM, Hervey-Jumper SL, Berger MS, Lupo JM, Okada H, Phillips JJ, Boutros PC, Gallo M, Oldham MC, Yue F, Costello JF. Glioblastoma evolution and heterogeneity from a 3D whole-tumor perspective. Cell. 2024 01 18; 187(2):446-463.e16. PMID: 38242087. PMCID: PMC10832360
  8. Kwok DW, Stevers NO, Nejo T, Chen LH, Etxeberria I, Jung J, Okada K, Cove MC, Lakshmanachetty S, Gallus M, Barpanda A, Hong C, Chan GKL, Wu SH, Ramos E, Yamamichi A, Liu J, Watchmaker P, Ogino H, Saijo A, Du A, Grishanina N, Woo J, Diaz A, Chang SM, Phillips JJ, Wiita AP, Klebanoff CA, Costello JF*, Okada H*. Tumor-wide RNA splicing aberrations generate immunogenic public neoantigens. bioRxiv [Preprint]. 2023 Oct 20:2023.10.19.563178. PMID: 37904942  PMCID: PMC10614978 * Co-corresponding authors.
  9. Lee J, Nicosia M, Hong ES, Silver DJ, Li C, Bayik D, Watson DC, Lauko A, Kay KE, Wang SZ, Johnson S, McGraw M, Grabowski MM, Kish DD, Desai AB, Goodman WA, Cameron SJ, Okada H, Valujskikh A, Fairchild RL, Ahluwalia MS, Lathia JD. Sex-Biased T-cell Exhaustion Drives Differential Immune Responses in Glioblastoma. Cancer Discov. 2023 09 06; 13(9):2090-2105. PMID: 37378557. PMCID: PMC10481130
  10. Nejo T, Krishna S, Jimenez C, Yamamichi A, Young JS, Lakshmanachetty S, Chen T, Phyu SSS, Ogino H, Watchmaker P, Diebold D, Choudhury A, Daniel AGS, Raleigh DR, Hervey-Jumper SL, Okada H. Glioma-neuronal circuit remodeling induces regional immunosuppression. bioRxiv. 2023 Aug 06. PMID: 37577659. PMCID: PMC10418167 (Hideho Okada as the corresponding author)
  11. Gallus M, Roll W, Dik A, Barca C, Zinnhardt B, Hicking G, Mueller C, Naik VN, Anstötz M, Krämer J, Rolfes L, Wachsmuth L, Pitsch J, van Loo KMJ, Räuber S, Okada H, Wimberley C, Strippel C, Golombeck KS, Johnen A, Kovac S, Groß CC, Backhaus P, Seifert R, Lewerenz J, Surges R, Elger CE, Wiendl H, Ruck T, Becker AJ, Faber C, Jacobs AH, Bauer J, Meuth SG, Schäfers M, Melzer N. Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell-mediated limbic encephalitis. Sci Adv. 2023 06 09; 9(23):eabq7595. PMID: 37294768. PMCID: PMC10256169
  12. Carnevale J, Shifrut E, Kale N, Nyberg WA, Blaeschke F, Chen YY, Li Z, Bapat SP, Diolaiti ME, O'Leary P, Vedova S, Belk J, Daniel B, Roth TL, Bachl S, Anido AA, Prinzing B, Ibañez-Vega J, Lange S, Haydar D, Luetke-Eversloh M, Born-Bony M, Hegde B, Kogan S, Feuchtinger T, Okada H, Satpathy AT, Shannon K, Gottschalk S, Eyquem J, Krenciute G, Ashworth A, Marson A. RASA2 ablation in T cells boosts antigen sensitivity and long-term function. Nature. 2022 09; 609(7925):174-182. PMID: 36002574. PMCID: PMC9433322
  13. Chuntova P, Yamamichi A, Chen T, Narayanaswamy R, Ronseaux S, Hudson C, Tron AE, Hyer ML, Montoya M, Mende AL, Nejo T, Downey KM, Diebold D, Lu M, Nicolay B, Okada H. Inhibition of D-2HG leads to upregulation of a proinflammatory gene signature in a novel HLA-A2/HLA-DR1 transgenic mouse model of IDH1R132H-expressing glioma. J Immunother Cancer. 2022 05; 10(5). PMID: 35606087. PMCID: PMC9174833 (Hideho Okada as the corresponding author)
