Self‐polymerizing Zfra peptides elicit immune response for targeting cancer

Abstract

A novel immune response in targeting skin, breast, and many other cancer cells can be elicited by using self‐polymerizing peptides. Synthetic Zfra, a 31‐amino‐acid zinc finger‐like protein that regulates apoptosis, undergoes self‐polymerization in degassed enzyme‐free solutions. Pre‐injection of the full length Zfra1‐31, or truncated Zfra4‐10, via tail veins (<40 micromoles) protects nude mice from growing human lung cancer NCI‐H1299, basal cell carcinoma BCC, melanoma B16F10, glioma 13‐06‐MG and U87‐ MG, and many others. Alteration of Ser8 to Gly resulted in failure of self‐polymerization and cancer suppression, suggesting that Ser8 is central to the function of Zfra both in vivo and in vitro. When spleen cells from Zfra‐treated nude mice were transferred to naïve nude mice, these mice became resistant to the growth of implanted cancer cells (50–78% suppression), suggesting that non‐ T “memory” cells are involved in blocking cancer growth. NODSCID mice, which are defective in innate T and B cells, failed to generate anticancer response upon pretreatment with Zfra peptides. The observations suggest non‐T immune cells are involved in anticancer response. (supported by DoD, USA and NHRI and NSC, Taiwan)