{"id":4278,"date":"2025-04-29T18:29:23","date_gmt":"2025-04-29T18:29:23","guid":{"rendered":"https:\/\/haber360.com\/index.php\/2025\/04\/29\/sant-paunun-yeni-car-t-tedavisi-refrakter-lenfomada\/"},"modified":"2025-04-29T18:29:23","modified_gmt":"2025-04-29T18:29:23","slug":"sant-paunun-yeni-car-t-tedavisi-refrakter-lenfomada","status":"publish","type":"post","link":"https:\/\/haber360.com\/index.php\/2025\/04\/29\/sant-paunun-yeni-car-t-tedavisi-refrakter-lenfomada\/","title":{"rendered":"Sant Pau&#8217;nun Yeni CAR-T Tedavisi Refrakter Lenfomada"},"content":{"rendered":"<p>\u0130mm\u00fcnoterapi alan\u0131nda hematolojik onkolojiye y\u00f6nelik \u00f6nemli bir ad\u0131m at\u0131ld\u0131. Barselona\u2019da bulunan Sant Pau Ara\u015ft\u0131rma Enstit\u00fcs\u00fc (IR Sant Pau) ile Hospital de Sant Pau ve Josep Carreras L\u00f6semi Ara\u015ft\u0131rma Enstit\u00fcs\u00fc i\u015f birli\u011fiyle geli\u015ftirilen yeni CAR-T h\u00fccre terapisi HSP-CAR30, CD30 antijenine \u00f6zg\u00fc hedeflemesiyle refrakter (tedaviye diren\u00e7li) CD30 pozitif lenfomalarda \u00e7\u0131\u011f\u0131r a\u00e7an sonu\u00e7lar verdi. Yak\u0131n zamanda tamamlanan Faz I klinik \u00e7al\u0131\u015fman\u0131n sonu\u00e7lar\u0131, sayg\u0131n bilimsel dergi Blood\u2019da yay\u0131mlanarak terapinin etkinli\u011fi ve g\u00fcvenilirli\u011fine dikkat \u00e7ekti. Tedavinin en \u00f6nemli \u00f6zelli\u011fi ise, haf\u0131za T h\u00fccrelerinin art\u0131\u015f\u0131na katk\u0131 sa\u011flamak suretiyle kal\u0131c\u0131 remisyonda (hastal\u0131\u011f\u0131n gerilemesi) etkin bir rol \u00fcstlenmesi oldu.<\/p>\n<p>Klasik Hodgkin lenfoma ve di\u011fer CD30-ekspresyonlu lenfomalar, \u00f6zellikle standart tedavi protokollerine yan\u0131t vermeyen veya tekrarlayan hastalarda b\u00fcy\u00fck bir tedavi zorlu\u011fu olmaya devam ediyor. CAR-T h\u00fccre terapileri, B h\u00fccreli malignitelere kar\u015f\u0131 \u00f6nemli ilerlemeler sa\u011flarken, CD30 pozitif lenfomalar\u0131n tedavisinde bu teknolojinin adaptasyonu g\u00fc\u00e7l\u00fcklerle kar\u015f\u0131la\u015ft\u0131. Bunlar\u0131n en \u00f6nemlileri, CAR-T h\u00fccrelerinin hastada kal\u0131c\u0131 olamamas\u0131 ve hastal\u0131\u011f\u0131n erken n\u00fcks\u00fc oldu. Alanda bu \u00f6zel lenfomalara y\u00f6nelik k\u0131s\u0131tl\u0131 klinik veri bulunmas\u0131 ilerlemeyi yava\u015flatt\u0131.<\/p>\n<p>IR Sant Pau ara\u015ft\u0131rma ekibi, genetik m\u00fchendislik tekniklerini ileri d\u00fczeyde kullanarak bu engelleri a\u015fmay\u0131 hedefledi. Ortaya \u00e7\u0131kan HSP-CAR30, CAR-T h\u00fccrelerinin hem uzun \u00f6m\u00fcrl\u00fc olmalar\u0131n\u0131 hem de t\u00fcm\u00f6r h\u00fccrelerine kar\u015f\u0131 etkin bir \u015fekilde sava\u015fmalar\u0131n\u0131 sa\u011flayacak \u015fekilde optimize edildi. \u00d6nemli bir yenilik olarak CD30 proteininin daha stabil ve t\u00fcm\u00f6r ka\u00e7\u0131\u015f\u0131n\u0131 \u00f6nleyen bir epitopuna odaklan\u0131ld\u0131. Bu kritik epitope y\u00f6nelik tasar\u0131m, \u00f6nceki terapilerin ba\u015far\u0131s\u0131zl\u0131k nedenlerini molek\u00fcler d\u00fczeyde a\u00e7\u0131\u011fa kavu\u015fturan detayl\u0131 yap\u0131sal analizler \u0131\u015f\u0131\u011f\u0131nda ger\u00e7ekle\u015ftirildi.