{"id":9925,"date":"2021-02-17T17:33:40","date_gmt":"2021-02-17T14:33:40","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=9925"},"modified":"2021-02-17T18:01:53","modified_gmt":"2021-02-17T15:01:53","slug":"car-t-hucre-tedavisi-bugun-ve-yarin","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/car-t-hucre-tedavisi-bugun-ve-yarin\/","title":{"rendered":"CAR-T H\u00fccre Tedavisi: Bug\u00fcn ve Yar\u0131n"},"content":{"rendered":"\n<p>V\u00fccudumuzu her t\u00fcrl\u00fc \u201cyabanc\u0131\u201d n\u0131n zararl\u0131 etkilerinden korumak \u00fczere tasarlanm\u0131\u015f olan imm\u00fcn sistemimiz, kanser oda\u011f\u0131 geli\u015ftirmeye yatk\u0131n olan h\u00fccreleri ortadan kald\u0131rma kabiliyetine de sahiptir. Her birimizin v\u00fccudunda her daim bu sava\u015f s\u00fcrmekte ve \u00e7o\u011fu zaman imm\u00fcn sistem meydandan galip ayr\u0131lmaktad\u0131r. Fakat imm\u00fcn sistem ne yaz\u0131k ki nama\u011flup unvan\u0131n\u0131 baz\u0131 durumlarda kaybeder ve hepimizin yak\u0131ndan bildi\u011fi kanser h\u00fccreleri h\u0131zla \u00e7o\u011falmaya ba\u015flar. Bu h\u00fccreler, imm\u00fcn sistemi yan\u0131ltmak i\u00e7in \u00e7e\u015fitli proteinler eksprese ederler ve kendilerini bir dost gibi g\u00f6stermekte ustalard\u0131r. Ara\u015ft\u0131rmac\u0131lar, y\u0131llar i\u00e7inde imm\u00fcn sistemi kanser h\u00fccrelerine kar\u015f\u0131 daha sald\u0131rgan hale getirmenin yollar\u0131n\u0131 aram\u0131\u015flar ve imm\u00fcnoterapi konseptini ortaya \u00e7\u0131karm\u0131\u015flard\u0131r. G\u00fcn\u00fcm\u00fczde imm\u00fcnoterapi ba\u015fl\u0131\u011f\u0131 alt\u0131nda bir\u00e7ok tedavi t\u00fcr\u00fc bulunmakta olup, bu yaz\u0131mda \u00f6zel olarak de\u011finmek istedi\u011fim CAR-T (Kimerik Antijen Resept\u00f6r- T) h\u00fccre tedavileri bu tedavilerin en yenilerinden bir tanesidir.<\/p>\n\n\n\n<h3>CAR-T H\u00fccre Tedavisi Nedir?<\/h3>\n\n\n\n<p>Bu tedavinin temelinde t\u00fcm\u00f6r h\u00fccreleri \u00fczerindeki proteinleri tan\u0131yabilecek T-h\u00fccresi resept\u00f6rleri tasarlayarak kanser h\u00fccrelerini ortadan kald\u0131rma amac\u0131 yatar. CAR-T h\u00fccrelerinin elde edilme a\u015famalar\u0131 \u015fu \u015fekildedir:<\/p>\n\n\n\n<p>\u00d6ncelikle hastan\u0131n kan\u0131 al\u0131n\u0131r ve T h\u00fccreleri ayr\u0131\u015ft\u0131r\u0131l\u0131r.&nbsp; Ard\u0131ndan bu h\u00fccreler vir\u00fcsler veya genetik m\u00fchendisli\u011fi y\u00f6ntemleri yard\u0131m\u0131yla istenilen kimerik resept\u00f6rleri ta\u015f\u0131yacak hale getirilirler ve laboratuvar ortam\u0131nda \u00e7o\u011falt\u0131l\u0131rlar. \u015eu an en \u00e7ok kullan\u0131lan yakla\u015f\u0131m CD19 ad\u0131 verilen h\u00fccre y\u00fczeyi proteinine ba\u011flanma yetene\u011fi olan resept\u00f6rler \u00fcretmektir. Sonras\u0131nda h\u00fccreler hastaya geri enjekte edilerek bu h\u00fccrelerin hastan\u0131n v\u00fccudunda da \u00e7o\u011falmalar\u0131 ve kanser h\u00fccrelerine kar\u015f\u0131 etkili olmalar\u0131 beklenir. Bu tedavi daha \u00e7ok kan kanserlerine y\u00f6nelik kullan\u0131mda olup 2017\u2019de FDA onay\u0131n\u0131 alm\u0131\u015f olan 2 ila\u00e7 piyasada bulunmaktad\u0131r.