Thoracic duct lymphatic fluid harbors phenotypically naive T cells for use in adoptive T-cell therapy.
Cytotherapy
; 22(10): 529-535, 2020 10.
Article
in En
| MEDLINE
| ID: mdl-32622753
ABSTRACT
BACKGROUND AIMS:
Manufacturing of potent chimeric antigen receptor (CAR) T cells requires phenotypically naive and early memory T cells. We hypothesized lymphatic fluid collected from the thoracic duct of children would serve as a unique reservoir for early T cells, which could then be used for CAR T-cell therapy.METHODS:
We evaluated lymphatic fluid collected from 25 pediatric patients undergoing thoracic duct cannulation for other clinical indications.RESULTS:
Lymphatic fluid in the thoracic duct was rich in T cells, with higher percentage of naive and stem central memory T-cell subsets compared with paired blood samples. T cells from lymphatic fluid showed decreased negative checkpoint regulators on the surface and increased rapid expansion with bead activation. Creation of CD19-directed CAR T cells from blood and lymphatic T cells showed similar lentiviral transduction properties, but CAR T cells generated from lymphatic fluid produced superior cytotoxicity in a murine leukemia model because they were able to achieve equivalent tumor eradication at lower doses.CONCLUSIONS:
These results are the first characterization of T cells from the thoracic duct of pediatric patients and suggest an alternative approach for manufacturing of cellular therapy that will improve both expansion and cytotoxic effect.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Thoracic Duct
/
T-Lymphocytes
/
Immunotherapy, Adoptive
/
Lymph
Limits:
Animals
/
Child
/
Female
/
Humans
Language:
En
Journal:
Cytotherapy
Journal subject:
TERAPEUTICA
Year:
2020
Type:
Article