PMID- 24329799
OWN - NLM
STAT- MEDLINE
DCOM- 20140731
LR  - 20211203
IS  - 1600-065X (Electronic)
IS  - 0105-2896 (Print)
IS  - 0105-2896 (Linking)
VI  - 257
IP  - 1
DP  - 2014 Jan
TI  - Rapamycin-resistant effector T-cell therapy.
PG  - 210-25
LID - 10.1111/imr.12127 [doi]
AB  - Pharmacologic inhibition of the mechanistic target of rapamycin (mTOR) represents 
      a stress test for tumor cells and T cells. Mechanisms exist that allow cells to 
      survive this stress, including suboptimal target block, alternative signaling 
      pathways, and autophagy. Rapamycin-resistant effector T (T-Rapa) cells have an 
      altered phenotype that associates with increased function. Ex vivo rapamycin, 
      when used in combination with polarizing cytokines and antigen-presenting-cell 
      free costimulation, is a flexible therapeutic approach as polarization to 
      T-helper 1 (Th1)- or Th2-type effectors is possible. Murine T-Rapa cells skewed 
      toward a Th2-type prevented graft rejection and graft-versus-host disease (GVHD) 
      more potently than control Th2 cells and effectively balanced GVHD and 
      graft-versus-tumor (GVT) effects. A phase II clinical trial using low-intensity 
      allogeneic hematopoietic cell transplantation demonstrated that interleukin-4 
      polarized human T-Rapa cells had a mixed Th2/Th1 phenotype; T-Rapa cell 
      recipients had a balanced Th2/Th1 cytokine profile, conversion of mixed chimerism 
      toward full donor chimerism, and a potentially favorable balance between GVHD and 
      GVT effects. In addition, a phase I clinical trial evaluating autologous T-Rapa 
      cells skewed toward a Th1- and Tc1-type is underway. Use of ex vivo rapamycin to 
      modulate effector T-cell function represents a promising new approach to 
      transplantation therapy.
CI  - Published 2013. This article is a U.S. Government work and is in the public 
      domain in the USA.
FAU - Fowler, Daniel H
AU  - Fowler DH
AD  - Experimental Transplantation and Immunology Branch, National Cancer Institute, 
      Center for Cancer Research, Bethesda, MD, USA.
LA  - eng
GR  - Z01 SC010288/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Review
PL  - England
TA  - Immunol Rev
JT  - Immunological reviews
JID - 7702118
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - *Cell- and Tissue-Based Therapy/methods
MH  - Clinical Trials as Topic
MH  - *Drug Resistance
MH  - Graft vs Host Disease/etiology/prevention & control
MH  - Hematopoietic Stem Cell Transplantation/adverse effects
MH  - Humans
MH  - Neoplasms/immunology/therapy
MH  - Sirolimus/*pharmacology
MH  - T-Lymphocyte Subsets/*drug effects/*immunology/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Th1 Cells/drug effects/immunology/metabolism
MH  - Th2 Cells/drug effects/immunology/metabolism
MH  - Transplantation, Homologous
PMC - PMC6948844
MID - NIHMS1064827
OTO - NOTNLM
OT  - Th1/Th2/Th17
OT  - apoptosis/autophagy
OT  - cytokines
OT  - graft versus host disease
OT  - transplantation
EDAT- 2013/12/18 06:00
MHDA- 2014/08/01 06:00
PMCR- 2020/01/08
CRDT- 2013/12/17 06:00
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/08/01 06:00 [medline]
PHST- 2020/01/08 00:00 [pmc-release]
AID - 10.1111/imr.12127 [doi]
PST - ppublish
SO  - Immunol Rev. 2014 Jan;257(1):210-25. doi: 10.1111/imr.12127.