Hideho Okada, MD, PhD

Professor
Department of Neurological Surgery
+1 415 476-1637
Research Description: 

Dr. Okada is a creative physician-scientist who has developed therapeutic modalities in the laboratory, translated them into clinical protocols, and used his expertise as both scientist and clinician to assess the clinical data from ongoing trials. Dr. Okada's work has consistently focused on immunotherapeutic strategies aimed at a daunting challenge in oncology – malignant brain tumors. Dr. Okada conducted one of the first immune gene therapy trials in patients with malignant glioma. Dr. Okada's success in navigating the detailed regulatory processes required for such trials demonstrates his attention to detail and breadth of knowledge, spanning from basic science to clinical care. Dr. Okada's lab work was the first to identify and fully characterize cytotoxic T-lymphocyte (CTL) epitopes for gliomas. Dr. Okada's seminal discovery of CTL epitopes in glioma-associated antigens and the work on the mechanisms underlying the adjuvant effects of poly-ICLC enabled him to launch novel glioma vaccine trials in combination with poly-ICLC as an adjuvant. These efforts have also been supported by his mechanistic studies delineating the role of an integrin receptor very late activation antigen (VLA)-4 and chemokine CXCL10 in the efficient trafficking of T-cells to brain tumor sites. Dr. Okada has held 10 Investigational New Drug approvals 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. For example, 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 Immunotherapy Response Assessment in Neuro-Oncology (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. Dr. Okada also serves as an Associate Editor for Neuro-Oncology, the most prominent journal for brain tumor research.

Primary Thematic Area: 
Immunology
Secondary Thematic Area: 
Cancer Biology & Cell Signaling
Research Summary: 
Brain Tumor Immunology and Immunotherapy

Websites

Publications: 

FcRn-silencing of IL-12Fc prevents toxicity of local IL-12 therapy and prolongs survival in experimental glioblastoma.

Nature communications

Beffinger M, Schellhammer L, Taskoparan B, Deplazes S, Salazar U, Tatari N, Seehusen F, von Balthazar L, Zinner CP, Spath S, Shekarian T, Ritz MF, McDaid M, Egloff P, Zimmermann I, Okada H, Ward ES, Rohrer J, Seeger MA, Buch T, Hutter G, Vom Berg J

Glioma-neuronal circuit remodeling induces regional immunosuppression.

Nature communications

Nejo T, Krishna S, Yamamichi A, Lakshmanachetty S, Jimenez C, Lee KY, Baker DL, Young JS, Chen T, Phyu SSS, Phung L, Gallus M, Maldonado GC, Okada K, Ogino H, Watchmaker PB, Diebold D, Choudhury A, Daniel AGS, Cadwell CR, Raleigh DR, Hervey-Jumper SL, Okada H

Response Assessment in Neuro-Oncology (RANO) 2009-2025: Broad Scope and Implementation - A Progress Report.

Neuro-oncology

van den Bent MJ, Vogelbaum MA, Cloughesy T, Galldiks N, Albert NL, Tonn JC, Avila E, Fangusaro J, Mirsky D, Sahgal A, Soffietti R, Karschnia P, Mehta M, Kim MM, Boele F, Huse JT, Nayak L, Lim-Fat MJ, le Rhun E, Desjardins A, Lee EQ, Chukwueke U, Koekkoek JAF, Mendoza T, Loughan AR, Budhu JA, Bakas S, Huang RY, Villanueva-Meyer JE, Leone JP, Okada H, Reardon DA, Bi WL, Wen PY, Chang SM

Comparative evaluation of CAR-expressing T-, NK-, NKT-cells, and macrophages in an immunocompetent mouse glioma model.

Neuro-oncology advances

Hatae R, Watchmaker PB, Yamamichi A, Kyewalabye K, Okada K, Phyu S, Goretsky Y, Haegelin J, Pineo-Cavanaugh P, Gallus M, Phung L, Chen T, Long H, Chuntova P, Raulet DH, Terabe M, Okada H