CAR-T技术,一种免疫治疗技术,一种或许能治愈癌症的技术,你或许听说过,或许没听说过,但它确实给我们带来了惊喜,给癌症病人带来了希望和期待。你肯定很想了解,什么是CAR-T技术?它的疗效如何?副反应又如何?它的出现是否真的预示着癌症将被彻底攻克?本文为你掰一掰。
一、什么是CAR-T免疫疗法?
我们的免疫系统在很多时候,都可以通过相应的细胞表面分子识别体内产生的异常细胞,并把它清除,但随着基因突变的产生,有些异常细胞的表面分子发生了变化,免疫系统不再把它当做敌人,无法把它清除,这时候,癌症就产生了。CAR-T(Chimeric Antigen Receptor T-Cell Immunotherapy),即嵌合抗原受体T细胞免疫疗法。CAR-T的治疗策略就是帮助免疫系统,主要是T淋巴细胞识别癌细胞,从而促使T细胞把癌细胞清除。科学家在研究中发现了癌细胞与正常细胞表达差异的一些分子,根据这些分子,设计一种名为CAR(嵌合抗原受体)的基因,这种CAR(嵌合抗原受体)可以和癌细胞表达的特异性分子结合。通过一种类似血液透析的方法,分选出病人体内的一些T细胞,然后在实验室将编码这种CAR(嵌合抗原受体)的基因导入,这样这些T细胞就能够表达这种新的受体。这些经过基因修饰的T细胞在实验室进行增殖,随后将它们输注回病人体内。这些T细胞利用它们表达的CAR(嵌合抗原受体)能够结合癌细胞表面上的分子,强效地激活这些T细胞,从而快速地摧毁癌细胞。
听着一头雾水吧?是不是很高大上?其实,说白了,它并不是一种药物,而是一种技术,确切地说是一种免疫疗法,而且是一种细胞疗法。一听细胞疗法,很多人马上会说,细胞疗法不是前几年那个魏则西事件被大家批判的东西吗?非也,此细胞疗法非彼细胞疗法,CAR-T免疫治疗本质上也是利用病人自身的免疫细胞来清除肿瘤细胞,但它是一种改良的新型细胞疗法。通俗一点说,就是把病人体内的T细胞(一种免疫细胞)拿出来,在体外进行一些改造(基因修饰,这个过程和原理普通老百姓弄不清楚也没关系),这可是关键操作,经过改造,就成了我们需要的CAR-T细胞,也就是嵌合抗原受体T细胞,它带有“导航系统”能够精准地找到并杀灭肿瘤细胞,这个威力就大增了,当然,一个或几个这样的细胞可不行,还得在体外进行扩增,说白了,就是多生一点子孙,然后将这些改造扩增后的“武器”回输到病人体内,癌细胞,你就等着颤抖吧,看我怎么收拾你!
CAR-T疗法的基本流程
二、CAR-T免疫疗法取得哪些“战绩”?
2014年CAR-T细胞技术获得美国FDA“突破性疗法”认证,被誉为“癌症治疗的第四次革命”。2017年7月12日,美国FDA肿瘤药物咨询委员会(Oncologic Drugs Advisory Committee,ODAC)以10:0的投票结果一致推荐批准诺华公司的CAR-T疗法CTL019的生物制剂许可申请(BLA),用于治疗患有晚期白血病的儿童和年轻成人患者。8月31日,FDA正式批准诺华突破性CAR-T疗法 Kymriah上市。从1989年,美国科学院院刊(PNAS)报道了第一代CAR-T疗法,现在CAR-T已经发展到了第四代。CAR-T在治疗白血病中取得了长足的进展。
很多研究表明,对于难治复发性白血病,缓解率在70%-80%左右,个别小样本甚至达到了100%。其中急性淋巴细胞白血病的治疗效果尤为突出。同时,也有大量的小样本试验表明,CAR-T在淋巴瘤、多发性骨髓瘤等血液系统肿瘤,均取得了可喜的结果。最近国际多个杂志分别发表了关于CAR-T的最新研究,NEJM报道了一例关于脑胶质瘤转移到脊髓,使用CAR-T治疗获得了有效缓解,肿瘤大部分消失的病例。Science子刊报道了晚期淋巴瘤病人经CAR-T细胞免疫疗法治疗后病情完全缓解的研究,OncoImmunology报道了体外对肺癌细胞系进行杀伤实验获得成功等等一系列的关于实体肿瘤的研究进展。还有更多的研究正在进行,很多研究都显示出了CAR-T令人欣喜的结果。目前有很多关于CAR-T技术治疗癌症(除了白血病,还有淋巴瘤,还有实体肿瘤)的临床试验在进行中,期待带给我们新的惊喜。
三、CAR-T免疫疗法是否“完美无缺”?
