Complement
A cascade of blood proteins that punches holes in cells flagged by antibodies and calls in inflammatory cells. Rituximab uses it; tumours shield themselves with CD55 and CD59, and the cascade's own by-products recruit suppressive myeloid cells.
Diagram
Pick a product above a diagram to see the nodes it hits and the escape routes below the block. Hover or tap any node or arrow for what it is; every node opens its target, glossary entry or the pathway page. Violet boxes are druggable targets.
A demolition crew that follows the flags an antibody plants on a building: they blow holes in the walls (membrane attack complex) and call in the bulldozers (phagocytes). Tumours paint over the flags (CD55, CD59), and the noise of the demolition attracts the wrong kind of crowd (C5a-recruited suppressor cells).
What happens
In plain words, then the glossary entries the stage rests on. Chapter 6, Escaping the immune system: Every tumour that exists has already beaten the immune system once.
A cascade of blood proteins that punches holes in cells flagged by antibodies and calls in inflammatory cells. Rituximab uses it; tumours shield themselves with CD55 and CD59, and the cascade's own by-products recruit suppressive myeloid cells.
Complement in cancer. Complement is a cascade of blood proteins that punches holes in things marked by antibodies and calls in inflammatory cells. Therapeutic antibodies such as rituximab use it to kill cancer cells; tumours defend themselves with shields (CD46, CD55, CD59), and the cascade's own by-products (C5a) can recruit the myeloid cells that protect the tumour.
The molecular players
The proteins and genes at this stage, with their role and how many products act on each. Listed players come from the atlas; drawn players sit as nodes in the diagrams above.
CD20 is a B-cell marker; rituximab against it was the first antibody approved for cancer, in 1997.
CD38 is a myeloma surface enzyme and the target of daratumumab, which is now given as a quick under-the-skin injection.
PD-1 is a brake on T cells. Blocking it releases the immune system against the tumour and has cured some previously incurable cancers.
The receptor that macrophages depend on; blocking it shrinks tenosynovial giant cell tumour (a CSF1-driven tumour) and depletes tumour-supporting macrophages, though the latter has not yet helped patients with common cancers.
Where medicines act
Products grouped by the node they hit, most advanced first, with the cancers an approved product is linked to. Pick one above the diagram to see it light up.
- ObinutuzumabApprovedChronic lymphocytic leukaemiaDiffuse large B-cell lymphomaChronic lymphocytic leukaemia, first treatment
- RituximabApprovedChronic lymphocytic leukaemiaDiffuse large B-cell lymphomaMarginal zone lymphoma
- EpcoritamabApprovedDiffuse large B-cell lymphoma
- GlofitamabApprovedDiffuse large B-cell lymphoma
- Ibritumomab tiuxetanApprovedFollicular lymphoma
- MosunetuzumabApprovedDiffuse large B-cell lymphoma
- OdronextamabApprovedDiffuse large B-cell lymphoma
- OfatumumabApprovedChronic lymphocytic leukaemia
- +5 more at CD20 →
- CadonilimabApprovedCervical cancerGastric & gastro-oesophageal junction cancer
- CamrelizumabApprovedOesophageal cancerHepatocellular carcinomaNon-small-cell lung cancer
- Camrelizumab + rivoceranibApprovedHepatocellular carcinoma
- CemiplimabApprovedNon-small-cell lung cancerMelanomaPD-L1-high non-small-cell lung cancer without a driver mutation
- DostarlimabApprovedMismatch repair deficient (MSI-high) pancreatic ductal adenocarcinomaEndometrial cancerColorectal cancer
- IvonescimabApprovedNon-small-cell lung cancerColorectal cancerTriple-negative breast cancer (TNBC)
- NivolumabApprovedMelanomaNon-small-cell lung cancerRenal cell carcinoma
- PembrolizumabApprovedMismatch repair deficient (MSI-high) pancreatic ductal adenocarcinomaTriple-negative breast cancer (TNBC)Non-small-cell lung cancer
- +23 more at PD-1 →
How tumours escape
Records tied to this stage that describe resistance, evasion or tolerance. The resistance atlas lists the routes class by class.
- 2023translationalEPCORE NHL-1: epcoritamab, a subcutaneous CD20 x CD3 bispecific, in relapsed large B-cell lymphoma including after CAR-TJournal of Clinical Oncologychanged practice
- 2018rctMURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLLNew England Journal of Medicinechanged practice
Measured by
Biomarkers, tests and assays in the corpus that read this stage in a patient.
Open questions
What is not known at this stage: the atlas's own questions, the bottlenecks it bears on, and the ideas in the corpus that try to answer them.
- Should therapeutic antibodies be engineered for complement or against it?
- Does C5a blockade add to checkpoint inhibitors in patients?
- early clinicalclinicPlan the second CAR-T target before the first one is lost
Cell therapies fail when the tumour stops showing the marker they were built to find. Preparing an alternative product in advance would let doctors switch quickly.
- preclinical evidenceindustryBispecific antibodies that engage macrophages instead of T cells
Drugs that grab T cells and drag them onto tumours work well in blood cancers. The same trick aimed at tumour-eating cells might work where T cells are absent.
- speculativeregulatorAn abbreviated approval path for follow-on antibodies within a validated class
Once a class of antibody such as PD-1 blockers is proven, later copies could be approved on smaller trials showing equivalence, forcing price competition and freeing patients and money for genuinely new drugs.
Key evidence
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
- 2025rctAMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patientsNew England Journal of Medicinechanged practice
- 2025rctCEPHEUS: daratumumab quadruplet for newly diagnosed myeloma patients not having a transplant, with MRD-negativity as the main endpointNature Medicinechanged practice
- 2024rctPERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myelomaNew England Journal of Medicinechanged practice
- 2023translationalEPCORE NHL-1: epcoritamab, a subcutaneous CD20 x CD3 bispecific, in relapsed large B-cell lymphoma including after CAR-TJournal of Clinical Oncologychanged practice
- 2023rctSPOTLIGHT: zolbetuximab, the first Claudin 18.2 antibody, added to chemotherapy in gastric cancerThe Lancetchanged practice
- 2022rctPOLARIX: swapping vincristine for the antibody-drug conjugate polatuzumab vedotin in first-line treatment of diffuse large B-cell lymphomaNew England Journal of Medicinechanged practice
- 2020rctELEVATE-TN: acalabrutinib, alone or with obinutuzumab, against chemo-immunotherapy in untreated CLLThe Lancetchanged practice
- 2019rctCLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patientsNew England Journal of Medicinechanged practice
- 2019reviewContext-dependent roles of complement in cancerNature Reviews Cancer
- 2019rctMAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplantNew England Journal of Medicinechanged practice
- 2018rctMURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLLNew England Journal of Medicinechanged practice
src/data/mechanics-atlas.ts). Players, medicines, escape routes, tests, ideas and papers are resolved from the knowledge graph at build time through the stage's pathways, targets and terms, so every item here has its own page and sources. Where a section is missing, the corpus has no record tied to the stage yet. Nothing here is medical advice; see about and methodology. Stage 6.6 of 56.