A novel monoclonal antibody raised to Daudi cell membranes was found to exhibit immune stimulatory and anti-tumor properties. The activity of this antibody (BAT) which also binds T cells was compared to that of anti-CD3. Anti-CD3 reacts with the T cell receptor complex, induces cell proliferation, and cytolytic activity in vitro and also manifests in vivo anti-tumor effect against murine tumors. Comparison of the two antibodies demonstrates similar induction in vitro of splenocyte proliferation and cytolytic activity. Both BAT and anti-CD3 antibodies manifest anti-tumor activity in mice bearing B16 melanoma. They differ however in the timing of antibody administration post-tumor inoculation which is most effective in eliciting the anti-tumor effect. Whereas BAT is most effective when administered 10 to 14 days post-tumor inoculation, anti-CD3 is effective at an early time. Data also indicate that BAT synergises with tumor cells in eliciting cell proliferation in vitro. In contrast, this effect could not be demonstrated with anti-CD3. The properties of BAT may be of advantage in its potential clinical use.
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Signal Transduct Target Ther
January 2025
Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Dynamic communication between hepatocytes and the environment is critical in hepatocellular carcinoma (HCC) development. Clinical immunotherapy against HCC is currently unsatisfactory and needs more systemic considerations, including the identification of new biomarkers and immune checkpoints. Transmembrane 4 L six family member 5 (TM4SF5) is known to promote HCC, but it remains unclear how cancerous hepatocytes avoid immune surveillance and whether avoidance can be blocked.
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January 2025
Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address:
Hematopoietic progenitor kinase 1 (HPK1), which negatively regulates immune signaling, has emerged as an attractive small-molecule drug target for tumor immunotherapy. Herein, we report the discovery of the 1,2,4-benzotriazine derivatives as new potent HPK1 inhibitors. Notably, compound A29 exhibited improved HPK1 inhibitory activity relative to compound 1 in the ADP-Glo kinase assay (IC = 2.
View Article and Find Full Text PDFImmunol Med
January 2025
Department of Rheumatology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.
Immune checkpoint molecules, including both co-inhibitory molecules and co-stimulatory molecules, are known to play critical roles in regulating T-cell responses. During the last decades, immunotherapies targeting these molecules (such as programmed cell death 1 (PD-1), and lymphocyte activation gene 3 (LAG-3)) have provided clinical benefits in many cancers. It is becoming apparent that not only T cells, but also B cells have a capacity to express some checkpoint molecules.
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January 2025
TriArm Therapeutics, Niudun Road 200, 201203 Shanghai, China. Electronic address:
Background: The immunosuppressive microenvironment negatively affects the efficacy of chimeric antigen receptor T (CAR-T) cells in solid tumors. Fusion protein that combining extracellular domain of inhibitory checkpoint protein and the cytoplasmic domain of stimulatory molecule may improve the efficacy of CAR-T cells by reversing the suppressive signals.
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Adv Mater
January 2025
Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, China.
Antigen-presenting cells (APCs) process tumor vaccines and present tumor antigens as the first signals to T cells to activate anti-tumor immunity, which process requires the assistance of co-stimulatory second signals on APCs. The immune checkpoint programmed death ligand 1 (PD-L1) not only mediates the immune escape of tumor cells but also acts as a co-inhibitory second signal on APCs. The serious dysfunction of second signals due to the high expression of PD-L1 on APCs in the tumor body results in the inefficiency of tumor vaccines.
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