Establishment of a simple and efficient platform for car-t cell generation and expansion: from lentiviral production to in vivo studies
Hematol., Transfus. Cell Ther. (Impr.)
;
42(2): 150-158, Apr.-June 2020. tab, graf
Article
in English
| LILACS
| ID: biblio-1134018
ABSTRACT
ABSTRACT Introduction:
Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19 + B-cell malignancies in numerous clinical trials. The CAR molecule, which recognizes cell-surface tumor-associated antigen independently of human leukocyte antigen (HLA), is composed by one or more signaling molecules to activate genetically modified T cells for killing, proliferation, and cytokine production.Objectives:
In order to make this treatment available for a larger number of patients, we developed a simple and efficient platform to generate and expand CAR-T cells.Methods:
Our approach is based on a lentiviral vector composed by a second-generation CAR that signals through a 41BB and CD3-ζ endodomain.Conclusions:
In this work, we show a high-level production of the lentiviral vector, which was successfully used to generate CAR-T cells. The CAR-T cells produced were highly cytotoxic and specific against CD19+ cells in vitro and in vivo, being able to fully control disease progression in a xenograft B-cell lymphoma mouse model. Our work demonstrates the feasibility of producing CAR-T cells in an academic context and can serve as a paradigm for similar institutions. Nevertheless, the results presented may contribute favoring the translation of the research to the clinical practice.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
In Vitro Techniques
/
Immunotherapy, Adoptive
/
Antigens, CD19
/
Cytotoxicity, Immunologic
/
Heterografts
Limits:
Humans
Language:
English
Journal:
Hematol., Transfus. Cell Ther. (Impr.)
Journal subject:
Hematologia
/
TransfusÆo de Sangue
Year:
2020
Type:
Article
Affiliation country:
Brazil
Institution/Affiliation country:
Universidade de São Paulo - USP/BR
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