Immunotherapy with autologous, human dendritic cells transfected with carcinoembryonic antigen mRNA.
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.
Morse
Michael A
MA
Department of Medicine, Medical Center, Box 3233, Durham, North Carolina 27710, USA. m.morse@cgct.duke.edu
Nair
Smita K
SK
Mosca
Paul J
PJ
Hobeika
Amy C
AC
Clay
Timothy M
TM
Deng
Yuping
Y
Boczkowski
David
D
Proia
Alan
A
Neidzwiecki
Donna
D
Clavien
Pierre-A
PA
Hurwitz
Herbert I
HI
Schlom
Jeffrey
J
Gilboa
Eli
E
Lyerly
H Kim
HK
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
D002272:Carcinoembryonic Antigen; D012333:RNA, Messenger; D011994:Recombinant Proteins