尽管CAR-T疗法取得诸如“战绩”,而且“战果”(适应症)似乎仍在扩大之中,但必须承认,CAR-T疗法也面临着很多挑战。随着研究的深入,临床样本的增加,越来越多的研究发现了CAR-T存在的副作用。主要包括以下几个方面:细胞因子风暴、神经毒性和B细胞发育不全。对于副反应的防治,虽然已经取得一些进展,但还需要进一步探索。
除了副反应,使用CAR-T治疗后的远期疗效,也存在很大的考验。在CAR-T治疗效果最为明显的白血病领域,复发率也非常高。多个研究表明对于急性淋巴细胞白血病,虽然临床缓解率可达80%以上,但是1年内的复发率也可达到40%以上。这可能与改造的T细胞无法长期存在于体内,以及存在由于癌细胞表达的多种免疫逃逸因子,引起T细胞衰老效应有关,具体还有待进一步探索。虽然在部分的实体瘤相关临床研究中看到了星星之火,但是,众多的研究表明,基于实体瘤血管紊乱,部分瘤体中心血运差,T细胞无法进入,以及细胞表面靶向分子标记有限等等困难,CAR-T在实体瘤中的应用还需进一步探索。
四、CAR-T免疫疗法是否预示着癌症将被彻底攻克?
结论来了!综上以上分析,在长时间和癌症抗争的过程中,CAR-T免疫治疗如一缕清风,让我们在攻克癌症的道理上看到了新的希望,也让我们有理由不断去期待。但也不得不承认,现在就下结论说CAR-T免疫疗法预示着癌症将被彻底攻克,为时尚早。革命尚未成功,同志还须努力。
部分主要参考文献:
1. Bridget M. Kuehn. The Promise and Challenges of CAR-T Gene Therapy. JAMA. Published online November 22, 2017. 2017.15605
2. Pettitt D, Arshad Z, Smith J, et al. CAR-T: A Systematic Review and Mixed-Methods Analysis of the Clinical Trial Landscape[J]. Molecular Therapy, 2017.
3. Brown C E, Alizadeh D, Starr R, et al. Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy[J]. New England Journal of Medicine, 2016, 375(26):2561.
4. Wei X, Lai Y, Li J, et al. PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells.[J]. Oncoimmunology, 2017, 6(3):-.
5. Turtle C J, Hanafi L, Berger C, et al. Immunotherapy of non-Hodgkin lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells[J]. Science Translational Medicine, 2016, 8(355):355ra116
misoprostol online order – buy misoprostol 200mcg online buy diltiazem pill
purchase cenforce generic – glucophage 500mg price buy metformin 1000mg sale
cialis 40mg pill – order viagra 50mg online sildenafil 20mg
Hurrah! Finally I got a website from where I know how to actually obtain helpful data concerning my study and knowledge.
Your style is really unique in comparison to other folks I have read stuff from. Thanks for posting when you have the opportunity, Guess I will just bookmark this page.
vuaxetai.vn
Appreciate it! A good amount of knowledge!
online.casino real money https://casinoslotssaid.com/live-blackjack-casino/ dinosaurio casino online
purchase semaglutide generic – order semaglutide for sale generic cyproheptadine 4mg
гѓ—гѓ¬гѓ‰гѓ‹гѓійЂљиІ©гЃЉгЃ™гЃ™г‚Ѓ – г‚ёг‚№гѓгѓћгѓѓг‚Ї еЂ‹дєєијёе…Ґ гЃЉгЃ™гЃ™г‚Ѓ г‚ёг‚№гѓгѓћгѓѓг‚Ї е‰ЇдЅњз”Ё
Good postings. Many thanks!
casino saint tropez online top online real money casino canada beste online casino app
Whoa many of useful info.
top paying online casino nz 2021 casino online slots free online casino florida real money
Wow all kinds of valuable information!
