Chronic lymphocytic leukemia (CLL) is an ideal disease for therapeutic vaccine strategies. While the leukemia cells are usually stealth-like, avoiding T cell recognition, they can be manipulated through ligation of CD40 on their surface to become very effective antigen presenting cells (APCs). Ligation of CD40 leads to expression of CD80, CD86 and upregulation of CD54. Other biochemical changes occur upon ligation of CD40, including upregulation of CD95, DR5, and expression of Bid, predisposing the leukemia cells to death-receptor-induced apoptosis. CLL cells can be made to express CD154 (CD40-ligand) using a replication-defective adenovirus. A phase I clinical trial with autologous CLL cells transduced to express murine CD154 previously demonstrated tolerability and clinical activity with this strategy (
Disclosure:Research Funding: Bayer Healthcare, sanofi-aventis, MemGen, Genitope, Genmab, Sunesis, Abbott Laboratories. Honoraria Information: Celgene.