title: Redirected T cells that target pancreatic adenocarcinoma antigens eliminate tumors and metastases in mice.
abstract: OBJECTIVE
  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 × 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/neu-specific 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.
authors: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel; Gastroenterology and Liver Diseases Institute, Assaf Harofeh Medical Center, Zriffin, Israel.
authors: Amit
authors: A
authors: Maliar
authors: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors: Charlotte
authors: C
authors: Servais
authors: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors: Tova
authors: T
authors: Waks
authors: Center for Molecular Medicine Cologne and Tumor Genetics, Department I Internal Medicine, Köln, Germany.
authors: Markus
authors: M
authors: Chmielewski
authors: Department of Surgery B, Assaf Harofeh Medical Center, Zriffin, Israel.
authors: Ron
authors: R
authors: Lavy
authors: Tumor Immunology, German Cancer Research Center, Heidelberg, Germany.
authors: Peter
authors: P
authors: Altevogt
authors: Center for Molecular Medicine Cologne and Tumor Genetics, Department I Internal Medicine, Köln, Germany.
authors: Hinrich
authors: H
authors: Abken
authors: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel. Electronic address: zelig.eshhar@weizmann.ac.il.
authors: Zelig
authors: Z
authors: Eshhar
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D000818:Animals; D051927:CD24 Antigen / Q000276:immunology; D045744:Cell Line, Tumor; D006801:Humans; D016219:Immunotherapy, Adoptive; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000378:metabolism / Q000637:transplantation*
chemical_list: D051927:CD24 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases