Use the brain's own transport door to carry antibody drugs across
The brain has natural transport doors for iron. Attaching a key that fits those doors can smuggle large drug molecules in, a trick now working in Alzheimer's medicines.
Transferrin receptor-binding shuttle domains raise brain exposure of antibodies roughly ten to fifty-fold in primates and are being used in clinical Alzheimer's antibodies and enzyme replacement therapies. Applying the same engineering to antibody-drug conjugates or T-cell engagers directed at brain metastasis antigens is a well-defined, if demanding, protein engineering task with a real precedent from another disease area.
- The brain: barrier and sanctuary · Most drugs cannot cross into the brain, so brain tumours and brain metastases lag every other site.
- The undruggable drivers · The proteins that drive most cancers, such as MYC, mutant p53 and most RAS variants, still have no good drug.
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not linked directly; found by shared links- IdeaSystemic-first management of HER2-positive brain metastases
Shares HER2-positive brain metastases, Tucatinib, The brain: barrier and sanctuary, Trastuzumab deruxtecan.
- TrialDESTINY-Breast12
Shares HER2-positive brain metastases, The brain: barrier and sanctuary, Trastuzumab deruxtecan, HER2-positive breast cancer.
- IdeaBrain metastases included by default in every solid-tumour trial
Shares Tucatinib, The brain: barrier and sanctuary, Trastuzumab deruxtecan, HER2-positive breast cancer.
- ProductTrastuzumab duocarmazine
Shares Trastuzumab deruxtecan, HER2, HER2-positive breast cancer, Antibody-drug conjugate (ADC).
- TrialHER2CLIMB
Shares HER2-positive brain metastases, Tucatinib, The brain: barrier and sanctuary, HER2.
- IdeaBuild a human model of the barrier that guards the brain fluid
Shares Blood-brain barrier (BBB), The brain: barrier and sanctuary, HER2-positive breast cancer, Non-small-cell lung cancer.
- PersonBob T. Li
Shares Trastuzumab deruxtecan, HER2, Antibody-drug conjugate (ADC), Non-small-cell lung cancer.
- PairingTucatinib + trastuzumab + capecitabine for brain metastases
Shares HER2-positive brain metastases, Tucatinib, HER2-positive breast cancer.