Japan Tiissue Engineering, Naagoya Univversity, andd Shinshu Universityysign paten
nt license agreement
afor
f the dev
velopment of a low-co
ost manufaacturing tecchnology forfautologous
as CAR-T ce
ell therapy with enhan
nced targe
eting efficie
ency againsst CD 19-positive acu
ute
lymph
hoblastic leeukemia
June 21, 2018
Japan Tiissue Engineeering Co., Lttd.
Nag
goya Universsity
Japan Tissu
ue Engineerin
ng Co., Ltd. (a Fujifilm GGroup compa
any; Presiden
nt: Ken-ichiroo Hata, “J-TEEC”, hereafteer)
annd Nagoya UUniversity (PPresident: Seeiichi Matsuoo) announcedd a three-pa
arty patent liccense agree
ement between
J-TEC, Nagoyya Universitty, and Shinshu Univeersity (Presiddent: Kunihiro Hamadaa) to develo
op a low-co
ost
manufacturing
g technology for genetica
ally modified autologous (*1) T cells (CAR-T(cellss) with enhanced targeting
fficiency aga
ainst cancer, as a theerapy for C
CD19*2-positive acute ly
ymphoblasticc leukemia (ALL)*3. Th
hiseffmanufacturing
g technologyy, jointly deve
eloped*4 by groups led by Professo
or Yoshiyuki Takahashi, Department ofPe
ediatrics, Naagoya Univerrsity and Pro
ofessor Yozo Nakazawa, Departmentt of Pediatriccs, Shinshu University,U
iss agrround-breakinng technolog
gy that is expected to ccontribute too the spreadd of CAR-T therapy which is drawing
atttention as a new cancer therapy.
Based on th
he agreemen
nt, J-TEC will acquire the exclusive rig
ghts to develop, manufaccture, and coommercialize inJa
apan the auto
ologous cell-derived theraapies targeti ng CD 19-poositive ALL us
sing this techhnology. Nag
goya Universsity
annd Shinshu U
University wiill receive ann upfront payyment upon signing of th
he agreemennt, as well asa payments atdeevelopment mmilestones and royalties from J-TEC based on saales.
CAR-T therrapy is an immmune cell therapy usin
ng CAR-T cells,cwhich area geneticaally modified T cells*5 withwennhanced targ
geting efficie
ency against cancer. Twoo therapies using autolo
ogous CAR-TT cells havee already beenap
pproved in th
he U.S. and havehbeen co
onfirmed to hhave high theerapeutic effiicacy.
It is commonn to use virall vectors*6 forr introducing CAR genes*7 into T cells
s collected froom the bloodd when making
CA
AR-T cells. However, th
here are iss
sues with th
his method, such as the high costt of viral veectors and thefacilities/equip
pment require
ed to contain viruses to eensure safetyy, leading to highh
manufaacturing costss.
The CAR-T cell manufaccturing technnology jointlyy developed by Nagoya UniversityU
annd Shinshu UniversityUdoesnoot use conve
entional viraal vectors when introduccing CAR genes, but innstead usess inexpensive
e vectors withwna
aturally-derivved enzymess. In addition, it does nott require spe
ecial facilities
s to contain tthe virus ins
side production
suuites and the need for qua
ality testing process
psuch
h as vector-dderived virus checks can also be avoiided. Thus, theneewly develop
ped manufactturing metho
od is expecte
ed to reduce manufacturin
ng costs for C
CAR-T cells..
J-TECJ
has manufacturring facilitiess that meett the standards*8 for manufacturin
mng and quality control ofregenerative m
medical prod
ducts. It deve
elops, manu
ufactures, and markets autologous
acuultured epide
ermis, Japann’s
first regenerattive medical product. Th
he company signed the three-party patent licennse agreemeent to grow its
pip
peline of reg
generative me
edical products. Tapping into its technology and knowhow
kon autologous cell culture, its
esstablished quuality assuran
nce system, and advanceed manufactturing facilitie
es, the compaany intends to promote thedeevelopment oof therapies using
uautolog
gous CAR-TT cells targeting CD 19-poositive ALL.
Nagoya Univversity began clinical ressearch on inntractable/rec
current CD 19-positive A
ALL with the support of theJapan Agency for Medical Research and Development (AMED)*9 in February 2018. It is one of Japan’s leading
medical facilities for the treatment and research and development of pediatric cancer. Utilizing the knowhow
cultivated in clinical practice, it will continue to promote further clinical applications.
Conventional従来の製造法
manufacturing method
ウイルス封じ込めのための特殊な施設・設備やSpecial facilities
required to contain virus insideproduction suites,ウイルスチェックが必要
virus checks also required.

