PMID- 20395199
OWN - NLM
STAT- MEDLINE
DCOM- 20100428
LR  - 20211020
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 70
IP  - 8
DP  - 2010 Apr 15
TI  - A high molecular weight melanoma-associated antigen-specific chimeric antigen 
      receptor redirects lymphocytes to target human melanomas.
PG  - 3027-33
LID - 10.1158/0008-5472.CAN-09-2824 [doi]
AB  - Immunotherapy, particularly the adoptive cell transfer (ACT) of 
      tumor-infiltrating lymphocytes (TIL), is a very promising therapy for metastatic 
      melanoma. Some patients unable to receive TIL have been successfully treated with 
      autologous peripheral blood lymphocytes (PBL), genetically modified to express 
      human leukocyte antigen (HLA) class I antigen-restricted, melanoma 
      antigen-reactive T-cell receptors; however, substantial numbers of patients 
      remain ineligible due to the lack of expression of the restricting HLA class I 
      allele. We sought to overcome this limitation by designing a non-MHC-restricted, 
      chimeric antigen receptor (CAR) targeting the high molecular weight 
      melanoma-associated antigen (HMW-MAA), which is highly expressed on more than 90% 
      of human melanomas but has a restricted distribution in normal tissues. 
      HMW-MAA-specific CARs containing an antigen recognition domain based on 
      variations of the HMW-MAA-specific monoclonal antibody 225.28S and a T-cell 
      activation domain based on combinations of CD28, 4-1BB, and CD3zeta activation 
      motifs were constructed within a retroviral vector to allow stable gene transfer 
      into cells and their progeny. Following optimization of the HMW-MAA-specific CAR 
      for expression and function in human PBL, these gene-modified T cells secreted 
      cytokines, were cytolytic, and proliferated in response to HMW-MAA-expressing 
      cell lines. Furthermore, the receptor functioned in both CD4(+) and CD8(+) cells, 
      was non-MHC restricted, and reacted against explanted human melanomas. To 
      evaluate this HMW-MAA-specific CAR in patients with metastatic melanoma, we 
      developed a clinical-grade retroviral packaging line. This may represent a novel 
      means to treat the majority of patients with advanced melanoma, most notably 
      those unable to receive current ACT therapies.
CI  - (c)2010 AACR.
FAU - Burns, William R
AU  - Burns WR
AD  - Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
FAU - Zhao, Yangbing
AU  - Zhao Y
FAU - Frankel, Timothy L
AU  - Frankel TL
FAU - Hinrichs, Christian S
AU  - Hinrichs CS
FAU - Zheng, Zhili
AU  - Zheng Z
FAU - Xu, Hui
AU  - Xu H
FAU - Feldman, Steven A
AU  - Feldman SA
FAU - Ferrone, Soldano
AU  - Ferrone S
FAU - Rosenberg, Steven A
AU  - Rosenberg SA
FAU - Morgan, Richard A
AU  - Morgan RA
LA  - eng
GR  - P01 CA109688/CA/NCI NIH HHS/United States
GR  - R01 CA110249/CA/NCI NIH HHS/United States
GR  - R01 CA138188/CA/NCI NIH HHS/United States
GR  - Z99 CA999999/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (HMW-MAA)
RN  - 0 (Receptors, Antigen)
SB  - IM
MH  - Alleles
MH  - Antigens, Neoplasm/*metabolism
MH  - CD4-Positive T-Lymphocytes/cytology
MH  - CD8-Positive T-Lymphocytes/cytology
MH  - Cell Line, Tumor
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Lymphocyte Activation
MH  - Lymphocytes/*metabolism
MH  - Lymphocytes, Tumor-Infiltrating/metabolism
MH  - Melanoma/immunology/*therapy
MH  - Receptors, Antigen/*chemistry
MH  - Retroviridae/genetics
MH  - Skin Neoplasms/immunology/*therapy
PMC - PMC3245576
MID - NIHMS182475
EDAT- 2010/04/17 06:00
MHDA- 2010/04/29 06:00
PMCR- 2011/12/23
CRDT- 2010/04/17 06:00
PHST- 2010/04/17 06:00 [entrez]
PHST- 2010/04/17 06:00 [pubmed]
PHST- 2010/04/29 06:00 [medline]
PHST- 2011/12/23 00:00 [pmc-release]
AID - 70/8/3027 [pii]
AID - 10.1158/0008-5472.CAN-09-2824 [doi]
PST - ppublish
SO  - Cancer Res. 2010 Apr 15;70(8):3027-33. doi: 10.1158/0008-5472.CAN-09-2824.