title: Engineered T cells for pancreatic cancer treatment.
abstract: OBJECTIVE
  Conventional chemotherapy and radiotherapy produce marginal survival benefits in pancreatic cancer, underscoring the need for novel therapies. The aim of this study is to develop an adoptive T cell transfer approach to target tumours expressing prostate stem cell antigen (PSCA), a tumour-associated antigen that is frequently expressed by pancreatic cancer cells.
  
  
  METHODS
  Expression of PSCA on cell lines and primary tumour samples was confirmed by immunohistochemistry. Healthy donor- and patient-derived T cells were isolated, activated in vitro using CD3/CD28, and transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) targeting PSCA. The ability of these cells to kill tumour cells was analysed by chromium-51 (Cr(51)) release.
  
  
  RESULTS
  Prostate stem cell antigen was expressed on >70% of the primary tumour samples screened. Activated, CAR-modified T cells could be readily generated in clinically relevant numbers and were specifically able to kill PSCA-expressing pancreatic cancer cell lines with no non-specific killing of PSCA-negative target cells, thus indicating the potential efficacy and safety of this approach.
  
  
  CONCLUSIONS
  Prostate stem cell antigen is frequently expressed on pancreatic cancer cells and can be targeted for immune-mediated destruction using CAR-modified, adoptively transferred T cells. The safety and efficacy of this approach indicate that it deserves further study and may represent a promising novel treatment for patients with pancreatic cancer.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Usha L
authors.initials: UL
authors.lastname: Katari
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Keirnan
authors.forename: Anna C
authors.initials: AC
authors.lastname: Worth
authors.forename: Sally E
authors.initials: SE
authors.lastname: Hodges
authors.forename: Ann M
authors.initials: AM
authors.lastname: Leen
authors.forename: William E
authors.initials: WE
authors.lastname: Fisher
authors.forename: Juan F
authors.initials: JF
authors.lastname: Vera
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005240:Feasibility Studies; D058851:GPI-Linked Proteins / Q000378:metabolism; D015316:Genetic Therapy; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D016853:Muromonab-CD3 / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics*; D057127:Single-Chain Antibodies / Q000096:biosynthesis / Q000235:genetics*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D013997:Time Factors; D014161:Transduction, Genetic; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D016853:Muromonab-CD3; D009363:Neoplasm Proteins; C110843:PSCA protein, human; D011948:Receptors, Antigen, T-Cell; D057127:Single-Chain Antibodies