I-immunotherapy ekwelapheni umdlavuza
Ukwelashwa komdlavuza i-CAR-NK kunezinga elisebenzayo lama-73%, futhi kuqashwa ezinhlolweni zokwelashwa zasekhaya.
I-Immunotherapy iye yashintsha indlela umdlavuza welashwa ngayo. I-Cancer immunotherapy ihlukaniswe izigaba ezimbili: eyodwa i-immune checkpoint inhibitors, kanti i-PD-1, i-PD-L1 ne-CTLA-4 ivunyelwe ukwelashwa kwezinhlobonhlobo zomdlavuza. Futhi i-2018 Nobel Prize in Physiology noma Medicine inikeze umnikelo wokuthuthukiswa kwama-immune checkpoint inhibitors kubantu.
Enye i-cellular immunotherapy, lapho i- chimeric antigen receptor CAR-T therapy is the most rapidly progressing one. In 2017, the US Food and Drug Administration (FDA) approved two CAR-T cell therapies, Yescarta and Kymriah, which mainly target hematological tumors, leukemias and i-lymphomas.
Ukwelashwa kwe-CAR T Cell
CAR-T therapy has a long way to go to treat solid tumors, so scientists have begun to seek other cellular ama-immunotherapies to treat cancer, and natural killer (NK) cell therapy is one of the most promising methods. The success of CAR-T cell therapy has stimulated enthusiasm for modifying NK cells with CAR genes to enhance their tumor-killing ability.
Recently, the results of a phase I / IIa trial of the MD Anderson Cancer Center in the United States announced that CD19-targeted umbilical cord blood chimeric antigen receptor natural killer cell therapy (CAR-NK) has achieved a clinical response. No major toxicities were observed in patients with refractory or refractory I-non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL).
Idatha yocwaningo lokwelashwa kwamaseli e-CAR-NK
Imiphumela yecala ishicilelwe izolo kwiNew England Journal of Medicine. Ezigulini eziyi-11 ezazibambe iqhaza ocwaningweni, eziyi-8 (73%) zaphendula ekwelashweni, kanti eziyi-7 zazo zaphendula ngokuphelele, okusho ukuthi azisakhombisi izimpawu zomdlavuza ekulandeleni okuphakathi izinyanga eziyi-13.8, futhi azikho iziguli ezinama-cell I-Factor release syndrome noma i-neurotoxicity.
Impendulo ekwelashweni kwamaseli e-CD19 CAR-NK ibibalulekile kungakapheli inyanga eyodwa ngemuva kokufakwa, futhi ukuphikelela kwalawa maseli kusatholakala kungakapheli unyaka owodwa ngemuva kokufakwa.
Umbhali ofanayo uKaty Rezvani, uProfesa we-Stem Cell Transplantation and Cell Therapy, uthe: “Siyakhuthazeka ngemiphumela yocwaningo lomtholampilo, oluzokwenza izifundo ezengeziwe zokwelashwa ukuze kutholakale amandla ezinhlayiya ze-allogeneic ezitholakala ngegazi ze-CAR-NK njengoba isiguli esidinga izinketho zokwelashwa. "
E-MD Anderson Cancer Center, amangqamuzana e-NK ahlukaniswa negazi lenkaba elinikelwe futhi kwenziwa izakhi zofuzo ukuveza i-CAR edingekayo, engakhomba izinhloso eziqondene nomdlavuza. Amaseli e-CAR-NK nawo kudingeka "ahlonyiswe" nge-IL-15, i-molecule ekhombisa amasosha omzimba eyenzelwe ukuqinisa ukwanda kwamaseli nokusinda.
Kulolu cwaningo, amaseli e-CAR-NK ayi-allogeneic, okusho ukuthi lawa maseli athathwe kubaxhasi abanempilo abangahlobene nesiguli, hhayi isiguli uqobo. Ngakho-ke, amaseli e-CAR-NK anamandla okukhiqizwa futhi agcinwe kusengaphambili ukuze asetshenziswe ngokushesha. Ngokuphambene nalokho, amaseli we-CAR-T akhona manje athengiswayo adinga ukusebenzisa inqubo yokwanda kwamasiko amaningi ukukhiqiza amaseli we-T enzelwe izakhi zofuzo ngokuya ngofuzo lwesiguli.
Amaseli e-CAR-NK anezinzuzo eziningi ngaphezu kwamaseli we-CAR-T
First, unlike CAR-T cells, CAR-NK cells retain the inherent ability to recognize and target isisu cells through their natural receptors, so that when CAR-NK targeted therapy is used, tumor cells are less likely to escape killing.
Second, CAR-NK cells do not undergo immune rejection for days to weeks. As a result, they have not shown the same safety issues in many CAR-T clinical trials, such as the absence of i-cytokine release syndrome.
Ekugcineni, amangqamuzana e-NK awadingi ukufana okuqinile kwe-HLA futhi awanawo amandla okubanga isifo se-graft-versus-host, okuyingozi enkulu ye-CAR-T cell immunotherapy.
