Because it has been shown that agonistic anti-4-1BB antibody treatment does not induce inflammatory responses in endothelial cells when 4-1BB expression is low , we thought that 4-1BB expression on muscle cells might not be strong enough in the noninflamed condition to lead to stimulation by the agonistic antibody
. In agreement with this view, pretreatment with TNF[alpha] markedly upregulated 4-1BB expression, and subsequent treatment with agonistic antibody
enhanced inflammatory cytokine production (TNF[alpha], IL-6, and MCP-1) in muscle cells from WT mice; moreover, these changes were completely abrogated in 4-1BB-deficient muscle cells, confirming the need for 4-1BB stimulation.
The company's lead product candidate, CTX-471, is a fully human agonistic antibody
of CD137, which is in a Phase 1 study in patients with inadequate responses to PD-1/PD-L1 checkpoint inhibitors.