The Journal of Immunology, 2007, 178: B194.
Copyright © 2007 by The American Association of Immunologists, Inc.
Vaccine for Cancer and Infectious Diseases
Albert B. Deisseroth,
Yucheng Tang,
Hakan Akbulut,
Jonathan Maynard and
Line Pedersen
Genetic Therapy, Sidney Kimmel Cancer Center, 10905 Road to the Cure, San Diego, 92121, United States Minor Outlying Islands
Abstract
In order to overcome defects in the immune response in older individuals, we have designed an adenoviral vector (Ad-sig-TAA/ecdCD40L) for the in vivo activation and tumor antigen loading of dendritic cells (DCs). This adenoviral vector encodes a fusion protein composed of an aminoterminal tumor associated antigen (TAA) fragment fused to the extracellular domain (ecd) of the CD40 ligand (CD40L) at the carboxyl terminal end. Two sc injections of this vector have broken tolerance to specific tumor associated antigens in two separate TAA.Tg transgenic mouse models (mice transgenic for rat Her-2-Neu (rH2N) and human MUC-1 (hMUC-1)). The immunoprotection extends for over a year and is independent of CD4 cells. We showed that the sc injection of the hMUC-1/ecdCD40L protein following the sc injection of the Ad-sig-TAA/ecdCD40L vector (this vector prime-protein boost is called VPP) increases the levels of both the cellular and humoral immune response over that achievable with just the vector injections alone in the hMUC-1.Tg mice. The antibodies from hMUC-1 VPP vaccinated mice bind to biopsy specimens of human cancers of the breast and prostate. Importantly, the VPP vaccination can induce an immune response even in 18 month old mice which completely suppresses tumor growth in old (18 month old) mice. The Ad-sig-rH2N/ecdCD40L vaccination suppresses the evolution of spontaneous breast cancer in the rH2N.Tg mouse model. The Ad-sig-HA/ecdCD40L vector prime-HA/ecdCD40L protein boost which is directed to the H5N1 avian influenza hemagglutinin (HA) antigen induces neutralizing antibodies against the H5N1 486 avian influenza virus at 1/4000 dilution of the serum.