<\/p>\n<p>Faz I \u00e7al\u0131\u015fmaya, tekrarlayan ya da refrakter klasik Hodgkin lenfoma veya CD30 pozitif T h\u00fccreli lenfoma tan\u0131s\u0131 konmu\u015f 10 hasta dahil edildi. Sonu\u00e7lar \u015fa\u015f\u0131rt\u0131c\u0131 derecede iyiydi: hastalar\u0131n tamam\u0131nda (%100) en az\u0131ndan k\u0131smi bir yan\u0131t elde edildi. Bunlar\u0131n yar\u0131s\u0131 ise tamamlay\u0131c\u0131 g\u00f6r\u00fcnt\u00fcleme ve ayr\u0131nt\u0131l\u0131 klinik incelemelerle kesinle\u015fen tam remisyonda bulunuyordu. IR Sant Pau Hematolojik Onkoloji Direkt\u00f6r\u00fc ve \u00e7al\u0131\u015fman\u0131n lideri Dr. Javier Briones, bu benzersiz etkinin HSP-CAR30\u2019un g\u00fc\u00e7l\u00fc imm\u00fcn arac\u0131l\u0131 t\u00fcm\u00f6r bask\u0131lama kapasitesinin bir g\u00f6stergesi oldu\u011funu belirtti.<\/p>\n<p>Tedavinin bir di\u011fer \u00f6nemli ba\u015far\u0131s\u0131 da yan\u0131tlar\u0131n uzun s\u00fcre devam etmesi oldu. Kat\u0131l\u0131mc\u0131lar\u0131n %60\u2019\u0131, ortalama 34 ayl\u0131k takipte remisyonda kald\u0131. Bu s\u00fcrd\u00fcr\u00fclebilir hastal\u0131k kontrol\u00fc, HSP-CAR30\u2019un hastalarda uzun \u00f6m\u00fcrl\u00fc merkezi haf\u0131za (TCM) ve k\u00f6k h\u00fccre benzeri haf\u0131za (TSCM-like) T h\u00fccre alt tiplerinin olu\u015fumunu desteklemesiyle korelasyon g\u00f6sterdi. Bu h\u00fccreler, kal\u0131c\u0131 imm\u00fcno-g\u00f6zetim i\u00e7in hayati \u00f6neme sahiptir. Ayr\u0131ca \u00e7o\u011fu hastada, inf\u00fczyondan bir y\u0131l sonra bile CAR30 pozitif h\u00fccrelerin varl\u0131\u011f\u0131 tespit edildi. Bu durum, \u00f6nceki CAR-T \u00fcr\u00fcnlerinin ya\u015fad\u0131\u011f\u0131 erken t\u00fckenmeye kar\u015f\u0131 \u00f6nemli bir klinik ilerleme anlam\u0131na geliyor.<\/p>\n<p>G\u00fcvenlik de\u011ferlendirmeleri de umut vericiydi. Hastalar\u0131n \u00e7o\u011fu sadece hafif (1. derece) sitokin sal\u0131n\u0131m sendromu (CRS) ya\u015farken, n\u00f6rotoksisite g\u00f6r\u00fclmedi. Doz s\u0131n\u0131rlay\u0131c\u0131 yan etkilerin olmamas\u0131 terapinin klinik uygulama a\u00e7\u0131s\u0131ndan g\u00fcvenilir oldu\u011funun \u00f6nemli bir i\u015faretidir. Bu a\u00e7\u0131dan, \u00f6zellikle refrakter lenfoma hastalar\u0131n\u0131n genel olarak k\u0131r\u0131lgan sa\u011fl\u0131k durumlar\u0131 g\u00f6z \u00f6n\u00fcne al\u0131nd\u0131\u011f\u0131nda HSP-CAR30 tedavisinin uygulanabilirli\u011fi artmaktad\u0131r.