AG-858

Under normal conditions, heat shock proteins are not found outside the cell. But if a cancerous or infected cell has become so sick that it dies and its membrane bursts, all of the cell’s contents spill out, including heat shock proteins that are bound to peptides. These extracellular HSPs send a very strong ‘dange r signal’ to the immune system, instructing it to destroy the other diseased cells. This is how it works:

* A sick cell dies and ruptures, spilling out the HSP-peptide complexes. * These extracellular complexes of HSPs and peptides are detected by circulating immune system cells called antigen-presenting cells (APCs). These APCs include cells called macrophages and dendritic cells. * The HSP complexes bind the CD91 receptor on the APC cell surface. The APC can then take in the HSP complexes. * Once the APCs have taken in the HSP complexes, they travel to the lymph nodes, which are clusters of immune system tissue that are distributed throughout the body. * In the lymph nodes, the APCs take the peptides that were associated with the HSPs and re-present them on the APC cell surface. These peptides are antigenic — meaning that they can stimulate an immune response. * In the lymph nodes, specialized immune cells called T cells ‘see’ these peptides and are then programmed to seek out cells bearing these specific, abnormal peptides. * Because every person and every cancer is different, the unique repertoire of antigenic peptides represents that individual patient’s specific cancer’s ‘fingerprint.’ The T cells are activated to target and destroy cancer cells bearing this fingerprint.