  14. Ogino H, Taylor JW, Nejo T, Gibson D, Watchmaker PB, Okada K, Saijo A, Tedesco MR, Shai A, Wong CM, Rabbitt JE, Olin MR, Moertel CL, Nishioka Y, Salazar AM, Molinaro AM, Phillips JJ, Butowski NA, Clarke JL, Oberheim Bush NA, Hervey-Jumper SL, Theodosopoulos P, Chang SM, Berger MS, Okada H. Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas. J Clin Invest. 2022 02 01; 132(3). PMID: 34882581. PMCID: PMC8803342 (Hideho Okada as the corresponding author)
  15. Chuntova P, Hou Y, Naka R, Yamamichi A, Chen T, Goretsky Y, Hatae R, Nejo T, Kohanbash G, Mende AL, Montoya M, Downey KM, Diebold D, Skinner J, Liang HE, Schwer B, Okada H. Novel EGFRvIII-CAR transgenic mice for rigorous preclinical studies in syngeneic mice. Neuro Oncol. 2021 Aug 04. PMID: 34347086 (Hideho Okada as the corresponding author)
  16. Simonds EF, Lu ED, Badillo O, Karimi S, Liu EV, Tamaki W, Rancan C, Stultz J, Sinha M, McHenry LK, Nasholm NM, Chuntova P, Sundström A, Genoud V, Shahani SA, Wang LD, Brown CE, Walker PR, Swartling FJ, Fong L, Okada H*, WeissWA* and Hellström M*. Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma. J Immunother Cancer (2021). Jun;9(6):e002181 PMID: 34083417 PMCID: PMC8183210. * co-corresponding authors
  17. Choe JH, Watchmaker PB, Simic MS, Gilbert RD, Li AW, Krasnow NA, Carrera DA, Yu W, Downey KM, Celli A, Cho J, Briones JD, Dannenfelser R, Cardarelli L, Sidhu SS, Roybal KT*, Okada H*, Lim WA*: Multi-antigen recognition circuits overcome challenges of specificity, heterogeneity, and durability in T cell therapy for glioblastoma. Science Translational Medicine. (2021) Apr 28;13(591):eabe7378. PMID: 33910979 PMCID: PMC8362330  * co-corresponding authors.
  18. Ohkuri T, Kosaka A, Ikeura M, Salazar AM, Okada H. IFN-γ- and IL-17-producing CD8+ T (Tc17-1) cells in combination with poly-ICLC and peptide vaccine exhibit antiglioma activity. J Immunother Cancer. 2021 Jun; 9(6). PMID: 34193567. PMCID: PMC8246372 (Hideho Okada as the corresponding author)
  19. Wang L, Shamardani K, Babikir H, Catalan F, Nejo T, Chang S, Phillips JJ, Okada H, Diaz AA. The evolution of alternative splicing in glioblastoma under therapy. Genome Biol. 2021 Jan 26; 22(1):48. PMID: 33499924. PMCID: PMC7835670
  20. Mueller S, Taitt JM, Villanueva-Meyer JE, Bonner ER, Nejo T, Lulla RR, Goldman S, Banerjee A, Chi SN, Whipple NS, Crawford JR, Gauvain K, Nazemi KJ, Watchmaker PB, Almeida ND, Okada K, Salazar AM, Gilbert RD, Nazarian J, Molinaro AM, Butterfield LH, Prados MD, Okada H. Mass cytometry detects H3.3K27M-specific vaccine responses in diffuse midline glioma. J Clin Invest. 2020 Dec 01; 130(12):6325-6337. PMID: 32817593. PMCID: PMC7685729 (Hideho Okada as the corresponding author)

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