Abstract
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. Posey and colleagues developed a CAR T cell therapy to break immune tolerance to solid tumors by targeting an aberrantly glycosylated, cancer-specific glycoprotein in multiple cancer histotypes and demonstrated efficacy and safety in tumors as diverse as leukemia and pancreatic cancer.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1444-1454 |
| Number of pages | 11 |
| Journal | Immunity |
| Volume | 44 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 21 2016 |
Fingerprint
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases
Cite this
Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma. / Posey, Avery D.; Schwab, Robert D.; Boesteanu, Alina C.; Steentoft, Catharina; Mandel, Ulla; Engels, Boris; Stone, Jennifer D.; Madsen, Thomas D.; Schreiber, Karin; Haines, Kathleen M.; Cogdill, Alexandria P.; Chen, Taylor J.; Song, Decheng; Scholler, John; Kranz, David M; Feldman, Michael D.; Young, Regina; Keith, Brian; Schreiber, Hans; Clausen, Henrik; Johnson, Laura A.; June, Carl H.
In: Immunity, Vol. 44, No. 6, 21.06.2016, p. 1444-1454.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma
AU - Posey, Avery D.
AU - Schwab, Robert D.
AU - Boesteanu, Alina C.
AU - Steentoft, Catharina
AU - Mandel, Ulla
AU - Engels, Boris
AU - Stone, Jennifer D.
AU - Madsen, Thomas D.
AU - Schreiber, Karin
AU - Haines, Kathleen M.
AU - Cogdill, Alexandria P.
AU - Chen, Taylor J.
AU - Song, Decheng
AU - Scholler, John
AU - Kranz, David M
AU - Feldman, Michael D.
AU - Young, Regina
AU - Keith, Brian
AU - Schreiber, Hans
AU - Clausen, Henrik
AU - Johnson, Laura A.
AU - June, Carl H.
PY - 2016/6/21
Y1 - 2016/6/21
N2 - 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. Posey and colleagues developed a CAR T cell therapy to break immune tolerance to solid tumors by targeting an aberrantly glycosylated, cancer-specific glycoprotein in multiple cancer histotypes and demonstrated efficacy and safety in tumors as diverse as leukemia and pancreatic cancer.
AB - 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. Posey and colleagues developed a CAR T cell therapy to break immune tolerance to solid tumors by targeting an aberrantly glycosylated, cancer-specific glycoprotein in multiple cancer histotypes and demonstrated efficacy and safety in tumors as diverse as leukemia and pancreatic cancer.
UR - http://www.scopus.com/inward/record.url?scp=84975028839&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84975028839&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2016.05.014
DO - 10.1016/j.immuni.2016.05.014
M3 - Article
VL - 44
SP - 1444
EP - 1454
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 6
ER -