Toshi Maruyama, MD, PhD
Chief Scientific Officer and Chief Operations Officer
As COO/CSO, Toshi Maruyama is responsible for research, development, and manufacture of products.
Prior to founding Abwiz Bio, he acquired his skills in phage display in the lab of Dennis Burton at The Scripps Research Institute, La Jolla, CA and has held several senior scientist and management roles at Alexion Antibody Technologies, Calmune, and Nitto Denko Technical, USA.
He has over 30 years of antibody development experience in academia and pharma. Toshi obtained his MD and PhD degree at Tokyo Medical and Dental University.
Toshi Maruyama has spent thirty years getting antibodies out of samples other people could not work with — the bone marrow of Ebola survivors, blood from vaccinated military donors, primary leukemia cells, immunized rabbits. That is the same problem our clients bring us.
Programs he has taken from a difficult sample to a working antibody
Ebola — the first human antibody shown to neutralize the virus
In Dennis Burton’s laboratory at Scripps, phage display libraries were built from the bone marrow of donors who survived the 1995 Ebola outbreak in Kikwit. From those libraries came KZ52, which neutralized Ebola virus at 0.3–0.4 µg/mL. Three years later it was shown to protect animals from lethal challenge when given before exposure — and up to an hour after it. KZ52 became the reference antibody for the field that followed.
Maruyama T, Rodriguez LL, Jahrling PB, Sanchez A, Khan AS, Nichol ST, Peters CJ, Parren PW, Burton DR. Ebola virus can be effectively neutralized by antibody produced in natural human infection. J Virol 1999;73(7):6024–30. PMID 10364354
Parren PW, Geisbert TW, Maruyama T, Jahrling PB, Burton DR. Pre- and postexposure prophylaxis of Ebola virus infection in an animal model by passive transfer of a neutralizing human antibody. J Virol 2002;76(12):6408–12. PMID 12021376
Anthrax — and the cloning method that made it possible
Reaching the rare antibodies in a vaccinated donor’s repertoire needed a cloning method that did not throw most of the repertoire away. He invented one. Libraries built with it from military donors yielded Fabs binding protective antigen at sub-nanomolar affinity, neutralizing anthrax toxin substoichiometrically and protecting rats in vivo. That method is now US Patent 9,890,414 — the WizAmp™ library construction our discovery campaigns still run on, applied since to human, mouse, humanized mouse, marmoset, alpaca, llama and rabbit repertoires.
Wild MA, Xin H, Maruyama T, Nolan MJ, Calveley PM, Malone JD, Wallace MR, Bowdish KS. Human antibodies from immunized donors are protective against anthrax toxin in vivo. Nat Biotechnol 2003;21(11):1305–6. PMID 14555959
Hepatitis C — antibodies broad enough to survive the quasispecies
HCV’s problem is variability: an antibody that works on one isolate meets a swarm of others. Human monoclonals were identified that neutralized genetically diverse isolates and protected against heterologous quasispecies challenge in a liver-chimeric mouse. It is the same problem shape we later solved for SARS-CoV-2 variants — breadth against a moving target.
Law M, Maruyama T, Lewis J, Giang E, Tarr AW, Stamataki Z, Gastaminza P, Chisari FV, Jones IM, Fox RI, Ball JK, McKeating JA, Kneteman NM, Burton DR. Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge. Nat Med 2008;14(1):25–7. PMID 18064037
CD200 — antibodies raised by panning on patient cells
Chronic lymphocytic leukemia cells suppress the immune response through CD200. Rather than a recombinant antigen, the library was panned on primary CLL cells directly. The resulting antibodies blocked the CD200/CD200R interaction and restored the Th1 response in most patient samples tested; the program went on into clinical development. Cell-based panning on native antigen is now one of our standard discovery routes.