888 casinos online casino online slots hollywood online casino wv
Kudos, Good information!
american casino episodes online gambling casino online game king online casino
Fantastic forum posts. With thanks.
online casino min deposit 5 online casino canada best online casino slots real money usa
You revealed that perfectly.
casino and slots online free online casino real money bellagio online casino real money
Nicely put. Many thanks.
borgata online casino customer support free online casino stargames online casino echtgeld
cheap augmentin – augmentin 625mg without prescription purchase levothyroxine pill
cleocin 150mg without prescription – order cleocin 150mg without prescription brand indomethacin
Awesome postings. Thanks a lot!
ugandan online casino casinos online casino city center online
You reported it really well!
new online casinos australia no deposit bonus real casino online for real money como jugar casino online y ganar dinero
You said it nicely..
online casino immersive roulette casino rewards canada va casino online
Amazing loads of helpful info!
best online gambling casino online casino slot games call and surf online casino
Thanks. An abundance of info!
philly live casino online us online casinos free online casino no download
You actually expressed that very well!
online casino 247 register casino online games real money aaa online casino
You made the point!
bedste online casino bonus brand new online casinos usa no deposit bonus codes top legit online casinos
Thanks! A good amount of info.
888 online casino australia quick hit casino online slots sign up bonus casino online
Excellent stuff. Many thanks.
james bond casino royale online stream online casino sign up bonus free casino games online slots
Thanks a lot. Lots of tips!
italy casino online casino online slots free casino ideal online
Awesome facts. Thanks a lot!
casino keno online best casinos online canada nj casino online
You actually explained it exceptionally well.
online casino roobet online usa casinos illinois online casino real money
Amazing posts. Cheers!
snai casino online play casino slots for free online how to get money from online casino
Really a lot of wonderful facts!
biggest online casino welcome bonus’ top 10 online casinos usa online casinos free play
Wow loads of great data!
filme online casino royale online casino slots real money best canadian casinos online
“I thought you usually showered after practice. In the locker room.” His dad asks as he walks into the open door of the bathroom.
Incredible a lot of great facts.
online casino real money south carolina new usa online casinos real money fortune coin online casino
“You know what you have to do. Doncha. Son.” His dad says. Exactly a week after, daddy texted me with a different tone saying, “ get your ass ready tonight cause daddy is coming to your place tonight.” He was usually really sweet and nice, I was shot when I got the message. But automatically I said, “ yes daddy!” I guess I am a slutty whore for him right at the beginning as I knew my place where is always going to be inferior.
prednisone 10mg price – zovirax oral buy permethrin cheap
how to buy permethrin – order tretinoin gel without prescription buy generic retin for sale
His father kicks the shoes from his feet and slides his khaki pants off, while still holding, the resistant nut-sac of his virile son in his right hand. He is now as naked as his 17-year-old son. free porn sex “What did Coach have to say when he saw all those hard-young cocks in the locker room?” His dad asks.
You actually revealed it wonderfully!
instant withdrawal casinos online online casino reviews new online casinos australia 2018
Incredible lots of amazing advice.
orion stars online casino download free online games casino america online casinos
You actually reported that exceptionally well!
no deposit online casino instant payouts online us casinos a9play official online casino
Good data. Regards.
what online casinos have no deposit bonus codes best online casino usa best online casino jamaica
Amazing info. Cheers!
online casino reviews 1 site for best online casinos online gaming casino best arab online casino
accutane 20mg for sale – accutane online order deltasone drug
Regards! I appreciate it!
hippodrome casino online sign in new online casino no deposit bonus usa game vault online casino
Nicely put. Thanks.
low deposit online casino australia online casino welcome bonus bally’s nj online casino promo code
You stated it perfectly.
online casino strategy reddit casino live online atm online online casinos
Appreciate it. Quite a lot of postings.
spela online casino utomlands best online casinos that payout usa online casino jack
Regards! Awesome information.
new online casinos in the usa new usa online casinos with no deposit bonuses beste curacao online casino 2022 – sofort auszahlungen
You said it very well.!
nj real money online casino online casino for real money usa excalibur casino online
Fantastic knowledge. Thanks.
can you win at online casinos top online casinos winner online casino login
Whoa tons of superb facts.
stream casino online online casino for real money usa online casino spiele beste auszahlung
You actually stated this effectively!
