Alpha fetoprotein DNA prime and adenovirus boost immunization of two hepatocellular cancer patients.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov: NCT00093548.

• Authors: Lisa H Butterfield, James S Economou, T Clark Gamblin, David A Geller
• Journal: Journal of translational medicine (J Transl Med) Vol. 12 Pg. 86 (Apr 05 2014) ISSN: 1479-5876 [Electronic] England
• PMID: 24708667 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Chemokines
• Cytokines
• Growth Substances
• Vaccines, DNA
• alpha-Fetoproteins

Topics

• Adenoviridae (immunology)
• Antibody Formation
• Cancer Vaccines (administration & dosage)
• Carcinoma, Hepatocellular (immunology)
• Chemokines (blood)
• Cytokines (blood)
• Enzyme-Linked Immunosorbent Assay
• Growth Substances (blood)
• Humans
• Liver Neoplasms (immunology)
• Vaccines, DNA (administration & dosage)
• alpha-Fetoproteins (genetics)