From the Guidelines
PD-1 targeted therapy is a type of immunotherapy that works by blocking the PD-1 receptor, preventing it from binding to its ligand, PD-L1, and thereby disrupting the signaling that inhibits the immune response against cancer cells.
Key Points
- PD-1 targeted therapy is used to treat various types of cancer, including non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and squamous cell lung cancer (SqCLC) 1.
- The therapy involves the use of monoclonal antibodies, such as pembrolizumab and nivolumab, that target the PD-1 receptor or its ligand, PD-L1 1.
- The goal of PD-1 targeted therapy is to enhance the body's immune response against cancer cells, leading to improved overall survival and progression-free survival rates 1.
- The therapy has been shown to be effective in patients with high PD-L1 expression, and its use has been integrated into treatment guidelines for various types of cancer 1.
Examples of PD-1 Targeted Therapies
- Pembrolizumab: a PD-1-blocking antibody approved for the first-line treatment of metastatic NSCLC in patients with high PD-L1 expression 1.
- Nivolumab: a PD-1 immune checkpoint inhibitor monoclonal antibody approved for the treatment of advanced RCC 1.
Important Considerations
- PD-1 targeted therapy can be associated with immune-related adverse events (irAEs), which can involve any organ or system of the body 1.
- The incidence and onset of irAEs vary based on the specific therapy and patient population, and a high level of suspicion is required to diagnose and manage these events 1.
From the Research
Overview of PD-1 Targeted Therapy
- PD-1 (Programmed Death-1) is an inhibitory receptor expressed on activated T cells, which can reverse immune suppression and release T cell activation 2.
- PD-1 targeted therapy, also known as immune checkpoint inhibitors, has shown unprecedented success in a wide variety of human cancers, including non-small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), and lymphoma 2, 3, 4.
Mechanism of PD-1 Targeted Therapy
- PD-1 is activated by its ligands, mainly PD-L1, which recruits the phosphatase SHP-2 and leads to inhibition of T cell proliferation, activation, cytokine production, and cytotoxic T lymphocytes (CTLs) killer functions 3.
- Tumor cells can hijack the PD-1/PD-L1 pathway to escape host immune surveillance by overexpressing PD-L1, providing a scientific rationale for clinical application of immune checkpoint inhibitors in oncology 3.
Clinical Applications of PD-1 Targeted Therapy
- Antibodies targeting PD-1/PD-L1, such as nivolumab, pidilizumab, and pembrolizumab, have shown remarkable objective response and durable remission with acceptable toxicity profile in various types of cancer 2, 3, 4.
- PD-1 targeted therapy has been effective in treating melanoma, lymphoma, and mismatch-repair deficient tumors, with ongoing clinical trials evaluating its role in other types of cancer 3, 4.
Challenges and Future Perspectives
- Despite the success of PD-1 targeted therapy, most patients are still refractory to anti-PD-1/PD-L1 therapy, highlighting the need for identifying predictive biomarkers and designing rational combination therapies 3.
- Advanced nanotechnology has been developed to enhance the efficiency of PD-1 targeted therapy, including nanoprobe-assisted analysis of PD-L1 and functional nanocarriers for targeted delivery of PD-L1 immune checkpoint inhibitors 5.