UG

AAV
AAVƱ
688238
زƱ
688238
English
UG(й)ٷվ
˾˶

Nat Commun | ˣTϸɱTϸѾ

ʱ䣺2022-08-17 ȶȣ


ǰ


20227£ϺͨѧѡŶNature Communications“T cell receptor β-chain-targeting chimeric antigen receptor T cells against T cell malignancies”оʹTϸTϸ壨T cell receptor, TCRβɱԣƺ͹ǶϿԭ壨chimeric antigen receptor, CARͨһϵʵ֤ʵһCAR-TϸսԵ徲Ժ

 


Tϸֻڻ»ʽϸߣ໼ȻḴTϸƴشСӰҪԿٴµսCAR-TϸBϸȪԴİѪʾЧTϸȻCAR-TϸƱлϸԼCAR-TϸɱˣɱTϸΪֹЩ⣬ҪѡϸĿԭ

 

TϸУTCRȪԴαβɱ--ṹvariable-diversity-joining-domain, VDJ-domainĻTCR βɱı52VβƬϣ1DƬϺ13JƬϣͬʱVβƬ24壬ÿTϸ¡ѡ1ƬϾϣˣTCRеضTCR Vβ͵ķƵԼĪ0.58-10.84%ΪTϸTϸ¡Ϊ򵥣ֻͨ1ضTCR VβVαʹһϸTϸӦCAR-Tϸ

 

о˼
 

01  ضVβCAR-TϸCAR-TϸеͨTϸԼVβ8-Vβ8+ϸϵVβ8-CAR-Tϸɱ˱


02  ںһԭ̼¼Vβ8-CAR-Tϸֳάֺɱ


03  ȱСģ֤Vβ8-CAR-TϸĿЧ


04  ԰Vβ5CAR-Tϸɱ˱;ظ֤ؿսùģ


05  ضVβTϸȱʧ˳ӦߵӰ죬֤CAR-Tս徲


о
 

 ȣʹܹʶTCR βɱVṹVβ8, Vβ5, Vβ13Ŀ壬䰱кӦĵɱƬϣsingle-chain variable fragment, scFv4-1BBCD3ζϹCARüԭTϸƱVβ͵CAR-TϸЩCAR-TϸּضVβʣЩCAR-Tϸȷʵ԰VβԵTϸTαβûӰVβ8CAR-TϸTϸVβ8+ TϸȺ½ϸصϸIFN-γTNF-α͸

UG(й)ٷվ
 

ʹ293ϸJurkatϸֹԵVβ8-Vβ8+ϸTϸVβ8-CAR-TϸֻеVβ8+ϸVβ8-CAR-TϸʱŻ⵽TϸIFN-γTNF-αͷţԼgranzyme BıVβ8+ JurkatϸŻɱˣҼcaspase-3ˮƽעϸ

 

 

Ϊ˼CAR-Tϸֳϸɱʹ÷յVβ8+ RajiϸΪԭһظ̼Vβ8-CAR-TϸͨȪԴCAR-Tϸ߷ظĿԭ̼ܹһֱVβ8-CAR-TϸĿΪTϸˢ£ҲûзCD3CD5CAR-Tϸ໥ɱ˵ϸԼʵעTϸȣ̼׶εVβ8-CAR-TϸVβ8+ Jurkatϸɱ

 

 

߽һ֤Vβ8-CAR-TϸĿЧȱݵNSGСJurkatϸֲģӣעTϸVβ8-CAR-TϸЧעVβ8-CAR-TϸƵСʽѪƢ͹еϸĿŽͣʾʱ̭

 

 

ʹVβ8е֤ʵVβսú߲֪ڴˣϣùģչTܰϸΪˣ߹Vβ5-CAR-TϸԼVβ5ԵϸCCRF-CEMHut-78 TϸϵVβ8ʵЧһ£Vβ5-CAR-TϸƱУVβ5Tϸɨ⹲ʵУVβ5-CAR-TϸܹɱVβ5+CCRF-CEMHut-78 TϸҽVβ5+ϸʱ͸IFNγͬʵУVβ5-CAR-TϸעܹVβ5+CCRF-CEMֲɣС

 

 

VβսȻʾϺõĿЧԱһΣCAR-TϸṥVβ͵Tϸ߽һս徲ԾijضVβ͵TϸռTϸһС֣ƲڰTϸCD5CD7CD3CAR-TսԣһСTϸȱʧᱬصΪ֤һϣ߽ѡȥVβ8+ TϸСģVβ8ԿļעСVβ8+ TϸԼռTϸ21.5%ʹͬscFvƬƱVβ8鿹壬ģVβ8+ TϸȱʧCD3ε崦óͷСΪԱ

 

߶ԸСģעDEC-OVA磬Vβ8崦óͷС󱬷DEC-OVAˮƽԼOT-ITϸӦˮƽҰСƣCD3ε崦óͷС󱬷DEC-OVA̭OT-ITϸӦȫ߽һԽB16-OVAϸСп߼⣬Vβ8+ TϸȱʧСҰСһ£CD3ε崦óͷTϸȱʧСԽѸVβ8+ TϸȱʧСϸҺ߷ӦЩӰ

 

 

 ʹTCR βɱضΪе㣬ԵCAR-Tϸսԣ֤ʵսܹɱض͵Tϸͬʱֵ˳Ӧ߹Чٴһָ

UGջۣڻIJЧͺ͹˾еϸƽ̨ǿΪṩװϸ깹ʽѡСֲģӹͰڵֶЧͣΪṩ漰Ķо֧ 
һ һ
?ɨ뷴

ɨһɨĿҳ

ѯ
ɨע

UG

ض
վͼ