<\/p>\n\n\n\n<figure class=\"wp-block-image\"><img src=\"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/e\/e2\/CAR_T-Cell_Therapy.jpg\/453px-CAR_T-Cell_Therapy.jpg\" alt=\"File:CAR T-Cell Therapy.jpg\" \/><figcaption><a href=\"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/e\/e2\/CAR_T-Cell_Therapy.jpg\/679px-CAR_T-Cell_Therapy.jpg\" data-type=\"URL\" data-id=\"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/e\/e2\/CAR_T-Cell_Therapy.jpg\/679px-CAR_T-Cell_Therapy.jpg\">https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/e\/e2\/CAR_T-Cell_Therapy.jpg\/679px-CAR_T-Cell_Therapy.jpg<\/a><\/figcaption><\/figure>\n\n\n\n<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<iframe loading=\"lazy\" title=\"CAR T-Cell Therapy: How Does It Work?\" width=\"800\" height=\"450\" src=\"https:\/\/www.youtube.com\/embed\/OadAW99s4Ik?feature=oembed\" frameborder=\"0\" allow=\"accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture\" allowfullscreen><\/iframe>\n<\/div><\/figure>\n\n\n\n<p><\/p>\n\n\n\n<h4>Olas\u0131 Yan Etkiler Nelerdir?<\/h4>\n\n\n\n<ul><li>Covid-19\u2019da da ad\u0131n\u0131 s\u0131kl\u0131kla duydu\u011fumuz Sitokin Sal\u0131n\u0131m Sendromu ortaya \u00e7\u0131kabilmektedir.<\/li><li>Yukar\u0131da da bahsedildi\u011fi \u00fczere CD19\u2019a ba\u011flanan resept\u00f6rler \u00fcretilmektedir ve CD19 v\u00fccudumuzun sa\u011fl\u0131kl\u0131 B h\u00fccrelerinde de bulunmaktad\u0131r. Bunun bir sonucu olarak hastalarda B-H\u00fccre Aplazisi g\u00f6r\u00fclebilmekte ve bir s\u00fcre \u0130mm\u00fcnoglobulin tedavisi almalar\u0131 gerekebilmektedir.<\/li><li>Serebral \u00d6dem nadir de olsa g\u00f6r\u00fclen bir yan etki olarak bir klinik denemede not edilmi\u015ftir.<\/li><li>Bir\u00e7ok hastada g\u00f6r\u00fclen fakat k\u0131sa s\u00fcrede ortadan kaybolan konf\u00fczyon, n\u00f6bet gibi N\u00f6rotoksisite belirtileri g\u00f6r\u00fclebilmektedir.<\/li><\/ul>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p>CAR-T h\u00fccrelerinin \u00fcretim \u015fekli, her hastan\u0131n kendi kan\u0131ndan T h\u00fccrelerinin elde edilmesi prensibine dayal\u0131 oldu\u011fundan olduk\u00e7a zahmetli ve masrafl\u0131 bir y\u00f6ntemdir. Bu da bu tedavinin yayg\u0131n olarak kullan\u0131ma girmesi \u00f6n\u00fcndeki en b\u00fcy\u00fck engellerden biri olarak kar\u015f\u0131m\u0131za \u00e7\u0131kmaktad\u0131r.&nbsp; Ara\u015ft\u0131rmac\u0131lar yan etkisi d\u00fc\u015f\u00fck ve uygun maliyetli alternatif aray\u0131\u015f\u0131nda \u015fimdiden yol kat etmi\u015f durumdad\u0131rlar. Bilim camias\u0131nda son d\u00f6nemlerde s\u0131kl\u0131kla konu\u015fulan alternatif tedaviler \u015funlard\u0131r:<\/p>\n\n\n\n<p><\/p>\n\n\n\n<h3>CAR-T H\u00fccre Tedavisinin Allojenik Uygulanmas\u0131<\/h3>\n\n\n\n<p>FDA onayl\u0131 olan tedaviler hastan\u0131n kendi h\u00fccrelerinin modifiye edilmesiyle olu\u015fturulmakta ve bu hem olduk\u00e7a masrafl\u0131 bir s\u00fcre\u00e7 olu\u015fturmakta hem de yakla\u015f\u0131k 3 hafta gibi bir