Obrat CAR T

OBRAT CAR T

Inštitut za mikrobiologijo in imunologijo (IMI) na Medicinske fakulteti Univerze v Ljubljani je leta 2024 vzpostavil GMP (ang. Good Manufacturing Practice)-skladen ATMP (ang. Advanced Therapy Medicinal Products) center za proizvodnjo CAR T celic, da bi zadostil povpraševanju po CAR T celični terapiji v Sloveniji. V sodelovanju s Kliničnim oddelkom za hematologijo Univerzitetnega kliničnega centra v Ljubljani je IMI ključen pri vzpostavitvi proizvodnje anti-CD19 CAR T-celic za zdravljenje akutne limfoblastne levkemije (B-ALL) in velikoceličnih B- limfomov. Center ATMP, skladen z GMP, je zgrajen modularno (172 m2 čistih prostorov v 600 m2 proizvodni hali) in omogoča z nekaj manjšimi konstrukcijskimi spremembami vzpostavitev več linij proizvodnje CAR-T celic, vključno z uporabo akademskih vektorjev v kliničnih študijah, ali za namene sočutne uporabe.

Bolnikove limfocite T se odvzame iz krvi, jih v inkubatorju okuži z vektorskimi virusi, ki prinesejo v limfocite T nov gen (CAR), ki omogoča prepoznavanje bolnikovega tumorja. Tako pripravljene “umetne limfocite T” se v inkubatorju dodatno razmnoži (2 tedna) in nato injicira v bolnika z namenom, da celice CAR-T napadejo in uničijo tumor. Sintetični receptorji CAR so oblikovani na osnovi enoverižne imunoglobulinske molekule tako, da limfocitom T omogočijo prepoznavo specifičnih tarčnih molekul na površini tumorskih celic. Za razliko od receptorjev TCR, so receptorji CAR sposobni prepoznave površinskih antigenov neodvisno od molekul poglavitnega histokompatibilnostnega kompleksa (MHC).

Več o pripravi CAR-T in zdravljenju: 11: LIKARJEV SIMPOZIJ: RAZVOJ IN UPORABA ZDRAVLJENJA S CELICAMI CAR-T

CAR T FACILITY

The Institute of Microbiology and Immunology (IMI) at the Faculty of Medicine of the University of Ljubljana established a GMP (Good Manufacturing Practice )-compliant ATMP (Advanced Therapy Medicinal Products) centre for the production of CAR T cells in 2024 to meet the demand for CAR T cell therapy in Slovenia. In collaboration with the Clinical Department of Haematology at the University Medical Centre Ljubljana, IMI is key to establishing the production of anti-CD19 CAR T-cells for the treatment of acute lymphoblastic leukaemia (B-ALL) and large B-cell lymphomas. The GMP-compliant ATMP centre has a modular design (172 m2 of clean rooms in a 600 m2 production hall) and, with some minor structural modifications, allows for the establishment of multiple CAR T cell production lines, including the use of academic vectors in clinical trials or for compassionate use purposes.

The patient’s T lymphocytes are taken from the blood and infected in an incubator with vector viruses that introduce a new gene (CAR) into the T lymphocytes so that they can recognise the patient’s tumour. The “artificial T-lymphocytes” prepared in this way are further multiplied in an incubator (2 weeks) and then injected into the patient so that the CAR T-cells attack and destroy the tumour. Synthetic CAR receptors are developed on the basis of a single-chain immunoglobulin molecule so that the T lymphocytes can recognise specific target molecules on the surface of tumour cells. In contrast to TCR receptors, CAR receptors are able to recognise surface antigens independently of molecules of the major histocompatibility complex (MHC).

More about CAR-T preparation and treatment: 11: LIKARJEV SIMPOZIJ: RAZVOJ IN UPORABA ZDRAVLJENJA S CELICAMI CAR-T