Grant: CIHR/Regional Partnership Program/Operating Grants

Acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus type-1 (HIV-1)-infected patients is a rapidly expanding global pandemic, which causes millions of individuals died each year. Highly active antiviral therapy (HAART) is currently the only means to halt progression of AIDS. Although HAART which suppresses viral replication has significantly improved prognosis, it is unable to eliminate the proviral latent reservoir leading to some residual viruses remaining in treated AIDS patients. CD4+ T cells are required for generation and maintenance of cytotoxic CD8+ T cells playing a critical role in control of HIV-1 proliferation. However, CD4+ T cell depletion usually occurs in AIDS patients due to the viral cytopathic effect derived from binding of trimeric gp120 to CD4 of T cells. Therefore, how to stimulate efficient CD8+ CTL responses in AIDS patients becomes one of the major challenges in AIDS patient therapy. Since early HIV-1 proteins such as tat can broadern and enhance CD8+ CTL responses against late HIV-1 proteins such as gp120 and gag, a combined early and late HIV-1 protein-specific EXO-targeted T (aTexo) cells may be used as a novel immunotherapeutic vaccine capable of overcoming CD4+ T cell deficiency, dendritic cell (DC) dysfunction and immune suppression, and stimulating effective gp120-/gag-specific CD8+ CTL responses in AIDS patients with immune suppression and declined CD4+ T cells.