<\/p>\n<p>Tedavinin ba\u015far\u0131s\u0131nda kullan\u0131lan yenilik\u00e7i \u00fcretim s\u00fcreci de kritik bir rol oynuyor. T h\u00fccrelerinin ex vivo (v\u00fccut d\u0131\u015f\u0131) \u00e7o\u011falt\u0131lmas\u0131 a\u015famas\u0131nda IL-7, IL-15 ve IL-21 interl\u00f6kinlerinin kombine edilmesi sayesinde, daha az farkl\u0131la\u015fm\u0131\u015f haf\u0131za T h\u00fccrelerinin selektif olarak \u00e7o\u011falt\u0131lmas\u0131 sa\u011fland\u0131. Bu sayede inf\u00fczyondan sonra daha y\u00fcksek \u00e7o\u011falma kapasitesine ve uzun \u00f6mre sahip T h\u00fccreleri elde edildi. Bu strateji, HSP-CAR30\u2019un antit\u00fcm\u00f6r etkinli\u011fini art\u0131r\u0131p, ba\u011f\u0131\u015f\u0131kl\u0131k sisteminin erken yorulmas\u0131 problemine kar\u015f\u0131 \u00e7\u00f6z\u00fcm sunmaktad\u0131r.<\/p>\n<p>Ayn\u0131 zamanda CD30 antijeninin stabil, ve d\u00f6k\u00fclmeyen bir epitopuna y\u00f6nelik hedefleme ile t\u00fcm\u00f6r h\u00fccrelerinin imm\u00fcn ka\u00e7\u0131\u015f mekanizmalar\u0131 engellendi. \u00d6nceki nesil CAR-T terapileri genellikle ekstrasel\u00fcler, par\u00e7alanmaya a\u00e7\u0131k b\u00f6lgelere y\u00f6nelik tasarlanm\u0131\u015ft\u0131; bu da t\u00fcm\u00f6r\u00fcn bu b\u00f6lgeleri kaybederek tedaviden kurtulmas\u0131na sebep oluyordu. HSP-CAR30\u2019un bu yap\u0131sal biyoloji bazl\u0131 epitope y\u00f6nelik tasar\u0131m\u0131 ise tedavinin ba\u015far\u0131s\u0131ndaki ak\u0131ll\u0131 m\u00fchendislik ad\u0131m\u0131d\u0131r.<\/p>\n<p>Faz I \u00e7al\u0131\u015fman\u0131n ard\u0131ndan Faz II klinik \u00e7al\u0131\u015fmalar da h\u0131zla ilerliyor. \u015eu ana kadar 32 hasta HSP-CAR30 ile tedavi edildi; ek olarak 10 hastal\u0131k bir kohort ile veri sa\u011flam kontroller devam ediyor. \u0130lk bulgular, hastalar\u0131n %55\u2019inden fazlas\u0131n\u0131n tam remisyonda oldu\u011funu g\u00f6steriyor. Bu veriler, Faz I sonu\u00e7lar\u0131n\u0131 do\u011frulamakta ve tedavinin etkinli\u011fi konusunda artan g\u00fcveni desteklemektedir. Bu deneme geni\u015fletilerek daha heterojen hasta gruplar\u0131nda terapinin genellenebilirli\u011fi ara\u015ft\u0131r\u0131lmaktad\u0131r.<\/p>\n<p>Uzmanlar, bu tedavinin refrakter CD30 pozitif lenfomalar\u0131n y\u00f6netiminde paradigmay\u0131 de\u011fi\u015ftirebilece\u011fine inan\u0131yor. \u00c7al\u0131\u015fma ekibinden Hematoloji Uzman\u0131 Dr. Ana Caballero, bu olumlu sonu\u00e7lar\u0131n ileri a\u015fama \u00e7al\u0131\u015fmalarla do\u011frulanmas\u0131 durumunda, HSP-CAR30&#8217;un standart tedavi se\u00e7ene\u011fi olabilece\u011fini belirtiyor. Hem y\u00fcksek etkili h\u00fccresel toksisiteyi hem de uzun vadeli immunolojik haf\u0131zay\u0131 bir arada sunmas\u0131, terapiyi kal\u0131c\u0131 \u015fifa sa\u011flayan bir platform haline getiriyor.