The research team led by professors Hong Han-soo and Park at the Gwangju Institute of Science and Technology (GIST) announced on the 14th that they have elucidated the interaction between the novel immunotherapeutic target CNTN4 and its interaction partner amyloid precursor protein (APP) in the immune synapse.
The joint research team developed an antibody GENA-104 that inhibits CNTN4, which could enhance the therapeutic efficacy of existing immunotherapies for cancer treatment.
Immunotherapies that activate the immune system by modulating interactions between immune checkpoint proteins are being actively researched to overcome resistance to conventional cancer treatments. The team found that CNTN4, a novel target, is overexpressed in various cancers such as gastric, liver, and pancreatic cancer, and binding of CNTN4 to T cells suppresses T cell proliferation and secretion of cytokines like interferon-gamma and tumor necrosis factor-alpha.
When T cells were co-cultured with GENA-104, an antibody that inhibits CNTN4 binding, the suppressed T cell proliferation and cytokine secretion were restored. GENA-104 neutralized the inhibitory effects of CNTN4 on T cell signaling and transcription factor nuclear translocation.
In animal models of cancer, treatment with GENA-104 resulted in significant tumor reduction, with a 75% tumor growth inhibition rate in CNTN4 overexpressing tumor models, indicating a proportional relationship between CNTN4 expression levels and tumor reduction rate.
The results suggest that GENA-104 effectively counters the T cell suppression mediated by CNTN4 and exhibits strong therapeutic potential in tumor models. The research team confirmed that CNTN4 interacts with APP on the surface of T cells to facilitate T cell suppression, and GENA-104 treatment increased cytotoxicity in APP WT T cells but not in APP KO T cells.
Professor Park Han-soo stated, “The research findings on the novel target CNTN4 have been recognized for their excellence by international experts in the field of immunology as they were published in reputable academic journals. The academic proof of the potential success of the CNTN4 inhibitory antibody GENA-104 is significant.”