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

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. Chheda ZS, Mueller S, Hegde B, Yamamichi A, Butterfield LH, Okada H. Correspondence on 'H3.3K27M mutation is not a suitable target for immunotherapy in HLA-A2+ patients with diffuse midline glioma' by Immisch et al. J Immunother Cancer. 2023 Mar; 11(3).  View on PubMed
  2. Panigrahy A, Jakacki RI, Pollack IF, Ceschin R, Okada H, Nelson MD, Kohanbash G, Dhall G, Bluml S. Magnetic Resonance Spectroscopy Metabolites as Biomarkers of Disease Status in Pediatric Diffuse Intrinsic Pontine Gliomas (DIPG) Treated with Glioma-Associated Antigen Peptide Vaccines. Cancers (Basel). 2022 Dec 05; 14(23).  View on PubMed
  3. 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.  View on PubMed
  4. Shin J, Parker MFL, Zhu I, Alanizi A, Rodriguez CI, Liu R, Watchmaker PB, Kalita M, Blecha J, Luu J, Wright B, Lapi SE, Flavell RR, Okada H, Tlsty TD, Roybal KT, Wilson DM. Antigen-Dependent Inducible T-Cell Reporter System for PET Imaging of Breast Cancer and Glioblastoma. J Nucl Med. 2023 01; 64(1):137-144.  View on PubMed
  5. Watchmaker PB, Colton M, Pineo-Cavanaugh PL, Okada H. Future development of chimeric antigen receptor T cell therapies for patients suffering from malignant glioma. Curr Opin Oncol. 2022 11 01; 34(6):661-669.  View on PubMed
  6. 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. 2022 06 15; 132(12).  View on PubMed
  7. Brown CE, Bucktrout S, Butterfield LH, Futer O, Galanis E, Hormigo A, Lim M, Okada H, Prins R, Marr SS, Tanner K. The future of cancer immunotherapy for brain tumors: a collaborative workshop. J Transl Med. 2022 05 23; 20(1):236.  View on PubMed
  8. 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).  View on PubMed
  9. 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. 2022 02 01; 24(2):259-272.  View on PubMed
  10. 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).  View on PubMed
  11. Haddad AF, Young JS, Oh JY, Okada H, Aghi MK. The immunology of low-grade gliomas. Neurosurg Focus. 2022 02; 52(2):E2.  View on PubMed
  12. Hwang EI, Sayour EJ, Flores CT, Grant G, Wechsler-Reya R, Hoang-Minh LB, Kieran MW, Salcido J, Prins RM, Figg JW, Platten M, Candelario KM, Hale PG, Blatt JE, Governale LS, Okada H, Mitchell DA, Pollack IF. The current landscape of immunotherapy for pediatric brain tumors. Nat Cancer. 2022 01; 3(1):11-24.  View on PubMed
  13. Simonds EF, Lu ED, Badillo O, Karimi S, Liu EV, Tamaki W, Rancan C, Downey KM, 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, Weiss WA, Hellström M. Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma. J Immunother Cancer. 2021 06; 9(6).  View on PubMed
  14. 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 06; 9(6).  View on PubMed
  15. Choe JH, Watchmaker PB, Simic MS, Gilbert RD, Li AW, Krasnow NA, Downey KM, Yu W, Carrera DA, Celli A, Cho J, Briones JD, Duecker JM, Goretsky YE, Dannenfelser R, Cardarelli L, Troyanskaya O, Sidhu SS, Roybal KT, Okada H, Lim WA. SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma. Sci Transl Med. 2021 04 28; 13(591).  View on PubMed
  16. Chuntova P, Chow F, Watchmaker PB, Galvez M, Heimberger AB, Newell EW, Diaz A, DePinho RA, Li MO, Wherry EJ, Mitchell D, Terabe M, Wainwright DA, Berzofsky JA, Herold-Mende C, Heath JR, Lim M, Margolin KA, Chiocca EA, Kasahara N, Ellingson BM, Brown CE, Chen Y, Fecci PE, Reardon DA, Dunn GP, Liau LM, Costello JF, Wick W, Cloughesy T, Timmer WC, Wen PY, Prins RM, Platten M, Okada H. Unique challenges for glioblastoma immunotherapy-discussions across neuro-oncology and non-neuro-oncology experts in cancer immunology. Meeting Report from the 2019 SNO Immuno-Oncology Think Tank. Neuro Oncol. 2021 03 25; 23(3):356-375.  View on PubMed
  17. Mende AL, Schulte JD, Okada H, Clarke JL. Current Advances in Immunotherapy for Glioblastoma. Curr Oncol Rep. 2021 01 26; 23(2):21.  View on PubMed
  18. 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 01 26; 22(1):48.  View on PubMed
  19. Chapelin F, Leach BI, Chen R, Lister D, Messer K, Okada H, Ahrens ET. Assessing Oximetry Response to Chimeric Antigen Receptor T-cell Therapy against Glioma with 19F MRI in a Murine Model. Radiol Imaging Cancer. 2021 01; 3(1):e200062.  View on PubMed
  20. Nair S, Mazzoccoli L, Jash A, Govero J, Bais SS, Hu T, Fontes-Garfias CR, Shan C, Okada H, Shresta S, Rich JN, Shi PY, Diamond MS, Chheda MG. Zika virus oncolytic activity requires CD8+ T cells and is boosted by immune checkpoint blockade. JCI Insight. 2021 01 11; 6(1).  View on PubMed

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