CAR

Outline

Chimeric Antigen Receptor (CAR) gene therapy, one of the gene-engineered T-cell therapies, is essentially the same as T-Cell Receptor gene therapy but with a different recombinant receptor structure. CAR gene is artificially constructed by combining a single chain variable fragment derived from antibodies that specifically recognize certain antigens expressed on the surface of malignant cells, and cytoplasmic domain(s) required for lymphocyte activation. The genetically engineered CAR T-lymphocytes can recognize the antigens on the cell surface and attack the malignant cells.
RetroNectin®, a recombinant human fibronectin fragment, used in the manufacturing process, leads to highly efficient gene transduction.

Note : As for RetroNectin® , please refer to the following link below.
https://www.takarabio.com/learning-centers/gene-function/viral-transduction/retronectin-learning-center/technology-overview

CAR T-cell therapy targeting CD19 antigen expressed on the B-cell malignancies such as acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia, and B-cell non Hodgkin lymphoma (B-NHL) has been developed actively in many countries. Takara Bio has been conducting CD19·CAR T-cell therapy targeting relapsed or refractory ALL in collaboration with Otsuka Pharmaceutical Co., Ltd in Japan. Also, we are supporting a clinical research of CD19·CAR T-cell therapy targeting B-NHL, conducted by Jichi Medical University.

Mode of action

Redirected CAR T-lymphocytes to the surface antigen of malignant cells exert cytotoxicity by the following steps:

  • Tumor antigen specific CAR is expressed on the cell surface by transducing CAR gene into T-lymphocytes.
  • The expressed CAR molecules recognize antigens on the target malignant cells. Subsequently, signal transduction is activated within gene-transduced T-lymphocytes, and antitumor activity to malignant cells is exerted by release of cytotoxic molecules.
Reference information
Articles

Ohmine K. CD19-targeted CAR T-cell Therapy for Acute Lymphoblastic Leukemia Hematology Frontier. 24:4;98-104,2014. [Article in Japanese]

Information of academic conferences
Conference Tittle
The 21st Japan Society of Gene and Cell Therapy
July 24 - 26, 2015
Osaka, Japan
(Click here for presented data)
Best CAR design based on the analysis if ligand-independent activation of CD19-CAR T cells.
American Society of Gene & Cell Therapy 18th Annual Meeting
May 13 - 16, 2015
New Orleans, U.S.A
(Click here for presented data)
Detail analysis of non-specific activation of CD19 CAR-T cell caused by CD19 CAR design for effective and safe CAR-T cell immunotherapy.

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