Immune Checkpoint Inhibitor
Immune checkpoint inhibitors (ICIs) are a class of immunotherapy drugs that block the action of specific proteins (checkpoints) that regulate the immune system, thereby preventing cancer cells from evading immune detection.
Mechanism of Action
ICIs work by inhibiting checkpoint pathways such as:
- PD-1/PD-L1 axis: Prevents tumor cells from deactivating T-cells.
- CTLA-4: Enhances T-cell activation in lymph nodes.
Clinical Applications
ICIs are standard of care for various malignancies, including:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
Recent Advances in Adjuvant Therapy
Significant progress has been made in combining novel modalities with established ICIs for adjuvant-therapy in high-risk patients.
- Personalized mRNA Vaccines: Research into personalized neoantigen-targeting vaccines aims to stimulate a specific immune response against tumor antigens.
- Combination with Keytruda: Recent Phase 3 trial data indicates positive outcomes when combining personalized mRNA vaccines with Keytruda (pembrolizumab) for resected melanoma.
- Moderna Merck Collaboration: A notable development involves the collaboration between Moderna and Merck & Co. on an mRNA cancer vaccine candidate (Intismeran/Autogene) used in conjunction with Keytruda.
- Clinical Significance: This approach targets residual disease after surgical resection, aiming to reduce recurrence rates in melanoma patients.
Related Concepts
- T-cell exhaustion
- Neoantigen
- adjuvant-therapy
- pembrolizumab