Therapeutic antibodies that block checkpoint receptor-ligand interactions, releasing the brakes on anti-tumor immunity.
ICIs work by blocking the interaction between checkpoint receptors and their ligands. Anti-PD-1 antibodies (pembrolizumab, nivolumab) bind PD-1 on T cells, preventing PD-L1 engagement. Anti-PD-L1 antibodies (atezolizumab, durvalumab) bind the ligand directly.
The result is the same: T cells no longer receive the inhibitory signal, allowing them to recognize and kill tumor cells. Anti-CTLA-4 (ipilimumab) works earlier in the immune response, preventing suppression during T cell priming.
How They Work: Checkpoint inhibitors are antibodies that block the "handshake" between checkpoint receptors (PD-1, CTLA-4) and their ligands (PD-L1, CD80). This releases the "brakes" on immune cells, allowing them to attack cancer.
Types: Anti-PD-1, anti-PD-L1, anti-CTLA-4, and newer agents targeting LAG-3, TIM-3, TIGIT.
ICIs have achieved durable responses in melanoma, NSCLC, RCC, and many other cancers–sometimes lasting years. But most patients do not respond, and current biomarkers cannot reliably identify who will benefit.
PD-L1 expression by IHCLoading... is approved as a companion diagnosticLoading..., yet only ~41% of 'high expressers' respond in NSCLC. This means the majority of patients meeting the biomarker threshold receive ineffective therapy with potential immune-related adverse events.
The Success: Checkpoint inhibitors have revolutionized cancer treatment, producing durable responses in melanoma, lung cancer, kidney cancer, and many others.
The Limitation: Only 20-40% of patients respond, even in approved indications. We need better ways to identify responders.
The fundamental issue is that ICIs work by blocking interactions–yet the approved biomarker measures expression. A tumor expressing PD-L1 without nearby T cells has no interaction to block.
iFRETLoading... addresses this directly by measuring whether the checkpoint is functionally engaged. Patients with high PD-1/PD-L1 interaction–the actual therapeutic target–show improved outcomes regardless of expression score.
The Problem: PD-L1 expression testing is used but imperfect. Many "negative" patients respond; many "positive" patients don't.
The Insight: Checkpoint inhibitors block checkpoint INTERACTIONS. If the checkpoint isn't engaged, blocking it won't help. Measuring engagement directly should predict response better than measuring expression.
Patient Selection: QF-Pro enables functional biomarker-based patient selection for ICI therapy. Clinical validation showed iFRET-measured PD-1/PD-L1 interaction predicted survival (P=0.05[3]) while expression did not (P=0.87[3]). Patients classified as "PD-L1 negative" by IHC showed FRET-detectable engagement–identifying potential responders currently denied therapy.
Click citation numbers to view full references in QF-Pro Applications & Clinical EvidenceLoading...
Patient selection: QF-Pro can identify ICI responders that expression testing misses. Patients labeled "PD-L1 negative" often have detectable checkpoint engagement–and may respond to immunotherapy.
