PMID- 14970938
OWN - NLM
STAT- MEDLINE
DCOM- 20040310
LR  - 20211203
IS  - 0093-7754 (Print)
IS  - 0093-7754 (Linking)
VI  - 31
IP  - 1
DP  - 2004 Feb
TI  - Immunoablative reduced-intensity stem cell transplantation: potential role of 
      donor Th2 and Tc2 cells.
PG  - 56-67
AB  - Allogeneic reduced-intensity stem cell transplantation (RISCT) decreases 
      regimen-associated morbidity and mortality, but it is unfortunately still 
      constrained by the same immune T-cell reactions that limit myeloablative 
      transplantation, including graft rejection, graft-versus-host disease (GVHD), and 
      suboptimal graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effects. Graft 
      rejection is mediated by host T cells, whereas GVHD and GVL/GVT effects are 
      initiated by donor T cells, and to this extent, future advances in RISCT will 
      likely benefit from an ability to modulate both donor and host T-cell immunity. 
      As a step in this direction, we have developed a RISCT approach that first 
      involves chemotherapy-induced host T-cell ablation, and second involves 
      administration of allogeneic inocula enriched for donor CD4(+) Th2 and CD8(+) Tc2 
      T-cell subsets that in murine studies mediate reduced GVHD. In a pilot clinical 
      trial, "immunoablative" RISCT with human leukocyte antigen (HLA)-matched related 
      allografts resulted in rapid and complete donor chimerism and GVL effects early 
      post-transplant, with GVHD being the primary toxicity. Using this immunoablative 
      RISCT approach, we are now evaluating the feasibility and safety of augmenting 
      allografts with additional donor CD4(+) Th2 cells that are generated in vitro via 
      CD3/CD28 costimulation in the presence of interleukin (IL)-4. We review the 
      biology of host and donor T-cell immunity during allogeneic RISCT and discuss the 
      strategies of host immunoablation and donor Th2 and Tc2 cell therapy as potential 
      means to improve the clinical results in RISCT.
FAU - Fowler, Daniel H
AU  - Fowler DH
AD  - National Institutes of Health, Center for Cancer Research, National Cancer 
      Institute, Bethesda, MD 20892, USA.
FAU - Bishop, Michael R
AU  - Bishop MR
FAU - Gress, Ronald E
AU  - Gress RE
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Semin Oncol
JT  - Seminars in oncology
JID - 0420432
SB  - IM
MH  - Animals
MH  - Cell Culture Techniques/methods
MH  - Graft vs Host Disease/immunology/prevention & control
MH  - Humans
MH  - Immunosuppression Therapy/methods
MH  - Mice
MH  - Stem Cell Transplantation/adverse effects/*methods
MH  - T-Lymphocytes, Cytotoxic/*transplantation
MH  - Th2 Cells/*transplantation
MH  - Transplantation Immunology
RF  - 100
EDAT- 2004/02/19 05:00
MHDA- 2004/03/11 05:00
CRDT- 2004/02/19 05:00
PHST- 2004/02/19 05:00 [pubmed]
PHST- 2004/03/11 05:00 [medline]
PHST- 2004/02/19 05:00 [entrez]
AID - S0093775403005657 [pii]
AID - 10.1053/j.seminoncol.2003.11.003 [doi]
PST - ppublish
SO  - Semin Oncol. 2004 Feb;31(1):56-67. doi: 10.1053/j.seminoncol.2003.11.003.