PMID- 10838664
OWN - NLM
STAT- MEDLINE
DCOM- 20000816
LR  - 20191104
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 23
IP  - 3
DP  - 2000 May-Jun
TI  - Restoration of alloreactivity of melanoma by transduction with B7.1.
PG  - 353-61
AB  - Melanoma cells are unusual because, unlike most epithelial tumors, constitutive 
      expression of human leukocyte antigen (HLA) class II molecules is common. To 
      elucidate the role of HLA class II expression in the immunopathogenesis of 
      melanoma, the authors compared HLA class II+ melanoma cells to autologous B cells 
      with respect to their ability to stimulate primary (naive) histoincompatible 
      lymphocytes and T-cell clones (antigen experienced). Using primary lymphocytes 
      (peripheral blood lymphocytes [PBLs]), melanoma cells were nonstimulatory when 
      compared to autologous B cells. To determine whether this was caused by defective 
      antigen processing, the authors used alloreactive T-cell clones, which require 
      alloantigen presentation by a histocompatible stimulator cell but not 
      costimulation. Melanoma cells stimulated the alloreactive T-cell clones in two of 
      three clones tested, indicating that they processed and presented alloantigen. To 
      determine whether the failure of melanoma cells to stimulate primary lymphocytes 
      was caused by their inability to costimulate the T cells, the authors transduced 
      the melanoma cells with B7.1 and achieved stable expression in more than 95% of 
      the cells. The transduced cells were highly stimulatory, eliciting a 17- to 
      25-fold increase in proliferation by the peripheral blood lymphocytes compared 
      with controls. Indeed, B7-expressing melanoma cells were more stimulatory than 
      autologous B cells, which elicited an 11- to 15-fold increase compared with 
      controls. These data indicate that melanoma cells fail to stimulate primary 
      lymphocytes because they do not deliver costimulatory signals. Engineering HLA 
      class II+ melanoma cells to express high levels of B7.1 may provide a way to 
      elicit primary T-cell responses to melanoma-associated antigens.
FAU - Brady, M S
AU  - Brady MS
AD  - Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 
      10021, USA.
FAU - Lee, F
AU  - Lee F
FAU - Eckels, D D
AU  - Eckels DD
FAU - Ree, S Y
AU  - Ree SY
FAU - Latouche, J B
AU  - Latouche JB
FAU - Lee, J S
AU  - Lee JS
LA  - eng
GR  - AI22832/AI/NIAID NIH HHS/United States
GR  - GM50902/GM/NIGMS NIH HHS/United States
GR  - HL44612/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (B7-1 Antigen)
RN  - 0 (CD28 Antigens)
RN  - 0 (CD4 Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Isoantigens)
SB  - IM
MH  - Antibodies, Monoclonal/immunology
MH  - Antigen Presentation/immunology
MH  - Antigens, Neoplasm/immunology
MH  - B-Lymphocytes/immunology
MH  - B7-1 Antigen/genetics/*immunology
MH  - CD28 Antigens/immunology
MH  - CD4 Antigens/immunology
MH  - Cell Line, Transformed
MH  - Histocompatibility Antigens Class II/*immunology
MH  - Humans
MH  - Isoantigens/*immunology
MH  - Lymphocyte Activation
MH  - Lymphocyte Culture Test, Mixed
MH  - Melanoma/genetics/*immunology
MH  - T-Lymphocytes/*immunology
MH  - Transduction, Genetic
MH  - Tumor Cells, Cultured
EDAT- 2000/06/06 09:00
MHDA- 2000/08/19 11:00
CRDT- 2000/06/06 09:00
PHST- 2000/06/06 09:00 [pubmed]
PHST- 2000/08/19 11:00 [medline]
PHST- 2000/06/06 09:00 [entrez]
AID - 10.1097/00002371-200005000-00008 [doi]
PST - ppublish
SO  - J Immunother. 2000 May-Jun;23(3):353-61. doi: 10.1097/00002371-200005000-00008.