McWhirter JR, Kretz-Rommel A, Saven A, Maruyama T, Potter KN, Mockridge CI, Ravey EP, Qin F, Bowdish KS. Antibodies selected from combinatorial libraries block a tumor antigen that plays a key role in immunomodulation. Proc Natl Acad Sci USA 2006;103(4):1041–6. PMID 16418292
SARS-CoV-2 — an antibody re-engineered faster than the virus moved
A rabbit-derived neutralizing clone was humanized, then re-matured with STEM™ each time the variants outran it. The final panel neutralized all 21 variants tested, including eight on which a clinical-stage therapeutic antibody had lost activity. In parallel, two of the antibodies were benchmarked against nearly 400 candidates in the CoVIC global consortium.
Entzminger KC, Fleming JK, Entzminger PD, Espinosa LY, Samadi A, Hiramoto Y, Okumura SCJ, Maruyama T. Rapid engineering of SARS-CoV-2 therapeutic antibodies to increase breadth of neutralization. Antib Ther 2023;6(2):108–118. PMID 37324547
Callaway HM, Hastie KM, et al. (incl. Maruyama T, Okumura CJ). Bivalent intra-spike binding provides durability against emergent Omicron lineages: results from a global consortium. Cell Rep 2023;42(1):112014. PMID 36681898
Positions
| 2012–present | Abwiz Bio, Inc. | Chief Scientific Officer & Chief Operating Officer |
| 2010–2012 | Nitto Denko Technical | Chief Scientist, then Group Leader |
| 2007–2010 | Calmune Corporation | Associate Director, Antibody Technologies |
| 2000–2006 | Alexion Antibody Technologies | Staff Scientist to Principal Scientist |
| 1996–2000 | The Scripps Research Institute | Research Associate, Dennis Burton laboratory |
| 1993–1995 | University of California, San Diego | Postdoctoral Research Fellow |
| 1987–1993 | Tokyo Medical and Dental University | Resident, then medical staff, First Department of Internal Medicine and Medical Research Institute |
Inventions
US 9,890,414 — a library construction method that preserves repertoire diversity from an immune source. The basis of WizAmp™, and of every discovery campaign we run.
US 2022/0372119 A1 — highly specific antibodies to the oxidative-stress marker 8-OHdG, raised by competitive selection against the cross-reactants actually present in urine.
Publication details above verified against PubMed. Full bibliography: NCBI.
Kawade R, Akiba H, Entzminger K, Maruyama T, Okumura CJ, Tsumoto K: Roles of the disulfide bond between the variable and the constant domains of rabbit immunoglobulin kappa chains in thermal stability and affinity. Protein Eng Des Sel 2018; 31: 243-247.
Shimizu H, Nakagawa M, Todaka N, Imaizumi K, Kurosawa Y, Maruyama T, Okumura CJ, Shibata T, Tanaka Y, Sato Y, Ono Y, Akuta T: Improving the quality of a recombinant rabbit monoclonal antibody against PLXDC2 by optimizing transient expression conditions and purification method. Protein Expr Purif 2018; 146: 27-33.
Arakawa T, Kurosawa Y, Storms M, Maruyama T, Okumura CJ, Maluf NK: Biophysical characterization of a model antibody drug conjugate. Drug Discov Ther. 2016; 10: 211-7.
Arakawa T, Kurosawa Y, Storms M, Maruyama T, Okumura CJ, Kita Y: Capto MMC mixed-mode chromatography of murine and rabbit antibodies. Protein Expr Purif. 2016; 127: 105-110.
Hunt AR, Bowen RA, Frederickson S, Maruyama T, Roehrig JT, Blair CD: Treatment of mice with human monoclonal antibody 24h after lethal aerosol challenge with virulent Venezuelan equine encephalitis virus prevents disease but not infection. Virology 2011; 414: 146-52.
Hunt AR, Frederickson S, Maruyama T, Roehrig JT, Blair CD: The First Human Epitope Map of the Alphaviral E1 and E2 Proteins Reveals a New E2 Epitope with Significant Virus Neutralizing Activity. PLo S Negl Trop Dis 2010; 4:e739.
Nelson JD, Kinkead H, Brunel FM, Leaman D, Jensen R, Louis JM, Maruyama T, Bewley CA, Bowdish K, Clore GM, Dawson PE, Frederickson S, Mage RG, Richman DD, Burton DR, Zwick MB: Antibody elicited against the gp41 N-heptad repeat (NHR) coiled-coil can neutralize HIV-1 with modest potency but non-neutralizing antibodies also bind to NHR mimetics. Virology 2008; 377: 170-83.
