Related Experiment Video
Updated: Sep 18, 2025
07:04
Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
Published on: May 2, 2025
551
Negative Immune Checkpoint Inhibitors
Magda Drewniak-Świtalska1, Paulina Fortuna2, Małgorzata Krzystek-Korpacka1
1Department of Biochemistry and Immunochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland.
Pharmaceutics
|June 27, 2025
Summary
Small-molecule and peptide checkpoint inhibitors offer advantages over antibodies for cancer therapy. New PROTACs degrade immune-suppressing proteins, enhancing T-lymphocyte activation against cancer.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Checkpoint inhibitors unlock the immune system to fight cancer, metabolic diseases, and infections by activating T lymphocytes.
- Current monoclonal antibody therapies (e.g., pembrolizumab, nivolumab) face limitations like poor tissue penetration and potential autoimmune responses due to large molecular size.
Purpose of the Study:
- To explore small-molecule, peptide, and PROTAC inhibitors targeting negative immune checkpoints.
- To highlight the advantages of smaller molecular inhibitors in overcoming the limitations of antibody-based therapies.
Main Methods:
- Review and description of small-molecule inhibitors targeting immune checkpoints.
- Analysis of peptide inhibitors for immune checkpoint modulation.
- Introduction of Proteolysis-Targeting Chimeras (PROTACs) for targeted protein degradation of immune suppressors.
Main Results:
- Small-molecule and peptide inhibitors demonstrate improved tissue penetration, oral bioavailability, and reduced immunogenicity compared to antibodies.
- PROTACs offer a novel mechanism by degrading proteins that suppress the immune response.
- The study covers inhibitors for multiple negative immune checkpoints: CTLA-4, PD-1, VISTA, TIM-3, BTLA-4, LAG-3, and TIGIT.
Conclusions:
- Small-molecule, peptide, and PROTAC inhibitors represent a promising next generation of immunotherapies.
- These novel drug modalities offer enhanced efficacy and safety profiles for cancer treatment and other immune-related diseases.
Related Concept Videos
01:27Tumor Immunotherapy
667
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
667
01:27Cytotoxic T Cells-mediated Immune Response
2.4K
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
2.4K