bekleme s\u00fcresine sebebiyet vermektedir. Ayr\u0131ca baz\u0131 kan kanserlerinde zaten T h\u00fccresi fonksiyonlar\u0131nda bozulma oldu\u011fu ger\u00e7e\u011fi g\u00f6z \u00f6n\u00fcnde bulunduruldu\u011funda otolog tedavi baz\u0131 hastalar i\u00e7in bir se\u00e7enek olman\u0131n d\u0131\u015f\u0131ndad\u0131r. T h\u00fccrelerinin allojenik olarak toplanarak kimerik resept\u00f6rlerin olu\u015fturulmas\u0131 ve bu h\u00fccrelerin her daim kullan\u0131lmaya haz\u0131r formda depolanmas\u0131 bu problemlere \u00e7\u00f6z\u00fcm olabilecek bir alternatif olu\u015ftursa da allojenik tedavinin de baz\u0131 kendine \u00f6zg\u00fc riskleri bulunmaktad\u0131r. \u00d6rne\u011fin; ba\u015fka bir bireye ait T h\u00fccreleri enjekte edildi\u011finden hastan\u0131n ba\u011f\u0131\u015f\u0131kl\u0131k sistemi taraf\u0131ndan bu h\u00fccrelerin h\u0131zla yok edilmesi ihtimal dahilindedir. Ayr\u0131ca enjekte edilen T h\u00fccrelerinin de al\u0131c\u0131n\u0131n ba\u011f\u0131\u015f\u0131kl\u0131k sistemine sald\u0131rarak GvHD (Graft Versus Host Disease)\u2019e sebep olma olas\u0131l\u0131\u011f\u0131 bulunmaktad\u0131r. CAR-T h\u00fccrelerinin \u00f6mr\u00fcn\u00fc uzatabilmek i\u00e7in CD52&#8217;nin h\u00fccre y\u00fczeyinden \u00e7\u0131kar\u0131lmas\u0131 gibi genetik m\u00fcdahalelerde bulunularak tedavinin efektifli\u011fi artt\u0131r\u0131lmaya \u00e7al\u0131\u015f\u0131lmaktad\u0131r.<\/p>\n\n\n\n<p>\u0391\u03b2 resept\u00f6rl\u00fc T h\u00fccrelerinin GvHD patogenezinde ve transplant rejeksiyonunda temel rol oynad\u0131\u011f\u0131 bilinmektedir. Bu y\u00fczden \u03b1\u03b2 T h\u00fccreleri d\u0131\u015f\u0131ndaki T h\u00fccrelerinin tedavi i\u00e7in kullan\u0131m\u0131, resept\u00f6r repertuar\u0131n\u0131n daha k\u0131s\u0131tl\u0131 olmas\u0131 sebebiyle vir\u00fcs-spesifik haf\u0131za T h\u00fccrelerinin kullan\u0131m\u0131 ve en \u00f6nemlisi gen editleme y\u00f6ntemleri kullan\u0131larak \u03b1\u03b2 T h\u00fccrelerindeki resept\u00f6rlerin silinmesi ile bu yan etkilerin g\u00f6r\u00fclme olas\u0131l\u0131\u011f\u0131n\u0131 azaltma \u00e7al\u0131\u015fmalar\u0131 da y\u00fcr\u00fct\u00fclmekte ve baz\u0131 klinik denemelerde olduk\u00e7a umut vadeden sonu\u00e7lar al\u0131nd\u0131\u011f\u0131 rapor edilmektedir.<\/p>\n\n\n\n<figure class=\"wp-block-image\"><a href=\"https:\/\/www.nature.com\/articles\/s41573-019-0051-2\/figures\/1\"><img src=\"https:\/\/media.springernature.com\/full\/springer-static\/image\/art%3A10.1038%2Fs41573-019-0051-2\/MediaObjects\/41573_2019_51_Fig1_HTML.png\" alt=\"Fig. 1\" \/><\/a><figcaption><em>Sa\u011fl\u0131kl\u0131 don\u00f6rlerden al\u0131nan kandaki T h\u00fccreleri viral vekt\u00f6rler arac\u0131l\u0131\u011f\u0131 ile CAR-T h\u00fccrelerine d\u00f6n\u00fc\u015ft\u00fcr\u00fcl\u00fcr, gen editleme ile CD52 y\u00fczey marker\u0131 y\u00fczeyden \u00e7\u0131kart\u0131l\u0131r. Amplifikasyonun ard\u0131ndan filtreleme ile T H\u00fccresi Resept\u00f6r\u00fc ta\u015f\u0131yan h\u00fccreler ay\u0131klanarak kalan h\u00fccreler dondurulur ve birden fazla hasta taraf\u0131ndan bu h\u00fccreler kullan\u0131labilir.