PMID- 12393717
OWN - NLM
STAT- MEDLINE
DCOM- 20030128
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 100
IP  - 13
DP  - 2002 Dec 15
TI  - Chimeric IgA antibodies against HLA class II effectively trigger lymphoma cell 
      killing.
PG  - 4574-80
AB  - Antibodies against human leukocyte antigen (HLA) class II, such as 1D10 or Lym-1, 
      are currently being evaluated for the treatment of B-cell lymphomas. Previous 
      studies have demonstrated that, in addition to IgG Fc receptors, the human 
      myeloid IgA receptor (Fc(alpha)RI, CD89) also effectively triggered tumor cell 
      killing. Therefore, we used the variable light and heavy chain sequences from 
      another murine anti-HLA class II hybridoma, F3.3, to generate a panel of chimeric 
      human/mouse antibodies, including human immunoglobulin A1 (IgA1), IgA2, IgG1, 
      IgG2, IgG3, and IgG4. Antibody production was accomplished by stable transfection 
      of baby hamster kidney cells, and binding activity and specificity were confirmed 
      by enzyme-linked immunosorbent assay (ELISA) and Western blotting. All constructs 
      demonstrated similar binding to HLA class II. Functional studies revealed that 
      chimeric IgG1, IgA1, and IgA2 triggered similar levels of tumor cell lysis. 
      Analyses of effector populations, however, demonstrated that killing by chimeric 
      IgG1 constructs was triggered mainly by human mononuclear cells and complement, 
      while IgA1 and IgA2 mediated effective lysis by polymorphonuclear neutrophils. 
      Importantly, IgG1 and both IgA isotypes were equally effective at killing freshly 
      isolated human chronic lymphocytic leukemia cells. Chimeric IgA antibodies 
      against HLA class II may constitute attractive reagents for lymphoma therapy.
FAU - Dechant, Michael
AU  - Dechant M
AD  - Division of Hematology/Oncology, Department of Medicine III, University 
      Erlangen-Nurnberg, Erlangen, Germany.
FAU - Vidarsson, Gestur
AU  - Vidarsson G
FAU - Stockmeyer, Bernhard
AU  - Stockmeyer B
FAU - Repp, Roland
AU  - Repp R
FAU - Glennie, Martin J
AU  - Glennie MJ
FAU - Gramatzki, Martin
AU  - Gramatzki M
FAU - van De Winkel, Jan G J
AU  - van De Winkel JG
FAU - Valerius, Thomas
AU  - Valerius T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20020808
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Immunoglobulin A)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - Animals
MH  - *Antibody-Dependent Cell Cytotoxicity
MH  - Blotting, Western
MH  - Burkitt Lymphoma/pathology
MH  - Cell Line
MH  - Cricetinae
MH  - Enzyme-Linked Immunosorbent Assay
MH  - HLA-DR Antigens/genetics/*immunology
MH  - Humans
MH  - Immunoglobulin A/*immunology
MH  - Immunoglobulin G/*immunology
MH  - Kidney/cytology
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/pathology
MH  - Lymphoma/*pathology
MH  - Mesocricetus
MH  - Mice
MH  - Monocytes/immunology
MH  - Neutrophils/immunology
MH  - Recombinant Fusion Proteins/immunology
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 2002/10/24 04:00
MHDA- 2003/01/29 04:00
CRDT- 2002/10/24 04:00
PHST- 2002/10/24 04:00 [pubmed]
PHST- 2003/01/29 04:00 [medline]
PHST- 2002/10/24 04:00 [entrez]
AID - S0006-4971(20)53666-5 [pii]
AID - 10.1182/blood-2002-03-0687 [doi]
PST - ppublish
SO  - Blood. 2002 Dec 15;100(13):4574-80. doi: 10.1182/blood-2002-03-0687. Epub 2002 
      Aug 8.