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Journal of Translational Medicine

, 12:86

Cell, tissue and gene therapy

Abstract

BackgroundAlpha 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.

MethodsHCC 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



ResultsThe 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.

ConclusionsThe 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 registrationClinicalTrials.gov: NCT00093548

KeywordsAlpha Fetoprotein Hepatocellular cancer Cancer vaccine Prime-boost AbbreviationsAFPAlpha fetoprotein

HCCHepatocellular cancer

AdVAdenovirus

USUnited States

PBMCPeripheral blood mononuclear cells

HBVHepatitis B virus

HCVHepatitis C virus

RFARadiofrequency ablation

TAETransarterial embolization

LLDLower limit of detection

GMPGood manufacturing practice

IMIntramuscular.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-12-86 contains supplementary material, which is available to authorized users.

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Autor: Lisa H Butterfield - James S Economou - T Clark Gamblin - David A Geller

Fuente: https://link.springer.com/







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