RT Book, Section
A1 Lichtman, Marshall A.
A1 Kaushansky, Kenneth
A1 Prchal, Josef T.
A1 Levi, Marcel M.
A1 Burns, Linda J.
A1 Linch, David C.
SR Print(0)
ID 1189334335
T1 Immune Cell Therapy: Genetically Engineered T Cells
T2 Williams Manual of Hematology, 10e
YR 2022
FD 2022
PB McGraw-Hill Education
PP New York, NY
SN 9781264269204
LK hemonc.mhmedical.com/content.aspx?aid=1189334335
RD 2023/09/29
AB The  potent  antitumor  activity  of  T  cells  against  many  hematologic  malignancies  is  illustrated  by  the  graft-versus-leukemia  effect  of  both  allogeneic  hematopoietic  stem  cell  transplantation  and  donor  lymphocyte  infusion  (see  Chap.  39).Autologous  T  cells  recognizing  tumor  neoantigens  are  found  in  the  microenvironment  of  many  cancers.These  tumor-specific  T  cells  are  often  downregulated  by  the  expression  of  the  tumor  cells  of  a  range  of  immune  checkpoint  molecules.Attempts  to  expand  tumor-reactive  T  cells  in  vivo  using  interleukin  (IL)-2  infusions  have  met  with  some  success  in  selected  solid  cancers  such  as  melanoma  but  have  not  been  very  successful  in  the  hematologic  malignancies.Attempts  to  expand  in  vitro  and  subsequently  reinfuse  tumor-infiltrating  T  cells  (TILs)  has  had  considerable  success  in  melanoma  and  some  other  solid  tumors  but  is  logistically  highly  demanding.  Continued  trials  are  in  progress.The  use  of  ex  vivo  expanded  Epstein-Barr  virus  (EBV)-specific  T  cells  has  proven  efficacious  in  EBV-driven  lymphoproliferative  disorders.Infusion  of  bispecific  T-cell  engagers  (BiTEs)  and  trispecific  T-cell  engagers  (TriTEs)  enables  a  wide  range  of  previously  nonspecific  T  cells  to  be  recruited  to  tumor  cells,  leading  to  tumor  cell  death.  They  are  effective  in  a  number  of  hematologic  malignancies.An  alternative  strategy  to  recruit  a  wider  pool  of  autologous  T  cells  to  tumor  cell  killing  is  to  genetically  engineer  T  cells,  harvested  by  leukapheresis,  so  that  they  recognize  a  tumor-selective  antigen.  This  can  be  done  by  transfecting  these  cells  either  with  a  specific  T-cell  receptor  (TCR)  or  with  a  chimeric  antigen  receptor  (CAR).