® BCAS
Vol.34 No.3 2020
A New Patch for Improved CAR-T Cell Therapy
T
'dls are natural w a iiio rs to figlit against lu in o i, •ells in h u m a n b o d \. I he m a jo r rc c e p lo r •esponsihle for tu n io r anligen recognition in I
cells is the I cell receptor (T ('R ). I lowever. not all I ('11s recognize lum or aiui^ens.
Bv means o f g e n e tic e n g in e e rin g. I cells are (*c|ui|)))(4rl w ith c liin ie rii* a n tige n receptor (CAK) to s ije c ilic a lly recognize tu m o i- antigen and k ill tu m o r cells in human body. TAR-1 coll ihem py has acliie\ed
success in tre a tin g B c.dl iiu ili 巧
N o w. T A Ii-l cell th e ra j)\ is fa c in g m a jo r c lin ic a l c lia llr n 〇：es in rlu d iiig cvtokin e release s y n d io m r and poor persistence.
In a study published online in C e ll on July 29. a reseaivh team led bv Prof. \l (>henqi From ihe Center fo r E xce lle iu e in M olecular Cell Science. Shanghai Institute o f Biochem istry and (-ell Biology (SIBCB) of' tlie C'hinese Academy of Sciences. Prof. I ILANCx C'liaolan from Poking L ni\(M*sity I Iralth Science C^Miter. and l^rof. I I I ! I^nlu from L n ix e rs ity o f C a lifo rn ia. Sim l)i(*go. drvdoped a new stralc^v of CAR-1 n^ll tlim ip y based on new im derstandiniiof l ( li siiiiial transfluctioii.
I he researcliers liav(i lx k cn sludvini *： I cell biology fo r m ore than a decade. T h e ir earlier works unraveled new re g u la to iN in e c lia n is in s o f T C K a n d P D -l. and led to ihe d e \clo p m e n t o f new means o f cancer im m im otlieia|)y.
In th is stud y, bv iis in ^ im m u n o lo g ic a L mass spet'troinetiir. biochemical and l)iopliysic*{il techni(|iies. the reseaivlieis ir\e a lrd nrw sii>naling ioles (D 3e. a key signaling siihim it of 丨 CK.
I liev lound that (11)38 could re cru it m h ih ito ry signaling m 〇l(iru le (isk \ ia its m ono-phosphorylated
C ytokine release syndrom e
Poor cell persistance
Reduced cytokine production Enhanced cell persistance
Scientists developed a new strategy of CAR-T therapy by incorporating
the CD3e cytoplasm ic dom ain into the genetically engineered chimeric antigen receptor (CAR), and showed that this new 'molecular p a tc h 1 leads to re d u ce d cytokine productio n an d en h a n ce d persistence in mice. (Image by S IBC B)
□A M m o lif and could also rccniil slim ulatory molecuh* Pl.'^K via its B liS m otif. When (.l)3s was incorporated into the clin ica lly uscul 28Z CAR. K 28Z CAR-T evils had reduced cvtokin e p ro d iR tio n and (Mihanced cell poisistence. In the p ri'c lin ic a l anim al m o d ds. K 28Z CAR-1 ce lls sh o w e d b e tte r a n t i-tu m o r fu n c tio n compared to 2〇Z ( AJi-T cells.
At present, this study is bastnl on niouse models. I lie i csearchers w ill conlinue to explore its prom ising tra iis la lio n a l p o te n tia ls in (r ra lin g l)lood and solid maliii'iiaiuies.
(SIBCB)
Reference
buchiWei Wu, Qiuping Zhou, Takeya Masubuchi, Xiaoshan Shi, Hua L i, Xinyi Xu, Min Huang, L i Meng, Xing He, Hengyu Zhu, Shuaixin Gao, Nan
Zhang, Ruirui Jing, Jie Sun, Haopeng Wang, Enfu Hui, Catherine Chiulan Wong, Chenqi Xu, (2020) Multiple signaling roles o f CD3e and its application in CAR-T cell therapy. Cell 182, 855, doi: 10.ll.2020.07.018.
L i fe
Sciences
188
Bulletin of the Chinese Academy of Sciences
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