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

Butterfield, LH and Economou, JS and Gamblin, TC and Geller, DA (2014) Alpha fetoprotein DNA prime and adenovirus boost immunization of two hepatocellular cancer patients. Journal of Translational Medicine, 12 (1).

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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. © 2014 Butterfield et al.; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Butterfield, LHlhb3@pitt.eduLHB3
Economou, JS
Gamblin, TC
Geller, DAdageller@pitt.eduDAGELLER
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 5 April 2014
Date Type: Publication
Journal or Publication Title: Journal of Translational Medicine
Volume: 12
Number: 1
DOI or Unique Handle: 10.1186/1479-5876-12-86
Schools and Programs: School of Medicine > Immunology
School of Medicine > Medicine
School of Medicine > Surgery
Refereed: Yes
Date Deposited: 05 Dec 2016 21:16
Last Modified: 04 Feb 2019 15:58
URI: http://d-scholarship.pitt.edu/id/eprint/29576

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