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The brain imports iron through the transferrin receptor. Antibody shuttle domains that bind that receptor raise brain exposure roughly ten to fifty-fold in primates and are already used in clinical Alzheimer's antibodies; the same engineering could carry antibody-drug conjugates or T-cell engagers to brain metastases.
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.
This review is the conceptual basis for trastuzumab, pertuzumab, HER2 antibody-drug conjugates and EGFR inhibitors, and for the HER3-mediated resistance that later drugs try to overcome.
This study confirmed HER2 as a prognostic marker and a therapeutic target, showed that immunohistochemistry could identify the patients, and extended the target to ovarian cancer. It set up the clinical development of trastuzumab and the HER2 testing that every breast cancer now receives.
Shares Slamon 1989: HER2/neu in human breast and ovarian cancer, Yarden and Sliwkowski 2001: untangling the ErbB signalling network, HER2-positive brain metastases, The brain: barrier and sanctuary.
Shares Slamon 1989: HER2/neu in human breast and ovarian cancer, Yarden and Sliwkowski 2001: untangling the ErbB signalling network, HER3, TROP2.
Shares Slamon 1989: HER2/neu in human breast and ovarian cancer, Yarden and Sliwkowski 2001: untangling the ErbB signalling network, HER2, HER2-positive breast cancer.
Shares Tucatinib, The brain: barrier and sanctuary, Trastuzumab deruxtecan, HER2-positive breast cancer.
Shares Blood-brain barrier (BBB), The brain: barrier and sanctuary, HER2-positive breast cancer, Non-small-cell lung cancer.
Shares HER2-positive brain metastases, Tucatinib, The brain: barrier and sanctuary, Trastuzumab deruxtecan.
Shares HER2-positive brain metastases, The brain: barrier and sanctuary, Trastuzumab deruxtecan, HER2-positive breast cancer.
Shares Yarden and Sliwkowski 2001: untangling the ErbB signalling network, TROP2, HER2, Antibody-drug conjugate (ADC).