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

作者：Butterfield Lisa H^*; Economou James S; Gamblin T Clark; Geller David A

来源：Journal of Translational Medicine, 2014, 12(1): 86.

DOI：10.1186/1479-5876-12-86

• Alpha Fetoprotein
• Hepatocellular cancer
• Cancer vaccine
• Prime-boost

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. %26lt;br%26gt;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.). %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2014-4-5