HERA-CD27L: A Potent Hexavalent Agonist for Cancer Immunotherapy and Memory T Cell Enhancement in Mouse Models

The abstract discusses the development of a unique technology platform by Apogenix for the creation of hexavalent TNFRSF agonists, known as HERA, which are utilized in cancer treatment. These proteins are designed to mimic TNFSF cytokines and are structured around a trivalent single-chain TNFSF receptor-binding domain (scTNFSF-RBD) that is deficient in Fc-γ receptor (FcγR) binding. This design allows HERA proteins to cluster six receptors effectively.

The HERA platform has been applied to various agonists, including CD27L, which is a significant co-stimulatory molecule that promotes T cell activation and survival by interacting with its receptor, CD27. HERA-CD27L is produced in CHO suspension cells and purified to ensure homogeneity and absence of aggregates. It has been shown to bind its target receptor with high affinity and to enhance T cell expansion in vitro.

In vivo studies have demonstrated that HERA-CD27L can increase the clonal expansion of antigen-specific CD8+ T cells, leading to significant tumor growth inhibition in mouse models of colorectal cancer. The treatment also appears to enhance memory formation in both CD4+ and CD8+ T cells.

The research concludes that the hexavalent HERA-CD27L agonist exhibits potent immune cell-driven anti-tumor efficacy, suggesting its potential use in cancer treatment either as a standalone agent or in combination with checkpoint inhibitors. The study was presented at the American Association for Cancer Research Annual Meeting in 2017.