Anti-Human TWEAK receptor Recombinant Antibody (TAB-178) (CAT#: TAB-178)

Vredevoogd, David W., et al. "Augmenting immunotherapy impact by lowering tumor TNF cytotoxicity threshold." Cell 178.3 (2019): 585-599. https://doi.org/10.1016/j.cell.2019.06.014

This research addresses a significant challenge in cancer immunotherapy by exploring how tumors with low levels of tumor necrosis factor (TNF) can be sensitized to T cell-mediated killing. Through a genome-wide CRISPR/Cas9 screen, the study identified TNF receptor-associated factor 2 (TRAF2) as a critical gatekeeper that regulates tumor sensitivity to T cell-derived TNF. The researchers demonstrated that TRAF2 inactivation dramatically lowers the tumor cytotoxicity threshold to physiologically relevant low TNF concentrations by redirecting TNF signaling toward RIPK1-dependent apoptosis. Clinical data analysis revealed that TNF abundance is generally low in untreated tumors and in non-responders to immune checkpoint blockade (ICB), but rises in responding patients, suggesting that targeting the TNF pathway could enhance ICB efficacy.
Creative Biolabs provided the agonistic anti-Fn14 antibody (TAB-178) used in this study, which was critical for demonstrating that clustering of Fn14 receptors could sensitize tumor cells to T cell-derived TNF by downregulating TRAF2. This antibody helped the researchers establish that targeted degradation of TRAF2 via the Fn14-TWEAK pathway represents a promising approach for translating their findings toward clinical applications. The combination of TRAF2 targeting (via Fn14 agonism) with cIAP1/2 inhibition demonstrated synergistic enhancement of tumor cell sensitivity to T cell attack, providing a potential new strategy to overcome intrinsic resistance to immunotherapy.