论文部分内容阅读
Our laboratory has created the Ad-sig-TAA/ecdCD40L vector prime-TAA/ecdCD40L protein boost vaccine strategy (we call this the TAA/ecdCD40L VPPP vaccine) to overcome the diminished immune response seen in cancer, chronic viral infections and advanced age.Attaching the target associated antigens (TAA) to the CD40L activates dendritic cells (DCs) and delivers TAA to the inside of the DCs where it becomes presented on Class Ⅰ MHC.The use of the adenovirus to deliver the TAA/ecdCD40L transcription unit activates the innate immune response through binding of viral DNA to Toll-like receptor 9 on DCs.This expands the magnitude of the adaptive immune response induced by the vaccine.The use of the TAA/ecdCD40L protein boost to the Ad-sig-TAA/ecdCD40L vector further increases the levels of the TAA specific CD8 effector T cells and antibodies over that which is possible with the Ad-sigTAA/ecdCD40L vector alone.We have shown that the TAA/ecdCD40L VPPP vaccine can overcome the anergy to TAA present in TAA.Tg mice {where TAA was either the rat Her-2-Neu (rH2N) or human Mucin-1(hMUC-1)} even when these test mice are of an advanced chronological age (18 months).The induction of an immune response with the TAA/ecdCD40L VPP vaccine does not require the presence of CD4 T cells.We have tested this platform successfully with the following TAA: the rH2N and hMUC-1 TAA which are associated with breast cancer, p210Bcr-Abl of chronic myelogenous leukemia (CML), the melanoma associated antigen: tyrosinase related protein-2, HPV E7, and influenza antigens M2 and HA.The Ad-sig-rH2N/ecdCD40L vector prime-rH2N/ecdCD40L vaccine administered to rH2N.Tg mice starting at 6 weeks of age reduced the incidence of mammary cancer at 6 months by 50%.Finally, this vaccine works even in patients rendered lymphopenic by myeloablative therapy.