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Cancer spreading along the linings of the brain has no treatment that reliably controls it. Injecting engineered immune cells directly into the brain fluid, through a small reservoir, reaches it.
Intraventricular delivery of HER2-directed CAR-T cells via an Ommaya reservoir has produced responses in leptomeningeal metastasis in early trials at City of Hope, and intrathecal chemotherapy is long-established. Local delivery avoids the barrier entirely, gives high local cell dose and appears to reduce systemic cytokine toxicity.
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 CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target), B7-H3, The brain: barrier and sanctuary, CAR-T cell therapy.
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 Slamon 1989: HER2/neu in human breast and ovarian cancer, Yarden and Sliwkowski 2001: untangling the ErbB signalling network, B7-H3, HER2.
Shares City of Hope, CAR-T cell therapy, Glioma & glioblastoma.
Shares City of Hope, CAR-T cell therapy, Glioma & glioblastoma.
Shares Metastasis is understood least and studied last, The brain: barrier and sanctuary, Glioma & glioblastoma, HER2-positive breast cancer.
Shares Yarden and Sliwkowski 2001: untangling the ErbB signalling network, B7-H3, HER2.