<\/em> &#8216;Off-the-shelf&#8217; allogeneic CAR T cells: development and challenges.&nbsp;<em>Nature reviews<\/em> <a href=\"https:\/\/www.nature.com\/articles\/s41573-019-0051-2\/figures\/1\">https:\/\/www.nature.com\/articles\/s41573-019-0051-2\/figures\/1<\/a><\/figcaption><\/figure>\n\n\n\n<p><\/p>\n\n\n\n<h3>CAR-NK Tedavisi<\/h3>\n\n\n\n<p>Hastaya daha \u00f6nceden don\u00f6r kan\u0131ndan elde edilmi\u015f tedaviyi aktarabilmek i\u00e7in geli\u015ftirilmi\u015f y\u00f6ntemlerden bir tanesi de CAR-NK h\u00fccrelerinin geli\u015ftirilmesidir. NK olarak k\u0131salt\u0131lan \u201cdo\u011fal katil\u201d h\u00fccrelerimiz periferik kandaki l\u00f6kositlerin %5-15\u2019ini olu\u015fturmaktad\u0131r. Sitotoksik T h\u00fccreleri ile benzer bir fonksiyona sahip olup spesifik bir T resept\u00f6r\u00fcne sahip olmaks\u0131z\u0131n anti-t\u00fcm\u00f6r faaliyetlerini g\u00f6stermesi y\u00f6n\u00fcyle sitotoksik T h\u00fccrelerinden ayr\u0131lmaktad\u0131rlar.&nbsp; CAR-NK h\u00fccreleri, bu \u00f6zellikleri dolay\u0131s\u0131yla GvHD a\u00e7\u0131s\u0131ndan \u00e7ok daha d\u00fc\u015f\u00fck riske sahiptirler.&nbsp; Sal\u0131n\u0131m\u0131na sebep olduklar\u0131 sitokinlerin sitotoksik T h\u00fccreleri kaynakl\u0131 sal\u0131nan sitokinlerden farkl\u0131 olmas\u0131 Sitokin Sal\u0131n\u0131m Sendromu\u2019na yol a\u00e7ma ihtimallerini olduk\u00e7a d\u00fc\u015f\u00fcr\u00fcr ve n\u00f6rotoksisite yine sitokin farkl\u0131l\u0131\u011f\u0131n\u0131n etkisiyle \u00e7ok daha seyrek g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Ayr\u0131ca \u015fu an y\u00fcr\u00fct\u00fclen baz\u0131 gen editleme \u00e7al\u0131\u015fmalar\u0131 ile CAR-NK h\u00fccrelerinin solid t\u00fcm\u00f6rlere kar\u015f\u0131 da etkin hale getirilebilece\u011fi y\u00f6n\u00fcnde veriler bulunmaktad\u0131r.<\/p>\n\n\n\n<p><\/p>\n\n\n\n<p>\u00d6zetle; imm\u00fcnoterapi, hi\u00e7bir umut olmad\u0131\u011f\u0131 d\u00fc\u015f\u00fcn\u00fclen kanser hastalar\u0131na bile umut veren olduk\u00e7a etkili bir tedavi \u015fekli olmakla birlikte durmaks\u0131z\u0131n yeni imm\u00fcnoterapi metodlar\u0131 geli\u015ftiren t\u0131p d\u00fcnyas\u0131 daha fazla hasta i\u00e7in umut \u0131\u015f\u0131\u011f\u0131 yaratmaya devam etmektedir. Bu tedaviler i\u00e7erisinde en yenilerden biri olan CAR-T h\u00fccre tedavisi, hen\u00fcz FDA onay\u0131n\u0131 2017 y\u0131l\u0131nda alm\u0131\u015f olmas\u0131na ra\u011fmen daha iyi sonu\u00e7 verebilece\u011fi d\u00fc\u015f\u00fcn\u00fclen alternatif tedavilerin \u015fimdiden ortaya konmaya ba\u015flanm\u0131\u015f olmas\u0131 imm\u00fcnoterapinin ne kadar h\u0131zl\u0131 geli\u015fen bir alan oldu\u011funa dair en canl\u0131 kan\u0131tlardan biri olsa gerek. Bu t\u00fcr yenilik\u00e7i tedavilerin daha da \u00e7o\u011falmas\u0131, imm\u00fcnoterapide ilerleyi\u015fin artarak devam etmesi dile\u011fiyle!<\/p>\n\n\n\n<p><\/p>\n\n\n\n<h3>KAYNAK\u00c7A<\/h3>\n\n\n\n<p>Siegler, E. L., Zhu, Y., Wang, P., &amp; Yang, L. (2018). Off-the-Shelf CAR-NK Cells for Cancer Immunotherapy.