Takamitsu Hattori

At A Glance

• We develop innovative antibody‑based cancer therapeutics and molecular tools to improve treatment outcomes and accelerate biomedical research.
• We integrate synthetic design, directed evolution, and mechanism‑based engineering to generate antibodies with enhanced potency and target selectivity.
• We engineer antibodies into diverse anti‑cancer modalities, including bispecific T‑cell engagers, antibody-drug conjugates (ADCs), and multivalent antibody constructs.
• Building on our discovery of unconventional antigen‑binding modes, we are establishing a platform for generating high‑performance antibodies against challenging targets such as post‑translational modifications.

Short Bio

Dr. Takamitsu Hattori is a Scientist at Princess Margaret Cancer Centre. His research focuses on the development of innovative antibody‑based cancer therapeutics and molecular tools through advanced antibody engineering. He received his PhD in Molecular Engineering from Tohoku University and completed postdoctoral training in protein engineering at the University of Chicago. Following a short research period at Tohoku University, he continued his work at the NYU Grossman School of Medicine and the Laura and Isaac Perlmutter Cancer Center before joining his current institute.

Research Synopsis

Developing Next-Generation Cancer Therapeutic Agents
Antibody‑based therapies, including biologics and immunotherapies, have transformed cancer treatment, yet major challenges remain, such as on‑target off‑tumor toxicity, immunosuppressive tumor microenvironments, tumor heterogeneity, immune‑cold tumors, and therapeutic resistance. By integrating our expertise in protein engineering, structure‑guided design, and mechanism‑based strategies, and through interdisciplinary collaborations with researchers and clinicians both within and outside the institute, we aim to develop innovative therapeutic agents that overcome these limitations. In particular, our prior discoveries of unconventional antibody binding mechanisms have revealed new principles of molecular recognition, which we leverage to rationally design antibody‑based therapeutics with enhanced specificity, affinity, and functionality.

Developing Novel Affinity Reagents and Molecular Tools for Cancer Research and Diagnosis
Antibody reagents are indispensable for biomedical and cancer research, yet poor reagent performance and lot-to-lot variability remain major obstacles, especially for challenging targets such as post-translational modifications. Our goal is to engineer high-performance recombinant antibodies against these difficult but biomedically critical targets, thereby accelerating fundamental discoveries and translational advances in biomedical and cancer research. We further aim to transform these antibodies into highly specific and versatile molecular tools for biosensing, imaging, and diagnostic applications, expanding their utility beyond conventional reagent use.

Recent Publications

Bossowski JP, Pillai R, Kilian J, Wong Lau A, Nakamura M, Rashidfarrokhi A, Hao Y, Li R, Wu K, Hattori T, Glasser E, Koide A, Wang L, Moreira AL, Hajdu C, Rajalingam S, LeBoeuf SE, Le H, Lee S, Oh JW, Joe C, Kim H, Ock CY, Lee SH, Wang H, Patel AAH, Sayin VI, Tsirigos A, Wong KK, Koralov SB, Pende M, Sánchez-Rivera FJ, Simeone DM, Zervantonakis IK, Koide S, Papagiannakopoulos T. The integrated stress response promotes immune evasion through lipocalin 2. Nature, 2026 online ahead of print.

Maso L, Mosure SA, Rodriguez-Aponte SA, Pizzo A, Mensah DN, Southard M, Sze S, Ahmed T, Vash B, Hattori T, Rajak E, Koide A, Neel BG, Koide S, Liu W, Toenjes ST, Jardine PDS, Chopra R, Rader C, Stopfer LE. Engineered antibodies that stabilize drug-modified KRAS^G12C neoantigens enable selective and potent cross-HLA immunotherapy. Nat Commun. 2025 Dec 17;16(1):11264.

Hattori T, Wang M, Corrado AD, Gross S, Fang M, Bang I, Roy N, Berezniuk I, Donaldson H, Groff K, Ravn-Boess N, Koide A, Placantonakis DG, Park CY, Koide S. Engineering antibody-drug conjugates targeting an adhesion GPCR, CD97. Proc Natl Acad Sci U S A. 2025 Oct 7;122(40):e2516627122.

Maso L, Rajak E, Hattori T, Hu Z, Koide A, Neel BG, Koide S. Generation of actionable, cancer-specific neoantigens from KRAS(G12C) with adagrasib. Proc Natl Acad Sci U S A. 2025 Aug 5;122(31):e2509012122.

Bang I, Hattori T, Leloup N, Corrado A, Nyamaa A, Koide A, Geles K, Buck E, Koide S. Selective targeting of oncogenic hotspot mutations of the HER2 extracellular domain. Nat Chem Biol. 2025 May;21(5):706-715.

