Alpha fetoprotein DNA prime and adenovirus boost immunization of two hepatocellular cancer patients.
BACKGROUND
Alpha fetoprotein (AFP) is an oncofetal antigen over-expressed by many hepatocellular cancers (HCC). We previously demonstrated that HLA-A2-restricted epitopes derived from AFP are immunogenic in vitro and in vivo despite high circulating levels of this oncofetal antigen. In order to test a more broadly applicable, HLA-unrestricted, inexpensive, cell-free vaccine platform capable of activating tumor antigen-specific CD8+ and CD4+ T cells, we tested full length AFP in a plasmid DNA construct in combination with an AFP-expressing replication-deficient adenovirus (AdV) in a prime-boost vaccine strategy.


METHODS
HCC patients who had an AFP+ tumor and previous treatment for HCC were screened and two patients received vaccination with three plasmid DNA injections followed by a single AdV injection, all delivered intramuscularly (i.m.).


RESULTS
The vaccine was well tolerated and safe. Both patients showed immunologic evidence of immunization. The first patient had a weak AFP-specific T cell response, a strong AdV-specific cellular response and recurred with an AFP-expressing HCC at nine months. The second patient developed a strong AFP-specific CD8+ and CD4+ cellular response and an AdV neutralizing antibody response, and recurred at 18 months without an increase in serum AFP.


CONCLUSIONS
The AFP DNA prime-AdV boost vaccine was safe and immunogenic. Circulating anti-AdV neutralizing antibodies at baseline did not prohibit the development of AFP-specific cellular immunity. The patient who developed CD8+ and CD4+ AFP-specific T cell immunity had more favorable progression-free survival. The observations with these two patients support development of this vaccine strategy in a larger clinical trial.


BACKGROUND
ClinicalTrials.gov: NCT00093548.
University of Pittsburgh Cancer Institute, Departments of Medicine, Surgery, and Immunology, University of Pittsburgh, 5117 Centre Avenue, PA, Pittsburgh 15213, USA. butterfieldl@upmc.edu.
Lisa H
LH
Butterfield
James S
JS
Economou
T Clark
TC
Gamblin
David A
DA
Geller
D000256:Adenoviridae / Q000276:immunology*; D000917:Antibody Formation; D019496:Cancer Vaccines / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006133:Growth Substances / Q000097:blood; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage*; D000509:alpha-Fetoproteins / Q000235:genetics*
D019496:Cancer Vaccines; D018925:Chemokines; D016207:Cytokines; D006133:Growth Substances; D019444:Vaccines, DNA; D000509:alpha-Fetoproteins