Knowledge Sharing

c-MET, a receptor tyrosine kinase encoded by the MET proto-oncogene, is activated by HGF. It regulates cell proliferation, migration and tissue repair under normal conditions. Aberrant activation from mutations, amplification or exon 14 skipping drives tumor progression, metastasis and resistance to EGFR-targeted therapies.

TSLP is a pleiotropic cytokine mainly secreted by epithelial cells, fibroblasts and mast cells. It acts on dendritic, T and B cells to promote activation, differentiation and proliferation, induce Th2 cytokines, and activate JAK-STAT signaling. TSLP drives Th2 immune responses and is critical in immune regulation, inflammation and disease progression.

CD5 is a key scavenger receptor family transmembrane glycoprotein that negatively regulates TCR/BCR signaling to maintain immune tolerance. It promotes tumor cell survival via NF-κB and PI3K/Akt pathways. Predominantly expressed on T cells and some immune subsets but absent in normal stem cells and solid tissues, CD5 enables highly specific targeted therapy with minimal off-target effects.

PD-1 is a key immunosuppressive receptor on immune cells that inhibits activation via PD-L1/PD-L2. It prevents autoimmunity under normal conditions but mediates tumor immune escape when hijacked by cancer cells. Abnormal PD-1 signaling also contributes to autoimmune diseases by suppressing immune clearance of abnormal self-cells.

GPCRs are key membrane signal-transduction proteins regulating diverse physiological functions. AT1R is critical for blood pressure and cardiovascular health. The activation mechanism of peptide-binding GPCRs like AT1R has long been a bottleneck. Using synthetic nanobodies, researchers resolved this issue, with results published in Cell, advancing GPCR research and drug development.

CD7 is a transmembrane glycoprotein mainly expressed on T cells, NK cells and their precursors. It is highly upregulated in hematologic malignancies including T-ALL and lymphomas. As an immunoglobulin superfamily member, CD7 mediates T-cell activation, adhesion and signaling, and serves as a key marker for T-cell malignancies. Its specific and stable expression makes it an ideal target for novel immunotherapies.

CD8 is a membrane‑bound glycoprotein expressed on cytotoxic T cells, subsets of NK cells and developing thymocytes. As an αβ heterodimer TCR co‑receptor, it binds MHC‑I to strengthen TCR affinity and promote T‑cell activation. Essential for antiviral and antitumor immunity, CD8 serves as a key target in tumor immunotherapy and immune regulation research.

CD8 is a membrane glycoprotein expressed on cytotoxic T cells, some NK cells and developing thymocytes. It acts as a TCR co-receptor, mostly as an αβ heterodimer, binding MHC-I to boost TCR-peptide-MHC affinity, enhance signaling and T-cell activation. Critical for antiviral and antitumor immunity, CD8 is a key target in tumor immunotherapy and immune mechanism studies.

2024 data from China’s National Health Commission shows Chinese adult overweight and obesity rates at 34.3% and 16.4%, meaning over half are overweight. Obesity raises risks of diabetes, cardiovascular diseases, cancers and metabolic syndrome. By 2050, over half of adults worldwide may be affected. Given limited lifestyle intervention efficacy and drug side effects, safe and effective novel anti-obesity strategies are urgently needed.

Psoriatic arthritis (PsA) is a chronic inflammatory disease impairing skin, joints and entheses, severely reducing patients’ quality of life. Conventional DMARDs and monoclonal antibodies show limited efficacy, poor tissue penetration and low synovial drug levels. IL‑17A and IL‑17F jointly drive PsA inflammation, so single‑cytokine inhibition is inadequate. Novel dual‑targeting antibodies with improved tissue penetration are urgently needed to overcome these therapeutic bottlenecks.

T-cell malignancies are aggressive hematologic tumors with high relapse and poor prognosis. CD5, a key marker of malignant T-cells, is also present on normal T-cells, so CD5-targeted CAR-T cannot distinguish tumor from normal cells, causing T-cell depletion and immune deficiency. NK cells are ideal effectors as they kill tumors without prior sensitization and do not express CD5, enabling safe targeting of CD5+ malignant T-cells.

Immune checkpoint inhibitors have revolutionized human cancer therapy, driving demand for comparable treatments in dogs. Canine spontaneous tumors resemble human cancers, making them excellent translational models. Yet specific anti-canine PD-L1 immunotherapies remain scarce. Current antibodies suffer from immunogenicity and high costs. Nanobody-based inhibitors could benefit veterinary oncology and inform human immunotherapy.