<\/p>\n<p>\u00dcretim s\u00fcrecinde kalite kontrol inovasyonlar\u0131 da terapinin ba\u015far\u0131s\u0131ndaki kritik unsurlardan biri. \u00dcretim Kalite Sorumlusu Dr. Laura Escrib\u00e0, titiz \u00fcretim standartlar\u0131 ve geli\u015fmi\u015f h\u00fccre k\u00fclt\u00fcr tekniklerinin, fonksiyonel ve uzun \u00f6m\u00fcrl\u00fc CAR-T h\u00fccrelerinin y\u00fcksek verimde \u00fcretilmesini m\u00fcmk\u00fcn k\u0131ld\u0131\u011f\u0131n\u0131 vurgulad\u0131. Bu, hem klinik uygulama hem de geni\u015f \u00e7apta eri\u015filebilir off-the-shelf (haz\u0131r) tedavi \u00fcr\u00fcnleri i\u00e7in b\u00fcy\u00fck \u00f6nem ta\u015f\u0131yor.<\/p>\n<p>Projenin ilerlemesi ve ba\u015far\u0131s\u0131, \u00e7ok sekt\u00f6rl\u00fc i\u015f birli\u011fi ve finansal deste\u011fe de ba\u011fl\u0131 oldu. Josep Carreras Vakf\u0131 ve L\u00f6semi Ara\u015ft\u0131rma Enstit\u00fcs\u00fc, bu \u00e7al\u0131\u015fmaya altyap\u0131 ve finansal anlamda g\u00fc\u00e7l\u00fc katk\u0131lar sa\u011flad\u0131; Sant Pau\u2019da son teknoloji h\u00fccre \u00fcretim birimlerinin kurulmas\u0131nda rol oynad\u0131. Ayr\u0131ca La Marat\u00f3 de TV3, \u201cLa Caixa\u201d Vakf\u0131, Carlos III Sa\u011fl\u0131k Enstit\u00fcs\u00fc ve Avrupa Birli\u011fi fonlar\u0131 destekleriyle en geli\u015fmi\u015f imm\u00fcnoterapi ara\u015ft\u0131rmalar\u0131 h\u0131z kazand\u0131. Bu ortakl\u0131klar, modern onkolojide yat\u0131r\u0131mlar\u0131n klinik yeniliklere d\u00f6n\u00fc\u015f\u00fcm\u00fcn\u00fc simgeliyor.<\/p>\n<p>Sonu\u00e7 olarak HSP-CAR30, molek\u00fcler m\u00fchendislik, imm\u00fcnoloji ve klinik uzmanl\u0131\u011f\u0131 harmanlayarak lenfoma tedavisindeki uzun s\u00fcredir s\u00fcregelen engelleri a\u015fmay\u0131 hedefliyor. Haf\u0131za h\u00fccresi zengin, hedefe \u00f6zg\u00fc optimize edilerek t\u00fcm\u00f6r ka\u00e7\u0131\u015f yollar\u0131n\u0131 kapatan bu h\u00fccresel terapi, refrakter CD30 pozitif lenfoma hastalar\u0131na yeni bir umut \u0131\u015f\u0131\u011f\u0131 sunuyor. \u00d6n\u00fcm\u00fczdeki s\u00fcre\u00e7te daha geni\u015f hasta gruplar\u0131nda yap\u0131lacak \u00e7al\u0131\u015fmalar, bu yeni nesil tedavinin uzun d\u00f6nemde remisyon ve sa\u011fkal\u0131m \u00fczerindeki ger\u00e7ek klinik kazan\u0131mlar\u0131n\u0131 ortaya koyacak.<\/p>\n<p>&#8212;<\/p>\n<p><strong>Ara\u015ft\u0131rma Konusu<\/strong>: People<br \/>\n<strong>Makale Ba\u015fl\u0131\u011f\u0131<\/strong>: HSP-CAR30 with a high proportion of less-differentiated T cells promotes durable responses in refractory CD30+ lymphoma<br \/>\n<strong>Haberin Yay\u0131n Tarihi<\/strong>: 29-Apr-2025<br \/>\n<strong>Web References<\/strong>: http:\/\/dx.doi.org\/10.1182\/blood.2024026758<br \/>\n<strong>Doi Referans<\/strong>: 10.1182\/blood.2024026758<br \/>\n<strong>Anahtar Kelimeler<\/strong>: cancer treatment breakthroughs, CAR-T Cell Therapy, CD30 antigen targeting, durable therapeutic remission, hematologic oncology advancements, Hodgkin lymphoma challenges, HSP-CAR30 clinical trial, innovative immunotherapy approaches, lymphoid malignancies