Maliar, Amit, Servais, Charlotte, Waks, Tova, Chmielewski, Markus, Lavy, Ron, Altevogt, Peter, Abken, Hinrich and Eshhar, Zelig (2012). Redirected T Cells That Target Pancreatic Adenocarcinoma Antigens Eliminate Tumors and Metastases in Mice. Gastroenterology, 143 (5). S. 1375 - 1390. PHILADELPHIA: W B SAUNDERS CO-ELSEVIER INC. ISSN 1528-0012
Full text not available from this repository.Abstract
BACKGROUND & AIMS: Pancreatic adenocarcinoma (PAC) is often diagnosed at an advanced and inoperable stage, and standard systemic treatments are generally ineffective. We investigated the effects of adoptive transfer of tumor-specific T cells that express chimeric antibody-based receptors (CAR) to mice with primary and metastatic PAC xenografts. METHODS: Human effector T cells were genetically modified to express CAR against Her2/neu or CD24, a putative PAC stem cell antigen. The antitumor reactivity of the engineered T cells (T-bodies) was evaluated in SCID mice with different PAC xenografts. A total of 1 x 10(7) T-bodies were injected via the tail vein or directly administered to the subcutaneous tumor on 3 or 4 alternating days. Mice were then given twice-daily intraperitoneal injections of interleukin-2 for 10 days. RESULTS: Intratumor injection of human CD24 and Her2/neu-specific T-bodies completely eliminated the tumors from most animals. Intravenous injection of T-bodies reduced tumor size and prolonged survival of mice with orthotopically transplanted tumors; more than 50% of animals appeared to be disease-free more than 2 months later. Additional systemic administration of T-bodies 8 weeks after the initial injection eliminated primary tumors, along with liver and draining lymph node metastases. A single administration of the Her2/neuspecific T-bodies prolonged the survival of mice with tumors in which most of the cells expressed the target antigen. In contrast, the CD24-specific T-bodies prolonged survival of mice in which only a subpopulation of the tumor cells expressed the antigen. CONCLUSIONS: CAR-redirected T cells stop growth and metastasis of PAC xenografts in mice. T-bodies specific to CD24, a putative cancer stem cell antigen, were effective against PAC xenografts that had only a subset of antigen-expressing cells.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||
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| URN: | urn:nbn:de:hbz:38-479858 | ||||||||||||||||||||||||||||||||||||
| DOI: | 10.1053/j.gastro.2012.07.017 | ||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Gastroenterology | ||||||||||||||||||||||||||||||||||||
| Volume: | 143 | ||||||||||||||||||||||||||||||||||||
| Number: | 5 | ||||||||||||||||||||||||||||||||||||
| Page Range: | S. 1375 - 1390 | ||||||||||||||||||||||||||||||||||||
| Date: | 2012 | ||||||||||||||||||||||||||||||||||||
| Publisher: | W B SAUNDERS CO-ELSEVIER INC | ||||||||||||||||||||||||||||||||||||
| Place of Publication: | PHILADELPHIA | ||||||||||||||||||||||||||||||||||||
| ISSN: | 1528-0012 | ||||||||||||||||||||||||||||||||||||
| Language: | English | ||||||||||||||||||||||||||||||||||||
| Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||
| Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||
| Subjects: | no entry | ||||||||||||||||||||||||||||||||||||
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| URI: | http://kups.ub.uni-koeln.de/id/eprint/47985 |
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