pa online casino promo codes for existing users casino online games juwa casino online 777 guia
Thank you, I appreciate it!
online casino franГ§ais usa casino online online casino roulette trick
Many thanks, A lot of information!
tips for online casino online betting casino online casino 100 deposit bonus
Nicely put. Many thanks!
online casino dragonfish online gaming casino bandar betting sbobet casino online
Whoa plenty of fantastic facts.
az legal online casino online casinos for united states online casino facts
Regards. Ample tips.
best casino in ontario online casinos online starlight online casino
You have made the point!
online casino big bass bonanza online casino sites stargames online casino login
You mentioned that well.
live casino games online malaysia online casino bonus no 11clubs casino online malaysia
You said it adequately.!
king kong 777 online casino login online casinos with no deposit bonus admiral casino online review
Thanks a lot, I like it!
mauritian online casinos online casinos with no deposit bonus best core gaming online casino sites
Incredible many of excellent knowledge!
royal 888 casino register online best online casino mentor juwa 777 apk online casino v1 0.53 download
Lovely facts. Appreciate it.
best online us casino best online casino welcome bonus no deposit bet us online casino
Thanks, Plenty of information.
how does an online casino work new online casino usa agent online casino malaysia
You made your point.
casinos bonos bienvenida gratis sin depГіsito en mГ©xico online online casino top rated online casino golden tiger
Many thanks, Excellent stuff!
casino online free slots casino online play free legit casino online games
Terrific data, Thanks.
online casino mit paysafecard bonus [url=https://uscasinoguides.com/#]monkeytilt best online casino[/url] panda master online casino login
Fantastic postings. Appreciate it.
owning online casino online casino free spins no deposit online casino cherry
You explained it very well.
mystake casino online online casino bonus codes american online casino accepts british players
Awesome advice. Thanks a lot.
free real online casino best casino online dash online casino
Nicely put. Thanks a lot.
australian online casino paypal online casino free play online casinos accept paypal
Nicely put, Kudos.
red rock casino online us online casinos steak online casino
Thanks a lot. Quite a lot of forum posts!
ut online casino sites new casino online casino online no account
Incredible loads of useful information.
ny online casino apps casino online big daddy casino online login
baclofen 10mg sale – order lioresal online cheap buy piroxicam 20 mg generic
Nicely put, Thanks a lot!
casino online bonus gratis senza deposito https://usagamblinghub.com/live-casinos/ online casino isle of man
buy generic pyridostigmine – buy sumatriptan paypal oral azathioprine 25mg
diclofenac for sale online – order imdur 20mg pill cheap nimodipine generic
Amazing tons of amazing facts.
https://usagamblinghub.com/legit-casinos/
Awesome write ups. Thank you.
https://uscasinoguides.com/shazam-review/
oral cambia – aspirin 75 mg brand generic aspirin 75mg
generic calcort – order brimonidine online alphagan cheap
besifloxacin order online – besifloxacin cheap buy cheap sildamax
ygcxse
lactulose brand – betahistine 16mg ca order betahistine generic
speman cost – order himplasia without prescription finasteride where to buy
buy finax for sale – buy uroxatral 10mg generic uroxatral medication
lasuna pill – buy diarex generic himcolin order
order generic atorvastatin – order nebivolol 20mg how to buy bystolic
brand tenormin 100mg – purchase carvedilol pill buy generic carvedilol online
rogaine where to buy – order proscar 1mg pills propecia drug
durex gel order online – buy durex gel for sale buy zovirax without prescription
ascorbic acid ca – brand isosorbide dinitrate cheap compro tablets
zofran 4mg drug – order procyclidine sale requip 1mg for sale
order cyclobenzaprine 15mg generic – olanzapine 10mg tablet buy vasotec 5mg generic
order aldactone 25mg pill – where to buy prothiaden without a prescription order naltrexone 50 mg sale
buy norpace online – cost pregabalin 150mg purchase chlorpromazine generic
order divalproex for sale – purchase aggrenox without prescription order generic topamax 100mg
