PD-1 antibodies are immunotherapy drugs that target the PD-1 pathway, a critical checkpoint in the immune system. PD-1, a receptor on T cells, interacts with its ligands PD-L1 and PD-L2 to downregulate immune responses. Blocking this interaction with PD-1 antibodies prevents the inhibition of T cells, enhancing their ability to attack cancer cells.
Mechanism of Action
- PD-1 antibodies block PD-1 from binding to PD-L1/PD-L2.
- This blockade reactivates T cells, promoting anti-tumor activity.
Approved PD-1 Antibodies
- Nivolumab (Opdivo): Used for melanoma, NSCLC, RCC.
- Pembrolizumab (Keytruda): Used for melanoma, NSCLC, HNSCC.
- Cemiplimab (Libtayo): Used for CSCC, NSCLC.
Adverse Effects
- Immune-related adverse events (irAEs) include:
- Skin: Rash, itching.
- Gastrointestinal: Colitis, diarrhea.
- Hepatic: Hepatitis.
- Endocrine: Thyroid disorders.
- Pulmonary: Pneumonitis.
Biomarkers for Response
- High PD-L1 expression.
- High tumor mutational burden (TMB).
- Microsatellite instability-high (MSI-H) status.
Resistance Mechanisms
- Primary resistance: Tumor-intrinsic factors prevent initial response.
- Acquired resistance: Tumors adapt, leading to loss of response.
Clinical Application
- Used alone or in combination with chemotherapy, radiation, or other checkpoint inhibitors.
- Effective in cancers with high mutational burden or specific genetic markers.
Future Directions
- Research on combination therapies, novel biomarkers, and new checkpoint inhibitors.
- Exploring use in chronic infections and autoimmune diseases.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|