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EKѧص㼰Ƶоչ

ʱ:2017-11-06 21:20Դ:δ֪ :yong :
EKռ40% ­ڳΣԼĶĿǰEKҪгΪۺơԭרŻȱϸҺ߷ӦʹEKϺͰƳΪܡEK

 EKռ40%­ڳΣԼĶĿǰEKҪгΪۺơԭרŻȱϸҺ߷ӦʹEKϺͰƳΪܡEKһֱȽǰƲԣҪƺƣзƷϸƷ߼ϼƵȷ

 

1.EKֵѧص

 

EKֳʽΧ֯ԽޣȫгEKֱȽѣ֮Ѫ-ԼҺ϶Իҩ赲ԼϸԷƵIJԣʶEKԤϲоΪEKֲܲĿ߷ӦEK΢ЧĿ߷ӦdzΪ΢дڵEKԴӣתβͱ谱ɫлȣʹTܰϸɥʧȻͨоԽԽ֤ݱEKֲдĿ߷Ӧֶͨ

 

ϵͳԶһȻһ߷ӦٶϸɾѪ-ԼҺϽϵͳáԼҺǡʡܰϵ֮һϵ۲񾭽ϸɱҪ֯Ըmajor histocompatibility complexMHCһЩϸر־ϵͳ΢Ŀԭϸ֯ϸȣEKϸһ߷ӦȱݣɲٴƿɴӴ˴֣ͨԤ;EKֽЧơٴEKƸһʷ½׶Ρ

 

2.EKֵ

 

2.1

 

ʹÿ塢Tϸܰӣɱϸܰϸƣ翹ƺ͹ϸơĿǰֱƵоɹѿʼӦٴ

 

2.1.1ڵƵãEKֳƷδȫϸԿΪƷϵͳ侫ܵϸӶƵİȫԡĿǰоķʹÿƬΣضЧӦϸͻ䡣źţӶ̼ϸ߷Ӧṩ̼źţԻϸ߰ԡ

 

EK֣ЩֳdzŷİȫԺЧEKֱ׼ṩһеĸԷͬλءϸҩ߶ؽϣơѽٴ׶ΣڻЧԣԶЧдо

 

2.1.2Tϸ͹ϸеãTϸһָϸЧCD4+TܰϸCD8+TܰϸNKTϸBܰϸͻ״ϸdendritic cellDCԼϸ/ϸϸķֻЧӦܣݵĹؼأԵTϸõĻоʹΪЧƵ°е㡣ϸƽϸϸ-ϸ̼ӣgranulocyte-macrophage colony stimulating factorGM-CSFע䵽˴Ƥ£Ӹɹܰͽռܰϸͨϸ濹ԭ-ACD3IL-2лռܰϸܾͨ䣬ӶﵽĿġ

 

PlautzȲùϸƷ12EK֣С42ֱ27º20ʱ޽չ̻ҪͨϸʵĿģȻɱϸnatural killerNKܰӼɱϸlymphokine-activated killer cellsLAKϸTܰϸcytotoxic T cellCTLȡ

 

Ŀǰϸתƣadoptive cell transferACTƾɫˣΪÿϻȡƱԴTϸȽѡ40%ԭԽĸϸɱƤͻ壨epidermal growth factor receptor variant EGFRv󣩣ԪϸѪƤϸ֯ṹнϸԣˣEGFRvΪһֽưе㣬ACTEKơ

 

2.2

 

ѴڻµĿ߷ӦͿԭݳϸơĿǰдٴǰо׶Ρ

 

2.2.1ԿΪƣͨǿ԰пԭߣǿ߷ӦѳɹֹһЩ˷硢Сԡ컨׺տȵȣ߼䴥ԭ¶ڵ߷ӦڽһоҪϸӻƷ棬ʹõ߷ͨϸTܰϸؿԭ-4cytotoxic T lymphocyte-associated antigen-4CTLA-41programmed death protein-1PD-1PD-1Դ壬鵼1ԴTϸͨ·Լʵ˹Ľڴ˻ϣĿǰһ¹۵㣺ƺҩEKֲ΢һЧܿ߷Ӧ

 

2.2.2ԿԭݳϸΪƣоҪڿԭݳϸӦáDCСϸʺ˹ϸǿԭݳϸɲ׽ԭͨMHCݳʸTϸ塣⣬ԭݳϸĹ̼B7TϸCD28ϣṩTϸһ̼źţTϸһͿ߷ӦֲԿӦϵͳĿǰ֪ĸֿԭݳϸУDCĿԭʹǿͨ񡢼ӹԭȻ󽫿ԭϢʸܰϸӶһϵ߷ӦĿǰжDCʵȡýϺÿЧ

 

СϸmicrogliasMGתΪDCǰϸGM-CSFڵ£תΪDCԴԿԿԭDCӦӦãֲ΢DCƾֲ״̬ӶǿϵͳĹܣýЧ

 

2.3Ʒradioimmuno therapyRIT

 

RITǰѵ¡ԭϵΪ壬żͬλؽϺעڣϸؿԭԽϣֲͬλر֯ߣӶ֯СһƷTenascincĿǰо϶ؿԭе㣬ÿTenascincĿ81C6I131EKֲˣܹڡ

 

2.4ϸƷ

 

ϸܹ̼ЧӦϸֳһ߹ܼΪ߻ԵЧӦϸܹ忹߹ܵЧӦΪҩѽжоγϸϸо㷺һ࣬ϸأIL-2IL-7IL-15IL-21IL-2תϸʾϸߵʣĿǰΩһFDA׼ӦõϸӡIL-7ӰTϸܹϵתΪϸЧӦTϸ

 

ٴǰоӦIL-7ƽ᳦С󣬿ӿ߽鵼ϸIFN-γıͬʱСEKģҲѾ֤IL-7ԤųⷴӦCD8+Tϸ鵼ٴо֤ӦIL-21ƺɫ˿ɻܻ22.5%12.4º޽չ4.3¡ȻϸƷܹյ㷺ЧӦ߷ӦǿҵĿЧӦҲϹ㷺ԡӦùϸתƺϸƷΪһָ

 

2.5߼ϼ

 

߼ϵͳдھõźͨ·ϸͨźͨ·ӱɱˡ߼ԿΪҪԭΪϸĿ壬Լֹ鵼ƵĿ塣PD-1CTLA-4Ŀǰо߼㡣һЩĸϸGBMУƻPTENȱʧB7ͬϵ1B7-H1߱ҲΪ壨PDL1GBMϸPDL1ʵʱвPDL1PD-1ܽϻᵼǰTϸԭԽԼTϸӦԽ͡ù֢̿ӦԼPDL1Ҳ΢еϸܰϸ

 

CTLA-4һֹ壬ҪTϸ;ֹTϸܹµTϸЧӦܺǿTϸƻԡ߼ڿѾȡnivolumabPD-1ƷOpdivoIpilimumabCTLA-4ƷYervoyںɫ˵ӦʾϺõٴЧ

 

3.չ

 

EK־ϮǿԳ̶ȸߵѧص㣬ơƵȴͳδȡЧΪһµƷٴǰģתٴĻо׶ΡĿǰѪ-ԼҺϵĴڣEKַƵĸԣ߻ԼҽѧƣEKƻһĻٴоֻΪۺֶεһ֣ܴŻƣͳƷƷϽΪǰEKƷ

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