PMID- 15507526
OWN - NLM
STAT- MEDLINE
DCOM- 20050303
LR  - 20220310
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 105
IP  - 4
DP  - 2005 Feb 15
TI  - Enhanced antilymphoma efficacy of CD19-redirected influenza MP1-specific CTLs by 
      cotransfer of T cells modified to present influenza MP1.
PG  - 1622-31
AB  - To enhance the in vivo antitumor activity of adoptively transferred, 
      CD19-specific chimeric antigen receptor (CAR)-redirected cytotoxic T lymphocytes 
      (CTLs), we studied the effect of restimulating CAR(+) CTLs through their 
      endogenous virus-specific T-cell antigen receptor (TcR) by the cotransfer of 
      engineered T-cell antigen-presenting cells (T-APCs). Using influenza A matrix 
      protein 1 (MP1) as a model antigen, we show that ex vivo-expanded CD4(+) and 
      CD8(+) T-APCs expressing a hygromycin phosphotransferase-MP1 fusion protein 
      (HyMP1) process and present MP1 to autologous human leukocyte antigen 
      (HLA)-restricted, MP1-specific CD4(+) and CD8(+) CTL precursors. The MP1-specific 
      CTLs are amenable to subsequent genetic modification to express a CD19-specific 
      CAR, designated CD19R, and acquire HLA-unrestricted reactivity toward CD19(+) 
      leukemia and lymphoma tumor targets while maintaining HLA-restricted MP1 
      specificity. The restimulation of MP1xCD19 dual-specific CTLs in vivo by the 
      adoptive transfer of irradiated HyMP1(+) T-APCs resulted in the enhanced 
      antilymphoma potency of bispecific effector cells, as measured by elimination of 
      the biophotonic signal of established firefly luciferase-expressing Burkitt 
      lymphoma xenografts in nonobese diabetic/severe combined immunodeficiency 
      (NOD/scid) animals compared with control groups restimulated by Hy(+)MP1(neg) 
      T-APCs. Engineered T-APCs are a novel and versatile antigen-delivery system for 
      generating antigen-specific T cells in vitro and enhancing the in vivo effector 
      functioning of CAR-redirected antitumor effector cells.
FAU - Cooper, Laurence J N
AU  - Cooper LJ
AD  - Beckman Research Institute, Division of Pediatric Hematology/Oncology, City of 
      Hope National Medical Center, Duarte, CA 91010-3000, USA. lcooper@coh.org
FAU - Al-Kadhimi, Zaid
AU  - Al-Kadhimi Z
FAU - Serrano, Lisa Marie
AU  - Serrano LM
FAU - Pfeiffer, Timothy
AU  - Pfeiffer T
FAU - Olivares, Simon
AU  - Olivares S
FAU - Castro, Adrian
AU  - Castro A
FAU - Chang, Wen-Chung
AU  - Chang WC
FAU - Gonzalez, Sergio
AU  - Gonzalez S
FAU - Smith, David
AU  - Smith D
FAU - Forman, Stephen J
AU  - Forman SJ
FAU - Jensen, Michael C
AU  - Jensen MC
LA  - eng
GR  - CA033572-21/CA/NCI NIH HHS/United States
GR  - CA30206-23/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041026
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD19)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (M1 protein, Influenza A virus)
RN  - 0 (Viral Matrix Proteins)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.119 (hygromycin-B kinase)
SB  - IM
MH  - Adoptive Transfer/methods
MH  - Animals
MH  - *Antigen Presentation/genetics
MH  - Antigen-Presenting Cells/immunology/metabolism/virology
MH  - Antigens, CD19/biosynthesis/*physiology
MH  - CD4-Positive T-Lymphocytes/immunology/virology
MH  - CD8-Positive T-Lymphocytes/immunology/virology
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - Coculture Techniques
MH  - Cytotoxicity Tests, Immunologic/methods
MH  - Epitopes, T-Lymphocyte/genetics/*immunology
MH  - Gene Transfer Techniques
MH  - Humans
MH  - Influenza A virus/genetics/immunology
MH  - K562 Cells
MH  - Lymphocyte Activation/genetics
MH  - Lymphoma/genetics/*immunology/*therapy/virology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Phosphotransferases (Alcohol Group Acceptor)/genetics
MH  - Plasmids
MH  - T-Lymphocytes/immunology/metabolism/*transplantation/virology
MH  - T-Lymphocytes, Cytotoxic/*immunology/metabolism/virology
MH  - Viral Matrix Proteins/biosynthesis/genetics/*immunology/metabolism
EDAT- 2004/10/28 09:00
MHDA- 2005/03/04 09:00
CRDT- 2004/10/28 09:00
PHST- 2004/10/28 09:00 [pubmed]
PHST- 2005/03/04 09:00 [medline]
PHST- 2004/10/28 09:00 [entrez]
AID - S0006-4971(20)45888-4 [pii]
AID - 10.1182/blood-2004-03-1208 [doi]
PST - ppublish
SO  - Blood. 2005 Feb 15;105(4):1622-31. doi: 10.1182/blood-2004-03-1208. Epub 2004 Oct 
      26.