Ipilimumab acts at the T-cell commitment step against Treg over-correction
Position 4 of the cancer-immunity cycle is the commitment threshold. A T cell either crosses it and becomes a fully committed anti-tumour effector or holds back. The decision is gated by the CD28/CTLA-4 balance at the synapse. When regulatory amplitude exceeds what the system is correcting, the cycle oscillates between activation and brake instead of completing; that is what over-correction names. Ipilimumab occupies B7, blocking CTLA-4 from engaging it, so CD28 costimulation can fire. The drug matrix places anti-CTLA-4 at P4 for this reason.
What this is
The Living Scorecard is Encounter's open record of structural predictions. Each hypothesis names a candidate intervention, where in the cycle it is predicted to act, the failure mode it is predicted to address, and the evidence available when the prediction was made.
Predictions are locked with timestamps before they can be tested. Encounter generates them daily, many more than any one person can chase, so the field can see what the framework claims structurally, ahead of the data. Some will hold. Some will be refuted. Both stay on the page. The point is that each prediction is committed before the answer is known, so the data that arrives later can confirm or refute it.
Structural argument
Position 4 sits in the Pot outer regime (capacitor) of the cancer-immunity cycle. Its operational character at this slot is homeostat. The CD28/CTLA-4 balance keeps a setpoint that gates the T cell's commitment to anti-tumour effector lineage. Ipilimumab releases the CTLA-4 brake by occupying B7, so CD28 costimulation can fire. That counters over-correction, the failure mode where regulatory amplitude exceeds what the system is correcting and the cycle oscillates instead of completing. The intervention's regime-type class lines up with the position's outer regime, and failure_over_correction belongs to the homeostat sub-regime's failure set.
rule_r13(required) — Combinatorial candidate is grounded in R13's position-to-state table, which determines which interventions are structurally addressable at which positions.
Substrate
- Domain
- domain_cellular_biology
- Cycle
- cycle_l4_canonical
- Position(s)
- position_p4
- Failure modes
- failure_over_correction
Evidence at generation
"ipilimumab" AND "cancer immunotherapy"
- PMID 38828984
Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma.
- PMID 35810989
Colorectal cancer immunotherapy-Recent progress and future directions.
- PMID 35403841
Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer.
- PMID 29778737
Cancer immunotherapy efficacy and patients' sex: a systematic review and meta-analysis.
- PMID 22193102
Cancer immunotherapy comes of age.
Targets: CHEMBL2364164
inhibitor
ipilimumab cancer immunotherapy
- NCT04090775
Metastatic Prostatic Adenocarcinoma
Primary: Primary endpoint: PSA decline
- NCT04943848
Diffuse Intrinsic Pontine Glioma
Primary: Safety and Tolerability: Dose limiting toxicities of rHSC-DIPGVax
- NCT03416244
Esophageal Cancer
Primary: Overall survival
- NCT06492421
Lung Cancer
Primary: pCR rate for the study groups
- NCT05219435
Urothelial Cancer
Primary: progression-free survival (PFS)
Status timeline
- Draft2026-05-28T23:02:09Z
Generated by combinatorial walker (v0.1.0) after the v0.1.1 fix that respects verb_target on drug-matrix entries and sources failure modes from each position's sub-regime class.
by system
- Published2026-05-28T23:02:09Z
Replaces the earlier ipilimumab at P1 hypothesis, which was a structural error. The canonical drug matrix places anti-CTLA-4 at P4 (commitment threshold), not P1 (antigen release). P1 is for STING agonists, oncolytic viruses, and immunogenic chemotherapy. The prior YAML has been removed and the Sanity document deleted.
by raimo