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CD40 sits on the cells that teach T cells what to attack. Agonist antibodies press it to turn cold tumours hot; the strongest signals so far are in pancreatic cancer with chemotherapy.
CD40 (chromosome 20q13.12) is the receptor for CD40 ligand (TNFSF5/CD40LG) and transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells; it is expressed in B cells and in primary carcinomas (UniProt P25942). On activation, CD40 licenses dendritic cells to promote antitumour T-cell activation and re-educates macrophages to destroy tumour stroma; numerous agonist antibodies have been tolerable, with mild to moderate transient cytokine release, antitumour activity in melanoma, and major regressions in pancreatic cancer and mesothelioma with chemotherapy (Vonderheide 2020, Annu Rev Med). In the corpus, selicrelumab's intratumoural study ended with the end of drug development (NCT03892525) and mitazalimab is entering a phase 2/3 study with chemotherapy (NCT07437287).
In plain words · CD40 sits on the cells that teach T cells what to attack. Agonist antibodies press it to turn cold tumours hot; the strongest signals so far are in pancreatic cancer with chemotherapy.
CD40 sits on the cells that teach T cells what to attack. Agonist antibodies press it to turn cold tumours hot; the strongest signals so far are in pancreatic cancer with chemotherapy.
A TNF-receptor-superfamily member on antigen-presenting cells; the target of the CD40 agonist technology.
No product in this corpus aims at CD40 yet. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
First described 1989. Earliest sequence paper UniProt cites for the protein: Stamenkovic et al, EMBO J, 1989, "A B-lymphocyte activation molecule related to the nerve growth factor receptor and induced by cytokines in carcinomas". Source.
Sources: HGNC HGNC:11919 (approved symbol, name, aliases and cross-references); UniProt P25942 (protein name, function and tissue specificity)
A TNF-receptor-superfamily member on antigen-presenting cells; the target of the CD40 agonist technology.
Query for this target: (TITLE:"CD40" OR ABSTRACT:"CD40" OR TITLE:"TNFRSF5" OR ABSTRACT:"TNFRSF5" OR TITLE:"CD40 molecule" OR ABSTRACT:"CD40 molecule" OR TITLE:"Bp50" OR ABSTRACT:"Bp50" OR TITLE:"p50" OR ABSTRACT:"p50") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CD40, not a curated reading list.
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