hydrea tablet – crixivan pill robaxin 500mg tablet
piracetam oral – secnidazole brand brand sinemet 20mg
buy feldene 20mg pills – order exelon 3mg generic rivastigmine 3mg canada
monograph 600 mg ca – order etodolac 600mg online cheap pletal medication
cost dimenhydrinate 50mg – dramamine price brand risedronate 35 mg
forxiga 10mg tablet – sinequan 75mg pill precose generic
buy griseofulvin without prescription – fulvicin price buy generic lopid over the counter
order cotrimoxazole 960mg sale – tobra sale buy tobramycin cheap
dulcolax 5 mg drug – oxybutynin 5mg pills buy generic liv52
buy aciphex without a prescription – domperidone 10mg without prescription domperidone oral
fludrocortisone pills crawl – nexium pills continue lansoprazole pills sherlock
biaxin pills nearby – biaxin pills calm cytotec pills dread
promethazine duchess – promethazine read promethazine crack
ascorbic acid four – ascorbic acid tone ascorbic acid velvet
dapoxetine consult – priligy flag dapoxetine rack
valtrex online barrel – valacyclovir pills color valacyclovir online local
claritin pills last – loratadine trick claritin lash
pills for treat prostatitis trade – prostatitis medications gigantic prostatitis treatment grim
uti antibiotics dollar – uti antibiotics uncertain treatment for uti may
asthma treatment stab – asthma treatment immediate inhalers for asthma material
acne treatment alone – acne medication niece acne medication pleasant
cenforce sideway – tadalafil generic brand viagra bond
cialis soft tabs weak – cialis super active maintain1 viagra oral jelly online print
cenforce online thou – zenegra pills favourite brand viagra online year
dapoxetine cap – dapoxetine control cialis with dapoxetine labour
buy viagra professional world – malegra another levitra oral jelly online steady
crestor online keeper – caduet online somewhat caduet difficult
how to buy nitroglycerin – buy lozol medication purchase diovan online
order hydrochlorothiazide 25mg generic – buy lisinopril 5mg generic zebeta 5mg price
purchase metoprolol sale – benicar online order buy generic adalat 10mg
digoxin 250mg ca – furosemide 40mg over the counter lasix sale
order famvir 250mg generic – valcivir buy online order valcivir 500mg generic
purchase nizoral pills – order nizoral online order itraconazole generic
yGlLkReFzCVgIi
buy semaglutide 14 mg generic – rybelsus 14 mg us desmopressin canada
terbinafine 250mg for sale – where to buy lamisil without a prescription grifulvin v online order
buy generic micronase 2.5mg – order generic micronase 2.5mg buy dapagliflozin sale
buy desloratadine 5mg – aristocort 4mg brand purchase albuterol sale
methylprednisolone sale – buy montelukast paypal brand azelastine 10 ml
purchase ventolin inhalator generic – order albuterol inhalator online cheap buy theo-24 Cr without a prescription
ivermectin 6 mg for people – eryc 500mg without prescription buy cefaclor 500mg without prescription
cost cleocin 150mg – buy cefpodoxime 100mg pills buy chloromycetin sale
order zithromax generic – order ciplox generic ciprofloxacin 500 mg without prescription
amoxicillin cost – purchase amoxil oral cipro
buy augmentin 1000mg sale – buy myambutol 1000mg generic brand cipro 500mg
buy hydroxyzine online – hydroxyzine 10mg cost endep pills
anafranil cheap – order remeron 30mg online cheap buy generic doxepin
seroquel over the counter – cheap eskalith generic order eskalith pill
clozaril buy online – order aceon 8mg online cheap buy generic famotidine 20mg
purchase zidovudine for sale – how to get glycomet without a prescription buy allopurinol online
KoLVlgFUZeAr
order generic glycomet 1000mg – order lincomycin 500mg for sale buy lincocin medication
order furosemide for sale – coumadin sale purchase capoten online
buy cheap ampicillin order penicillin generic order amoxil for sale
metronidazole 200mg ca – buy generic oxytetracycline over the counter zithromax 250mg drug
valtrex 1000mg canada – purchase nemasole generic brand acyclovir
stromectol 3 mg tablets price – tetracycline 250mg usa order tetracycline
metronidazole 200mg canada – amoxil sale azithromycin sale
buy ciplox sale – order amoxicillin pills
erythromycin 250mg sale
baycip uk – septra pill augmentin ca
baycip sale – bactrim 480mg price augmentin 375mg sale
buy lipitor generic cheap lipitor atorvastatin 20mg uk