title: Immunotherapy with autologous, human dendritic cells transfected with carcinoembryonic antigen mRNA.
abstract: Immunizations with dendritic cells (DC) transfected with RNA encoding tumor antigens induce potent tumor antigen-specific immune responses in vitro and in murine models. We performed a phase I study of patients with advanced carcinoembryonic antigen (CEA)-expressing malignancies followed by a phase II study of patients with resected hepatic metastases of colon cancer to assess safety and feasibility of administering autologous DC loaded with CEA mRNA. The immunizations were well tolerated. Of the 24 evaluable patients in the dose-escalation phase, there was 1 complete response (by tumor marker), 2 minor responses, 3 with stable disease, and 18 with progressive disease. In the phase II study, 9 of 13 patients have relapsed at a median of 122 days. Evidence of an immunologic response was demonstrated in biopsies of DC injection sites and peripheral blood of selected patients. We conclude that it is feasible and safe to administer mRNA-loaded DC to patients with advanced malignancies.
authors.affiliation: Department of Medicine, Medical Center, Box 3233, Durham, North Carolina 27710, USA. m.morse@cgct.duke.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
authors.forename: Smita K
authors.initials: SK
authors.lastname: Nair
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Mosca
authors.forename: Amy C
authors.initials: AC
authors.lastname: Hobeika
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Clay
authors.forename: Yuping
authors.initials: Y
authors.lastname: Deng
authors.forename: David
authors.initials: D
authors.lastname: Boczkowski
authors.forename: Alan
authors.initials: A
authors.lastname: Proia
authors.forename: Donna
authors.initials: D
authors.lastname: Neidzwiecki
authors.forename: Pierre-A
authors.initials: PA
authors.lastname: Clavien
authors.forename: Herbert I
authors.initials: HI
authors.lastname: Hurwitz
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: Eli
authors.initials: E
authors.lastname: Gilboa
authors.forename: H Kim
authors.initials: HK
authors.lastname: Lyerly
mesh_terms: D000328:Adult; D000368:Aged; D002272:Carcinoembryonic Antigen / Q000009:adverse effects / Q000235:genetics* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000473:pathology* / Q000628:therapy*; D003713:Dendritic Cells / Q000502:physiology / Q000637:transplantation*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007937:Leukapheresis; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D016019:Survival Analysis; D014162:Transfection / Q000379:methods; D014182:Transplantation, Autologous / Q000009:adverse effects / Q000401:mortality
chemical_list: D002272:Carcinoembryonic Antigen; D012333:RNA, Messenger; D011994:Recombinant Proteins