Siva AC, Wild MA, Kirkland RE, Nolan MJ, Lin B, Maruyama T, Yantiri-Wernimont F, Frederickson S, Bowdish KS, Xin H: Targeting CUB domain-containing protein 1 with a monoclonal antibody inhibits metastasis in a prostate cancer model. Cancer Res 2008; 68: 3579-66.
Law M, Maruyama T, Lewis J, Giang E, Tarr AW, Stamataki Z, Gastaminza P, Chisari FV, Jones IM, Fox RI, Ball JK, McKeating JA, Knetemena NM, Burton DR: Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge. Nature Med 2008; 4: 25-7.
Siva AC, Kirkland RE, Lin B,Maruyama T, McWhirter J, Yantiri-Wernimont F, Bowdish KS, Xin H: Selection of anti-cancer antibodies from combinatorial libraries by whole-cell panning and stringent subtraction with human blood cells. J Immunol Methods 2007; 330: 109-19.
Kretz-Rommel A, Qin F, Dakappagari N, Ravey EP, McWhirter J, Oltean D, Frederickson S,Maruyama T, Wild MA, Nolan M-J, Wu Dayang, Springhorn J, Bowdish KS: CD200 expression on tumor cells suppresses anti-tumor immunity: New approaches to cancer immunotherapy. J Immunol 2007; 178: 5595-605.
McWhirter JR, Kretz-Rommel A, Saven A, Maruyama T, Potter KN, Mockridge CI, Ravey EP, Qin F, Bowdish KS: Antibodies selected from combinatorial libraries block a tumor antigen that plays a key role in immunomodulation. Proc Natl Acad Sci USA 2006; 103: 1041-46.
Dakappagari N, Maruyama T, Renshaw M, Tacken P, Figdor C, Torensma R, Wild MA, Wu D, Bowdish K, Kretz-Rommel A: Internalizing Antibodies to the C-Type Lectins, L-SIGN and DC- SIGN, Inhibit Viral Glycoprotein Binding and Deliver Antigen to Human Dendritic Cells for the Induction of T cell Responses. J Immunol 2006: 176: 426-40.
Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, Liu CC, Maruyama T, Hynes RO, Burton DR, McKeating JA, Rice CM: Complete replication of hepatitis C virus in cell culture. Science 2005; 309: 623-6.
Wild MA, Xin H, Maruyama T, Nolan MJ, Calveley PM, Malone JD, Wallace MR, Bowdish KS: Human antibodies from immunized donors are protective against anthrax toxin in vivo. Nat Biotechnol 2003; 221: 1305-1306.
Meissner F, Maruyama T, Frentsch M, Hessell AJ, Rodriguez LL, Geisbert TW, Jahrling PB, Burton DR, Parren PWHI: Detection of antibodies against the four subtypes of Ebola virus in sera from any species using a novel antibody-phage indicator assay. Virology 2002; 300: 236- 43.
Parren PWHI, Geisbert TW, Maruyama T, Jahrling PB, Burton DR. Pre- and post exposure prophylaxis of Ebola virus infection in an animal model by passive transfer of a neutralizing human antibody. J Virol 2002; 76: 6408-12.
Maruyama T, Rodriguez LL, Jahrling PB, Sanchez A, Khan AS, Nichol ST, Peters CJ, Parren PWHI, Burton DR: Ebola virus can be effectively neutralized by antibody produced in natural human infection. J Virol 1999; 73: 6024-6030.
Maruyama T, Parren PWHI, Sanchez A, Rensink I, Rodriguez LL, Khan AS, Peters CJ, Burton DR: Recombinant human monoclonal antibodies to Ebola virus. J Infect Dis 1999; 179 (Suppl 1): S235-239.
Maruyama T Buchmeier MJ, Parren PWHI, Burton DR: Ebola Virus, Neutrophils, and Antibody Specificity. Science 1998; 282: 845a.
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