ADC payload neutralisers
An ADC payload neutraliser is an antibody given alongside an ADC that mops up the poison once it leaks into the bloodstream, so the ADC can hit the tumour with fewer side effects.
Free payload released from ADCs in circulation drives much of their toxicity (neuropathy, rash, hyperglycaemia with MMAE; neutropenia with SN-38). A neutralising antibody with high affinity for the free payload but not the conjugated form could widen the therapeutic index without changing the ADC. Generate Biomedicines' GB-4362, an AI-designed MMAE neutraliser, entered the clinic in 2026 with FDA Fast Track designation for enfortumab vedotin-induced toxicity in urothelial cancer.
How it works
Antibody binds the released small-molecule payload in plasma, preventing uptake by normal tissue; conjugated payload on the ADC remains unaffected.
- Adds to existing approved ADCs without reformulation
- Could permit higher ADC doses
- Early clinical stage
- Payload-specific: one neutraliser per payload class
- Risk of blunting bystander killing if payload diffuses into plasma from the tumour
Latest papers
topQuery for this technology: (TITLE:"ADC payload neutralisers" OR ABSTRACT:"ADC payload neutralisers") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about ADC payload neutralisers, not a curated reading list.