T-cells

名大が信州大と共同で開発した製造法
New
manufacturing method

Facilities / equipment is not required to contain virus,

ウイルス封じ込めのための施設・設備、ウイルスチェックが不要で、no need for vector-derived virus checks. Can be

manufactured
at J-TEC existing facilities.
J-TECの既存施設・設備で製造が可能。

Special facility to handle viruses

Patient

introducing
CAR genes

T-cells

electricity

Patient

Virus vectors
T-cells

introducing
CAR genes

vectors
with naturally
天然由来の酵素ベクター-derived enzymes
T-cells

Virus checkCultureexpansion

Culture expansion“We had been exploring companies to partner with in clinical trials and commercialization after clinical researcheven before we began our clinical research in February 2018” said Professor Yoshiyuki Takahashi, Department ofPediatrics of Nagoya University, one of the inventors of the patented technology, “We chose J-TEC as our partner
for its track record in the development, manufacturing, and marketing of regenerative medical products, itsextensive knowhow on commercialization, and its well-equipped manufacturing and quality control facilities. Inaddition, Nagoya University and J-TEC are both based in Aichi Prefecture. We will work closely with J-TEC todeliver ground-breaking therapies to patients suffering from blood cancers as soon as possible.”“This CAR-T cell manufacturing technology developed jointly by Nagoya University and Shinshu University is
an extremely ground-breaking technology that does not use viruses.” said Ken-ichiro Hata, President of J-TEC.
“Efforts to identify clinical applications of therapies using this technology are underway at Nagoya University, which
is one of Japan’s leading sites for the treatment of pediatric cancer. It has a high affinity with our business as it alsouses the patient’s own cells. By combining with our resources, such as development knowhow on regenerative
medical products and our existing facilities, as well as the various technologies of the Fujifilm Group, we areconfident that we will be able to accelerate the commercialization of this technology. We will work to ensure theearly availability of therapies using high quality ‘autologous CAR-T cells’.”
Nagoya University will promote the development of ground-breaking therapeutic technologies including highquality cancer immunotherapy, contributing to the resolution of unmet medical needs.
J-TEC will accelerate the research and development of new regenerative medical products, contributing to theenhancement of the quality of life of patients through the commercialization and industrialization of regenerative
medicine.
* 1 Patient-derived cells.
* 2 A type of transmembrane protein expressed on the surface of cells. It is particularly expressed in the early stages of antibody-producing B cell
development.
* 3 A disease that develops when lymphocytes, a type of white blood cell, become malignant, and proliferate indefinitely. The disease does
develop in adults, but occurs relatively frequently in children age 6 and under. This agreement targets acute lymphoblastic leukemia with theexpression of CD 19 antigen.

* 4 Shared Nagoya University/Shinshu University Patent Application
Patent Application Number

PCT/JP2016/079989 (patent pending)

Name

Method of preparing genetically modified T cells with the expression of chimeric antigen receptors

ApplicantNagoya University, Shinshu University

Inventors

Nagoya University: Nobuhiro Nishio, Yoshiyuki Takahashi

Shinshu University: Yozo Nakazawa, Miyuki

Tanaka, Daisuke Morita
Fiscal 2015 Japan Agency for Medical Research and Development “Project for Commercialization of Innovative Research on Cancer
Therapeutics” “Development of chimeric antigen receptor T cell therapy using non-viral vectors for pediatric acute lymphoblastic leukemia”
commissioned research and development, patent application filed for the application of Article 19 of the Industrial Technology Enhancement
Act.
* 5 A type of lymphocyte. Includes killer T cells that kill cells infected by viruses or bacteria, and helper T cells that activate B cells to produce
antibodies and activate phagocytes that destroy pathogens, such as viruses. T cells have T cell receptors that bind specifically to certain
antigens, and this is how they express an immune response to that antigen.
* 6 Vectors are molecules that have the ability to introduce genes into cells. Viral vectors are vectors that use the nature of viruses to invade cellnuclei.
* 7 Genes that induce T cells to express chimeric antigen receptors (CAR). CARs are proteins created by artificially modifying T cell receptors,and they recognize specific antigens that are expressed on the surface of cancer cells and have the function of inducing/activating T cells.
* 8 Standards based on the “Law on Securing the Quality, Efficacy and Safety of Products including Pharmaceuticals and MedicalDevices”(Enacted November 2014).
* 9 Fiscal 2017 to 2019 Project for Commercialization of Innovative Research on Cancer Therapeutics. Subject: Commercialization of chimericantigen receptor T cell therapy using non-viral vectors for pediatric acute lymphoblastic leukemia.

For inquiries on information in this media release, contact:
Inquiries regarding the content of the agreement:
Japan Tissue Engineering Co., Ltd.
Corporate Planning Department, Corporate Management Division
TEL :+81-533-66-2020Inquiries regarding clinical research:
Nagoya University Hospital
TEL :+81-52-741-2111 (Operator)