PMID- 31676276
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210110
IS  - 2531-1387 (Electronic)
IS  - 2531-1379 (Print)
IS  - 2531-1379 (Linking)
VI  - 42
IP  - 2
DP  - 2020 Apr-Jun
TI  - Establishment of a simple and efficient platform for car-t cell generation and 
      expansion: from lentiviral production to in vivo studies.
PG  - 150-158
LID - S2531-1379(19)30135-X [pii]
LID - 10.1016/j.htct.2019.06.007 [doi]
AB  - 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-zeta 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.
CI  - Copyright (c) 2019 Associacao Brasileira de Hematologia, Hemoterapia e Terapia 
      Celular. Published by Elsevier Editora Ltda. All rights reserved.
FAU - Picanco-Castro, Virginia
AU  - Picanco-Castro V
AD  - Universidade de Sao Paulo (USP), Hemocentro, Centro de Terapia Celular CTC, 
      Ribeirao Preto, SP, Brazil. Electronic address: 
      virginia.picanco@hemocentro.fmrp.usp.br.
FAU - Moco, Pablo Diego
AU  - Moco PD
AD  - Universidade de Sao Paulo (USP), Hemocentro, Centro de Terapia Celular CTC, 
      Ribeirao Preto, SP, Brazil.
FAU - Mizukami, Amanda
AU  - Mizukami A
AD  - Universidade de Sao Paulo (USP), Hemocentro, Centro de Terapia Celular CTC, 
      Ribeirao Preto, SP, Brazil.
FAU - Vaz, Leticia Delfini
AU  - Vaz LD
AD  - Universidade de Sao Paulo (USP), Hemocentro, Centro de Terapia Celular CTC, 
      Ribeirao Preto, SP, Brazil.
FAU - de Souza Fernandes Pereira, Marcelo
AU  - de Souza Fernandes Pereira M
AD  - Universidade de Sao Paulo (USP), Hemocentro, Centro de Terapia Celular CTC, 
      Ribeirao Preto, SP, Brazil.
FAU - Silvestre, Renata Nacasaki
AU  - Silvestre RN
AD  - Universidade de Sao Paulo (USP), Hemocentro, Centro de Terapia Celular CTC, 
      Ribeirao Preto, SP, Brazil.
FAU - de Azevedo, Julia Teixeira Cottas
AU  - de Azevedo JTC
AD  - Universidade de Sao Paulo (USP), Hemocentro, Centro de Terapia Celular CTC, 
      Ribeirao Preto, SP, Brazil.
FAU - de Sousa Bomfim, Aline
AU  - de Sousa Bomfim A
AD  - Universidade de Sao Paulo (USP), Hemocentro, Centro de Terapia Celular CTC, 
      Ribeirao Preto, SP, Brazil.
FAU - de Abreu Neto, Mario Soares
AU  - de Abreu Neto MS
AD  - Universidade de Sao Paulo (USP), Hemocentro, Centro de Terapia Celular CTC, 
      Ribeirao Preto, SP, Brazil.
FAU - Malmegrim, Kelen Cristina Ribeiro
AU  - Malmegrim KCR
AD  - Universidade de Sao Paulo (USP), Hemocentro, Centro de Terapia Celular CTC, 
      Ribeirao Preto, SP, Brazil; Universidade de Sao Paulo, Faculdade de Ciencias 
      Farmaceuticas de Ribeirao Preto da Ribeirao Preto (FCFRP), SP, Brazil.
FAU - Swiech, Kamilla
AU  - Swiech K
AD  - Universidade de Sao Paulo (USP), Hemocentro, Centro de Terapia Celular CTC, 
      Ribeirao Preto, SP, Brazil; Universidade de Sao Paulo, Faculdade de Ciencias 
      Farmaceuticas de Ribeirao Preto da Ribeirao Preto (FCFRP), SP, Brazil.
FAU - Covas, Dimas Tadeu
AU  - Covas DT
AD  - Universidade de Sao Paulo (USP), Hemocentro, Centro de Terapia Celular CTC, 
      Ribeirao Preto, SP, Brazil; Universidade de Sao Paulo, Faculdade de Medicina de 
      Ribeirao Preto da Ribeirao Preto (FMRP-USP), SP, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20191009
PL  - Brazil
TA  - Hematol Transfus Cell Ther
JT  - Hematology, transfusion and cell therapy
JID - 101725732
PMC - PMC7248496
OTO - NOTNLM
OT  - CAR-T cells
OT  - CD19
OT  - Cell expansion
OT  - Cytotoxicity
OT  - Immunotherapy
OT  - In vitro
OT  - In vivo xenograft model
OT  - Lentiviral vector production
EDAT- 2019/11/05 06:00
MHDA- 2019/11/05 06:01
PMCR- 2019/10/09
CRDT- 2019/11/03 06:00
PHST- 2019/03/28 00:00 [received]
PHST- 2019/06/10 00:00 [accepted]
PHST- 2019/11/05 06:00 [pubmed]
PHST- 2019/11/05 06:01 [medline]
PHST- 2019/11/03 06:00 [entrez]
PHST- 2019/10/09 00:00 [pmc-release]
AID - S2531-1379(19)30135-X [pii]
AID - 10.1016/j.htct.2019.06.007 [doi]
PST - ppublish
SO  - Hematol Transfus Cell Ther. 2020 Apr-Jun;42(2):150-158. doi: 
      10.1016/j.htct.2019.06.007. Epub 2019 Oct 9.