Hirose T, Nakazawa H, Hattori T, Ishigaki Y, Umetsu M. A Strategy to Develop Zirconia Nanoparticle-Binding Antibodies That Can Easily Cross-Link Nanoparticles by Grafting Even Insoluble Functional Peptides. Langmuir. 2025 Mar 25;41(11):7225-7234.

Riso M, Shah RN, Koide A, Ruthenburg AJ, Koide S, Hattori T. Binding mode-guided development of high-performance antibodies targeting site-specific posttranslational modifications. Proc Natl Acad Sci U S A. 2025 Jan 7;122(1):e2411720121.

Maso L, Rajak E, Bang I, Koide A, Hattori T, Neel BG, Koide S. Molecular basis for antibody recognition of multiple drug-peptide/MHC complexes. Proc Natl Acad Sci U S A. 2024 May 28;121(22):e2319029121.

Ravn-Boess N, Roy N, Hattori T, Bready D, Donaldson H, Lawson C, Lapierre C, Korman A, Rodrick T, Liu E, Frenster JD, Stephan G, Wilcox J, Corrado AD, Cai J, Ronnen R, Wang S, Haddock S, Sabio Ortiz J, Mishkit O, Khodadadi-Jamayran A, Tsirigos A, Fenyö D, Zagzag D, Drube J, Hoffmann C, Perna F, Jones DR, Possemato R, Koide A, Koide S, Park CY, Placantonakis DG. The expression profile and tumorigenic mechanisms of CD97 (ADGRE5) in glioblastoma render it a targetable vulnerability. Cell Rep. 2023 Nov 28;42(11):113374.

Akkapeddi P, Hattori T, Khan I, Glasser E, Koide A, Ketavarapu G, Whaby M, Zuberi M, Teng KW, Lefler J, Maso L, Bang I, Ostrowski MC, O'Bryan JP, Koide S. Exploring switch II pocket conformation of KRAS(G12D) with mutant-selective monobody inhibitors. Proc Natl Acad Sci U S A. 2023 Jul 11;120(28):e2302485120.

Hattori T, Maso L, Araki KY, Koide A, Hayman J, Akkapeddi P, Bang I, Neel BG, Koide S. Creating MHC-Restricted Neoantigens with Covalent Inhibitors That Can Be Targeted by Immune Therapy. Cancer Discov. 2023 Jan 9;13(1):132-145.

Romero LA, Hattori T, Ali MAE, Ketavarapu G, Koide A, Park CY, Koide S. High-valency Anti-CD99 Antibodies Toward the Treatment of T Cell Acute Lymphoblastic Leukemia. J Mol Biol. 2022 Mar 15;434(5):167402.

Oury J, Zhang W, Leloup N, Koide A, Corrado AD, Ketavarapu G, Hattori T, Koide S, Burden SJ. Mechanism of disease and therapeutic rescue of Dok7 congenital myasthenia. Nature. 2021 Jul;595(7867):404-408.

Teng KW, Tsai ST, Hattori T, Fedele C, Koide A, Yang C, Hou X, Zhang Y, Neel BG, O'Bryan JP, Koide S. Selective and noncovalent targeting of RAS mutants for inhibition and degradation. Nat Commun. 2021 May 11;12(1):2656.

Noval MG, Kaczmarek ME, Koide A, Rodriguez-Rodriguez BA, Louie P, Tada T, Hattori T, Panchenko T, Romero LA, Teng KW, Bazley A, de Vries M, Samanovic MI, Weiser JN, Aifantis I, Cangiarella J, Mulligan MJ, Desvignes L, Dittmann M, Landau NR, Aguero-Rosenfeld M, Koide S, Stapleford KA. Antibody isotype diversity against SARS-CoV-2 is associated with differential serum neutralization capacities. Sci Rep. 2021 Mar 10;11(1):5538.

Hattori T, Koide A, Panchenko T, Romero LA, Teng KW, Corrado AD, Koide S. Multiplex bead binding assays using off-the-shelf components and common flow cytometers. J Immunol Methods. 2021 Mar;490:112952.

Hattori T, Koide A, Noval MG, Panchenko T, Romero LA, Teng KW, Tada T, Landau NR, Stapleford KA, Koide S. The ACE2-binding Interface of SARS-CoV-2 Spike Inherently Deflects Immune Recognition. J Mol Biol. 2021 Feb 5;433(3):166748.

Fedele C, Li S, Teng KW, Foster CJR, Peng D, Ran H, Mita P, Geer MJ, Hattori T, Koide A, Wang Y, Tang KH, Leinwand J, Wang W, Diskin B, Deng J, Chen T, Dolgalev I, Ozerdem U, Miller G, Koide S, Wong KK, Neel BG. SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling. J Exp Med. 2021 Jan 4;218(1):e20201414.

Graduate Students

TBD