PMID- 12766879
OWN - NLM
STAT- MEDLINE
DCOM- 20040304
LR  - 20191107
IS  - 1083-8791 (Print)
IS  - 1083-8791 (Linking)
VI  - 9
IP  - 5
DP  - 2003 May
TI  - Role of tumor necrosis factor-alpha in graft-versus-host disease and 
      graft-versus-leukemia responses.
PG  - 292-303
AB  - Tumor necrosis factor-alpha (TNF-alpha) antagonist therapy has proven effective 
      in inflammatory conditions such as rheumatoid arthritis and Crohn's disease. 
      There is substantial evidence that TNF-alpha also plays a role in the development 
      of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell 
      transplantation, which along with leukemia relapse remains one of the 2 major 
      impediments to success of the approach. Using a recently developed potent 
      rat/mouse chimeric monoclonal antibody directed against murine TNF-alpha 
      (CNTO2213), the authors investigated the effect of TNF-alpha blockade on GVHD 
      mediated by either CD4(+) or CD8(+) donor T cells. The results indicated that the 
      treatment had only a moderate effect on both a CD8(+) T cell-mediated major 
      histocompatibility complex-matched GVHD model involving multiple minor 
      histocompatibility antigens and a p-->F(1) acute GVHD model directed against a 
      haplo-mismatched major histocompatibility complex barrier involving both CD4(+) 
      and CD8(+) T cells. In contrast, treatment with the anti-TNF-alpha antibody had a 
      highly significant effect (100% survival rate) on the CD4(+) T cell-mediated 
      component of this latter model. Importantly, anti-TNF-alpha antibody did not 
      block the development of a graft-versus-leukemia effect against a murine myeloid 
      leukemia challenge in either a syngeneic or allogeneic p-->F(1) setting. This 
      suggests that the inhibition of TNF-alpha during allogeneic hematopoietic cell 
      transplantation may be able to diminish the inflammatory GVHD reaction without 
      hindering effective graft-versus-leukemia responses.
FAU - Korngold, Robert
AU  - Korngold R
AD  - Kimmel Cancer Institute, Jefferson Medical College, Philadelphia, Pennsylvania 
      19107, USA. R.Korngold@mail.jci.tju.edu
FAU - Marini, Joseph C
AU  - Marini JC
FAU - de Baca, Monica E
AU  - de Baca ME
FAU - Murphy, George F
AU  - Murphy GF
FAU - Giles-Komar, Jill
AU  - Giles-Komar J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biol Blood Marrow Transplant
JT  - Biology of blood and marrow transplantation : journal of the American Society for 
      Blood and Marrow Transplantation
JID - 9600628
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Bone Marrow Transplantation/adverse effects/immunology
MH  - CD4-Positive T-Lymphocytes/immunology/transplantation
MH  - CD8-Positive T-Lymphocytes/immunology/transplantation
MH  - Graft vs Host Disease/drug therapy/*prevention & control
MH  - Graft vs Leukemia Effect/*drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Recombinant Fusion Proteins/pharmacology
MH  - Survival Rate
MH  - Tumor Necrosis Factor-alpha/immunology/*physiology
EDAT- 2003/05/27 05:00
MHDA- 2004/03/05 05:00
CRDT- 2003/05/27 05:00
PHST- 2003/05/27 05:00 [pubmed]
PHST- 2004/03/05 05:00 [medline]
PHST- 2003/05/27 05:00 [entrez]
AID - S1083879103000879 [pii]
AID - 10.1016/s1083-8791(03)00087-9 [doi]
PST - ppublish
SO  - Biol Blood Marrow Transplant. 2003 May;9(5):292-303. doi: 
      10.1016/s1083-8791(03)00087-9.