The CD40 agonist HERA-CD40L results in enhanced activation of antigen presenting cells, promoting an anti-tumor effect alone and in combination with radiotherapy.

Introduction: The ability to modulate and enhance the anti-tumor immune responses is critical in developing novel therapies in cancer. The Tumor Necrosis Factor (TNF) Receptor Super Family (TNFRSF) are potentially excellent targets for modulation which result in specific anti-tumor immune responses. CD40 is a member of the TNFRSF and several clinical therapies are under development.

CD95L and Anti-Tumor Immune Response: Current Understanding and New Evidence.

The ability of FasL/CD95L to induce apoptosis in various Fas/CD95-expressing cells has been described in the context of hematopoiesis or thymic elimination of self-reactive T cells and resolution of an acute immune response under physiological conditions. At the same time, non-apoptotic CD95 activation is widely described in cancer and shown to stimulate invasiveness of cancer cells, promote cancer progression as well as stemness of cancer cells. This paper puts emphasis on the evolving understanding of expression and the non-apoptotic activities of the CD95/CD95L signaling pathway on the function of tumor cells, tumor microenvironment and immune cells.

Correction: CD95 maintains stem cell-like and non-classical EMT programs in primary human glioblastoma cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Asunercept as an innovative therapeutic approach for recurrent glioblastoma and other malignancies.

Glioblastoma is the most common and aggressive malignant tumor of the central nervous system. Despite the existing high unmet medical needs, the past few decades have seen no notable improvement in overall survival for glioblastoma patients. One active area of research to develop new therapeutic options for this disease is focusing on the CD95/Fas receptor and its ligand CD95L/FasL.

Concepts for agonistic targeting of CD40 in immuno-oncology.

TNF Receptor Superfamily (TNF-R-SF) signaling is a structurally well-defined event that requires proper receptor clustering and trimerization. While the TNF-SF ligands naturally exist as trivalent functional units, the receptors are usually separated on the cell surface. Critically, receptor assembly into functional trimeric signaling complexes occurs through binding of the natural ligand unit.