Shiga, Japan – April 3, 2023 - Takara Bio Inc., an innovative biotechnology company, announced the submission of a Clinical Trial Application (CTA) to Health Canada and the receipt of the No Objection Letter to initiate a Phase I/Ib clinical trial for CD19 JAK/STAT CAR-T therapy (TBI-2001). Once the necessary steps are taken, the investigator-initiated clinical trial will be started for patients with CD19 positive B-cell lymphoma. The TBI-2001 is the anti-cancer therapeutic product using next-generation chimeric antigen receptor (CAR) technology which has been developed by the collaboration of Takara Bio with Dr. Naoto Hirano, Chair, Immuno-Oncology Program, Associate Director for Research, Tumor Immunotherapy Program, Senior Scientist, Princess Margaret Cancer Centre (PM Cancer Centre) / Professor of Medicine, Department of Immunology, University of Toronto.  


The first CAR-T cell product has been approved in the United States in 2017 based on its high therapeutic efficacy on the treatment of relapsed or refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Several CAR-T cell products are available since then. While CAR-T therapy becomes widely used, a high proportion of relapse remains a clinical challenge and it is due to the low persistency of CAR-T cells.


TBI-2001 is a novel CAR-T cell product expressing a next-generation CAR1 construct which activates a JAK/STAT signal transduction. In the CAR-T cell therapy, it is known that the structure of protein called CAR has an important role to determine the target cancer type and its therapeutic efficacy. TBI-2001 with the new CAR construct has demonstrated the increased proliferation and persistence of T lymphocytes, resulting in the enhanced antitumor activity in preclinical studies2. These results suggest that TBI-2001 has the potential to show the sustained anti-tumor effect and to prevent relapse, which have been issues of CAR-T therapy.


Takara Bio has concluded a patent license agreement for this JAK/STAT cytokine signaling technology3 with University Health Network where PM Cancer Centre belongs, and will investigate the superiority of the JAK/STAT technology over the approved CD19 CAR products.


Takara Bio is dedicated to contribute to good health of humankind by implementing its leading biotechnology.

  1. CAR is the receptor that specifically recognizes tumor antigens, which is genetically engineered to combine the antibody domain derived from an antibody that specifically recognizes tumor antigens and the intracellular signaling domain such as T cell receptors and costimulatory molecules. Most of CAR-T therapies are ex-vivo gene therapy where patient-derived T cells are transduced with CAR genes outside the body and infused back into the patient.   
  2. Kagoya Y, Tanaka S, Guo T, et al. “A novel chimeric antigen receptor containing a JAK-STAT signalling domain mediates superior antitumor effects.” Nat Med., 24: 352-359, 2018
  3. Takara has acquired the exclusive license to use patent technology relating to next-generation CAR-T therapy (April 26, 2019)

[Overview of Clinical Trial]


Phase I/Ib Study of TBI-2001 for Patients with Relapsed or Refractory CD19+ B-cell Lymphoma, Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Clinical Indication

Patients with CD19+ B-cell Lymphoma or CLL/SLL

Primary Objective

To evaluate the safety of TBI-2001 and determine the recommended phase 2 dose (RP2D)

Secondary Objective

To evaluate the efficacy of TBI-2001

Number of trial subjects


Study site

Princess Margaret Cancer Centre

Principal Investigator

Marcus Butler, MD

[Princess Margaret Cancer Centre]


Princess Margaret Cancer Centre


Since 1952


Toronto, Ontario, Canada


The largest cancer center in Canada and specializes in the treatment and research of cancer in collaboration with other institutes including Toronto General Hospital, Toronto Western Hospital and Toronto Rehabilitation Institute. Affiliated with University of Toronto.