research, memory T cell expansion, refractory lymphoma treatment, Sant Pau Research Institute findings<\/p>\n","protected":false},"excerpt":{"rendered":"<p>\u0130mm\u00fcnoterapi alan\u0131nda hematolojik onkolojiye y\u00f6nelik \u00f6nemli bir ad\u0131m at\u0131ld\u0131. Barselona\u2019da bulunan Sant Pau Ara\u015ft\u0131rma Enstit\u00fcs\u00fc (IR Sant Pau) ile Hospital de Sant Pau ve Josep Carreras L\u00f6semi Ara\u015ft\u0131rma Enstit\u00fcs\u00fc i\u015f birli\u011fiyle geli\u015ftirilen yeni CAR-T h\u00fccre terapisi HSP-CAR30, CD30 antijenine \u00f6zg\u00fc hedeflemesiyle refrakter (tedaviye diren\u00e7li) CD30 pozitif lenfomalarda \u00e7\u0131\u011f\u0131r a\u00e7an sonu\u00e7lar verdi. Yak\u0131n zamanda tamamlanan Faz&#8230;<\/p>\n","protected":false},"author":1,"featured_media":4279,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_yoast_wpseo_title":"","_yoast_wpseo_metadesc":"","_yoast_wpseo_focuskw":"","rank_math_title":"","rank_math_description":"","rank_math_focus_keyword":"","_wpan_schema_json_ld":"","_wpan_ai_seo_metadata":"","_wpan_ai_seo_status":"","_wpan_ai_seo_policy":"","_wpan_ai_seo_faq_block":"","_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[28],"tags":[4199,4198,4197,4196,4195],"tmauthors":[],"class_list":{"0":"post-4278","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-kanser","8":"tag-hematolojik-onkolojide-car-t-yenilikleri","9":"tag-hodgkin-lenfoma-car-t-hucre-terapisi","10":"tag-hsp-car30-immunoterapi-calismasi","11":"tag-refrakter-cd30-pozitif-lenfoma-tedavisi","12":"tag-sant-pau-car-t-tedavisi"},"jetpack_featured_media_url":"https:\/\/haber360.com\/wp-content\/uploads\/2025\/04\/Sant-Pau8217nun-Yeni-CAR-T-Tedavisi-Refrakter-Lenfomada-1745951367.jpg","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/haber360.com\/index.php\/wp-json\/wp\/v2\/posts\/4278","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/haber360.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/haber360.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/haber360.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/haber360.com\/index.php\/wp-json\/wp\/v2\/comments?post=4278"}],"version-history":[{"count":0,"href":"https:\/\/haber360.com\/index.php\/wp-json\/wp\/v2\/posts\/4278\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/haber360.com\/index.php\/wp-json\/wp\/v2\/media\/4279"}],"wp:attachment":[{"href":"https:\/\/haber360.com\/index.php\/wp-json\/wp\/v2\/media?parent=4278"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/haber360.com\/index.php\/wp-json\/wp\/v2\/categories?post=4278"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/haber360.com\/index.php\/wp-json\/wp\/v2\/tags?post=4278"},{"taxonomy":"tmauthors","embeddable":true,"href":"https:\/\/haber360.com\/index.php\/wp-json\/wp\/v2\/tmauthors?post=4278"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}