CAR-T stanična imunoterapija u liječenju tumora i autoimunih bolesti

undergraduate thesis

• Title (english): CAR-T cell immunotherapy in the treatment of tumors and autoimmune diseases
• Author: Viktoria Krajc
• Mentor: Nada Oršolić (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-09-13, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

CAR-T stanična terapija oblik je adoptivne T-stanične imunoterapije. CAR se sastoji od 3 domene:
unutarstanične, transmembranske i izvanstanične. Unutarstanična domena prepoznaje ciljni
antigen. Transmembranska domena povezuje druge dvije domene. Izvanstanična domena daje
signale za aktivaciju limfocita nakon vezanja na antigen i na temelju nje se stanice CAR-T dijele u
5 generacija. Sam proces terapije je zahtjevan i skup, no potrebna je samo jedna doza. Započinje
leukaferezom i selekcijom željenih limfocita T, slijedi unos trangena za CAR i ekspanzija stanica
ex vivo pomoću citokina, a završava reinfuzijom stanica u osobu. Najdjelotvornija je u liječenju
hematoloških maligniteta te je za takve karcinome FDA odobrila 6 terapija, od kojih četiri imaju
dizajniran CAR za prepoznavanje CD19, a dvije BCMA. Za liječenje solidnih tumora intenzivno
se odvija veliki broj pretkliničkih i kliničkih istraživanja, a problemi se nalaze u pronalasku
odgovarajućeg ciljnog antigena, dopremanju stanica CAR-T do središta tumora i
imunosupresivnom tumorskom mikrookolišu. U novije vrijeme, sve se više pozornosti pridaje i
primjeni CAR-T terapije za liječenje autoimunih bolesti. S jedne strane se razvija CAAR-T
stanična imunoterapija, kojoj je cilj specifično eliminirati autoreaktivne limfocite B, a s druge
CAR-Treg, koja je cilj povratak imunosne tolerancije.

Abstract (english)

CAR-T cell therapy is a form of adoptive T-cell immunotherapy. CAR consists of 3 domains:
intracellular, transmembrane and extracellular. Intracellular domain recognizes the target antigen.
Transmembrane domain connects the other two domains. Extracellular domain provides signals
for the activation of lymphocytes after binding to the antigen, and based on it, CAR-T cells are
divided into 5 generations. The therapy process itself is demanding and expensive, but only one
dose is needed. It begins with leukapheresis and selection of the desired T lymphocytes, followed
by the introduction of the CAR transgene and expansion of cells ex vivo using cytokines, ending
with the reinfusion of cells into the individual. It is most effective in the treatment of hematological
malignancies, and for such cancers, the FDA has approved 6 therapies, four of which are designed
with CARs targeting CD19 and two targeting BCMA. For the treatment of solid tumors, many
preclinical and clinical studies are intensively carried out, with challenges in finding the appropriate
target antigen, delivering CAR-T cells to the tumor site and dealing with the immunosuppressive
tumor microenvironment. Recently, more and more attention has been given to the application of
CAR-T therapy for treating autoimmune diseases. On the one hand, CAAR-T cell immunotherapy
is being developed, the goal of which is to specifically eliminate autoreactive B lymphocytes, and
on the other, CAR-Treg, which aims to restore the immunological tolerance.

• Keywords: limfociti T; rak; hematološki maligniteti; autoimunost
• Keywords (english): T lymphocites; cancer; hematologic malignacies; autoimmunity
• Language: croatian
• URN:NBN: urn:nbn:hr:217:793107
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-09-15 08:39:49