&nbsp;<em>Cell stem cell<\/em>,&nbsp;<em>23<\/em>(2), 160\u2013161. <a href=\"https:\/\/doi.org\/10.1016\/j.stem.2018.07.007\">https:\/\/doi.org\/10.1016\/j.stem.2018.07.007<\/a><\/p>\n\n\n\n<p>Cellular therapies Program. (n.d.), from <a href=\"https:\/\/www.dana-farber.org\/cellular-therapies-program\/car-t-cell-therapy\/\">https:\/\/www.dana-farber.org\/cellular-therapies-program\/car-t-cell-therapy\/<\/a><\/p>\n\n\n\n<p>Car t cells: Engineering immune cells to treat cancer. (n.d.), from https:\/\/www.cancer.gov\/about-cancer\/treatment\/research\/car-t-cells<\/p>\n\n\n\n<p>Immunotherapy for cancer. (n.d.), from <a href=\"https:\/\/www.cancer.gov\/about-cancer\/treatment\/types\/immunotherapy#:~:text=Immunotherapy%20is%20a%20type%20of,a%20type%20of%20biological%20therapy\">https:\/\/www.cancer.gov\/about-cancer\/treatment\/types\/immunotherapy#:~:text=Immunotherapy%20is%20a%20type%20of,a%20type%20of%20biological%20therapy<\/a>.<\/p>\n\n\n\n<p>Depil, S., Duchateau, P., Grupp, S. A., Mufti, G., &amp; Poirot, L. (2020). &#8216;Off-the-shelf&#8217; allogeneic CAR T cells: development and challenges.&nbsp;<em>Nature reviews. Drug discovery<\/em>,&nbsp;<em>19<\/em>(3), 185\u2013199. <a href=\"https:\/\/doi.org\/10.1038\/s41573-019-0051-2\">https:\/\/doi.org\/10.1038\/s41573-019-0051-2<\/a><\/p>\n\n\n\n<p>Xie, G., Dong, H., Liang, Y., Ham, J. D., Rizwan, R., &amp; Chen, J. (2020). CAR-NK cells: A promising cellular immunotherapy for cancer.&nbsp;<em>EBioMedicine<\/em>,&nbsp;<em>59<\/em>, 102975. <a href=\"https:\/\/doi.org\/10.1016\/j.ebiom.2020.102975\">https:\/\/doi.org\/10.1016\/j.ebiom.2020.102975<\/a><\/p>\n\n\n\n<p>King, A. (2020). Building better CAR-T therapies, from <a href=\"https:\/\/www.nature.com\/articles\/d41586-020-02675-w\">https:\/\/www.nature.com\/articles\/d41586-020-02675-w<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>V\u00fccudumuzu her t\u00fcrl\u00fc \u201cyabanc\u0131\u201d n\u0131n zararl\u0131 etkilerinden korumak \u00fczere tasarlanm\u0131\u015f olan imm\u00fcn sistemimiz, kanser oda\u011f\u0131 geli\u015ftirmeye yatk\u0131n olan h\u00fccreleri ortadan<\/p>\n","protected":false},"author":390,"featured_media":9927,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1,25,19],"tags":[1876,1875,1878,84],"acf":[],"views":949,"_links":{"self":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/9925"}],"collection":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/users\/390"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/comments?post=9925"}],"version-history":[{"count":7,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/9925\/revisions"}],"predecessor-version":[{"id":9936,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/9925\/revisions\/9936"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media\/9927"}],"wp:attachment":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media?parent=9925"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/categories?post=9925"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/tags?post=9925"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}