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Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the
Membrane Mucin MUC1 Control Adenocarcinoma
#MMPMID27332733
Posey AD Jr
; Schwab RD
; Boesteanu AC
; Steentoft C
; Mandel U
; Engels B
; Stone JD
; Madsen TD
; Schreiber K
; Haines KM
; Cogdill AP
; Chen TJ
; Song D
; Scholler J
; Kranz DM
; Feldman MD
; Young R
; Keith B
; Schreiber H
; Clausen H
; Johnson LA
; June CH
Immunity
2016[Jun]; 44
(6
): 1444-54
PMID27332733
show ga
Genetically modified T cells expressing chimeric antigen receptors (CARs)
demonstrate robust responses against lineage restricted, non-essential targets in
hematologic cancers. However, in solid tumors, the full potential of CAR T cell
therapy is limited by the availability of cell surface antigens with sufficient
cancer-specific expression. The majority of CAR targets have been normal
self-antigens on dispensable hematopoietic tissues or overexpressed shared
antigens. Here, we established that abnormal self-antigens can serve as targets
for tumor rejection. We developed a CAR that recognized cancer-associated Tn
glycoform of MUC1, a neoantigen expressed in a variety of cancers. Anti-Tn-MUC1
CAR T cells demonstrated target-specific cytotoxicity and successfully controlled
tumor growth in xenograft models of T cell leukemia and pancreatic cancer. These
findings demonstrate the therapeutic efficacy of CAR T cells directed against
Tn-MUC1 and present aberrantly glycosylated antigens as a novel class of targets
for tumor therapy with engineered T cells.
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