title: Adoptive transfer of MART-1 T-cell receptor transgenic lymphocytes and dendritic cell vaccination in patients with metastatic melanoma.
abstract: OBJECTIVE
  It has been demonstrated that large numbers of tumor-specific T cells for adoptive cell transfer (ACT) can be manufactured by retroviral genetic engineering of autologous peripheral blood lymphocytes and expanding them over several weeks. In mouse models, this therapy is optimized when administered with dendritic cell (DC) vaccination. We developed a short 1-week manufacture protocol to determine the feasibility, safety, and antitumor efficacy of this double cell therapy.
  
  
  METHODS
  A clinical trial (NCT00910650) adoptively transferring MART-1 T-cell receptor (TCR) transgenic lymphocytes together with MART-1 peptide-pulsed DC vaccination in HLA-A2.1 patients with metastatic melanoma. Autologous TCR transgenic cells were manufactured in 6 to 7 days using retroviral vector gene transfer, and reinfused with (n = 10) or without (n = 3) prior cryopreservation.
  
  
  RESULTS
  A total of 14 patients with metastatic melanoma were enrolled and 9 of 13 treated patients (69%) showed evidence of tumor regression. Peripheral blood reconstitution with MART-1-specific T cells peaked within 2 weeks of ACT, indicating rapid in vivo expansion. Administration of freshly manufactured TCR transgenic T cells resulted in a higher persistence of MART-1-specific T cells in the blood as compared with cryopreserved. Evidence that DC vaccination could cause further in vivo expansion was only observed with ACT using noncryopreserved T cells.
  
  
  CONCLUSIONS
  Double cell therapy with ACT of TCR-engineered T cells with a very short ex vivo manipulation and DC vaccines is feasible and results in antitumor activity, but improvements are needed to maintain tumor responses.
authors.affiliation: Authors' Affiliations: Departments of Medicine, Surgery, Pathology and Laboratory Medicine, Microbiology, Immunology and Molecular Genetics, and Molecular and Medical Pharmacology; Jonsson Comprehensive Cancer Center; Department of Ophthalmology, Jules Stein Eye Institute; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research; Howard Hughes Medical Institute, University of California, Los Angeles (UCLA); The Angeles Clinic Research Institute, Los Angeles; Department of Medicine, University of California San Diego (UCSD) Moores Cancer Center, La Jolla; Divisions of Chemistry and Biology, California Institute of Technology, Pasadena, California; Department of Medical and Molecular Genetics, Indiana University, and the Indiana University Viral Production Facility (IU VPF), Indianapolis, Indiana; Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada; Mayo Clinic Scottsdale, Scottsdale, Arizona; Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut; and Center for Immunology, Roswell Park Cancer Institute, Buffalo, New York.
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authors.lastname: Kohn
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authors.forename: Owen N
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mesh_terms: D000328:Adult; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D058965:MART-1 Antigen / Q000235:genetics* / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D049268:Positron-Emission Tomography; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D014161:Transduction, Genetic; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D058965:MART-1 Antigen; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell