PMID- 16569594
OWN - NLM
STAT- MEDLINE
DCOM- 20060517
LR  - 20171116
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 34
IP  - 4
DP  - 2006 Apr
TI  - Clinical grade expansion of CD45RA, CD45RO, and CD62L-positive T-cell lines from 
      HLA-compatible donors: high cytotoxic potential against AML and ALL cells.
PG  - 475-85
AB  - OBJECTIVE: Identification of a clinical grade method for the ex vivo generation 
      of donor-derived T cells cytotoxic against both myeloid and lymphoblastic cells 
      still remains elusive. We investigated rapid generation and expansion of donor 
      derived-allogeneic T-cell lines cytotoxic against patient leukemic cells. 
      MATERIALS AND METHODS: Acute myelogenous leukemia (AML) and acute lymphoblastic 
      leukemia (ALL) blasts were cultured 5 days in Stem Span, granulocyte macrophage 
      colony-stimulating factor, interleukin-4, and calcium ionophore. All B-precursor 
      ALL (N22) and AML (N13), but not T-cell ALL (N3), differentiated into mature 
      leukemia-derived antigen-presenting cells (LD-APC). All but one LD-APC generated 
      cytotoxic T lymphocyte (CTL) from adult human leukocyte antigen (HLA)-identical 
      (N8) or unrelated donors (N2). RESULTS: Upon in vitro culture, donor-derived CTL 
      acquired a memory T phenotype, showing concomitant high CD45RA, CD45RO, CD62L 
      expression. CD8(+) cells, but not CD4(+) cells, were granzyme, perforine, and 
      interferon-gamma-positive. Pooled CD4(+) and CD8(+) cells were cytotoxic against 
      leukemic blasts (32%, 30:1 E:T ratio), but not against autologous or 
      patient-derived phytohemagglutinin blasts. LD-APC from five ALL patients were 
      used to generate CTL from cord blood. A mixed population of CD4(+) and CD8(+) 
      cells was documented in 54% of wells. T cells acquired classical effector memory 
      phenotype and showed a higher cytotoxicity against leukemia blasts (47%, 1:1 E:T 
      ratio). Adult and cord blood CTL showed a skewing from a complete T-cell receptor 
      repertoire to an oligo-clonal/clonal pattern. CONCLUSIONS: Availability of these 
      cells should allow clinical trials for salvage treatment of leukemia patients 
      relapsing after allogeneic stem cell transplantation.
FAU - Barbui, Anna M
AU  - Barbui AM
AD  - Laboratorio di Terapia Cellulare e Genica G. Lanzani, Ematologia, Ospedali 
      Riuniti di Bergamo, Italy. abarbui@osepadaliriuniti.bergamo.it
FAU - Borleri, Gianmaria
AU  - Borleri G
FAU - Conti, Elena
AU  - Conti E
FAU - Ciocca, Alice
AU  - Ciocca A
FAU - Salvi, Anna
AU  - Salvi A
FAU - Mico, Caterina
AU  - Mico C
FAU - Introna, Martino
AU  - Introna M
FAU - Rambaldi, Alessandro
AU  - Rambaldi A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (HLA Antigens)
RN  - 0 (Ionophores)
RN  - 126880-86-2 (L-Selectin)
RN  - 207137-56-2 (Interleukin-4)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antigen Presentation/drug effects/immunology
MH  - Antigen-Presenting Cells/immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/*immunology/transplantation
MH  - Cell Differentiation/drug effects/immunology
MH  - Cell Line
MH  - Child, Preschool
MH  - Female
MH  - Fetal Blood/immunology
MH  - HLA Antigens/immunology
MH  - Humans
MH  - Immunologic Memory/*immunology
MH  - Immunotherapy, Adoptive/methods
MH  - Infant
MH  - Interleukin-4/pharmacology
MH  - Ionophores/pharmacology
MH  - L-Selectin/*immunology
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*immunology/therapy
MH  - Leukemia, Myeloid, Acute/*immunology/therapy
MH  - Leukocyte Common Antigens/*immunology
MH  - Living Donors
MH  - Macrophage Colony-Stimulating Factor/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Stem Cell Transplantation/methods
MH  - Transplantation, Homologous
EDAT- 2006/03/30 09:00
MHDA- 2006/05/18 09:00
CRDT- 2006/03/30 09:00
PHST- 2005/08/13 00:00 [received]
PHST- 2005/12/13 00:00 [revised]
PHST- 2005/12/13 00:00 [accepted]
PHST- 2006/03/30 09:00 [pubmed]
PHST- 2006/05/18 09:00 [medline]
PHST- 2006/03/30 09:00 [entrez]
AID - S0301-472X(05)00561-8 [pii]
AID - 10.1016/j.exphem.2005.12.012 [doi]
PST - ppublish
SO  - Exp Hematol. 2006 Apr;34(4):475-85. doi: 10.1016/j.exphem.2005.12.012.