Humanized SSTR2 mAb and ADC to target SSTR2+ tumorsTargeted humanized mAbs and ADCs for cancer treatment The Liu Lab Dr. Xiaoguang “Margaret” Liu applies her industry experience (Lonza, Merck, and Life Technologies) in cell line and process development towards her lab’s focus on targeted anti-cancer therapies including monoclonal antibodies, antibody-drug conjugates, and gene therapies.
DualADC platform The Liu lab has developed a dual-payload antibody-drug conjugate (DualADC) platform for conjugating both chemotherapy and immunotherapy drugs to any antibody backbone. The platform utilizes traditional lysine and cysteine residue conjugation sites while employing novel or traditional linkers. The platform enables a drug antibody ratio (DAR) for a subject antibody ranging from 2-14.
Humanized-CD276 (B7-H3) mAb, ADC, and DualADC The Liu lab has developed a new humanized antibody that targets CD276, a surface receptor that is overexpressed in Triple-negative Breast Cancers (TNBCs), lung cancer (including non-small cell lung cancer - NSCLC), glioblastoma (GBM), and prostate cancer (PC). The inventors have developed a stable CHO production cell line for a humanized-CD276 mAb. Utilizing the DualADC platform, the engineered antibody is linked to both a highly potent chemotherapy molecule and an immune boosting molecule enabling a synergistic dual therapy delivery to a target tumor or cancer cell.
For the CD276-DualADC, her lab has preclinical data in TNBC and NSCLC immunocompetent, immunocompromised, patient-derived xenograft (PDX), and metastases mouse models showing up to 90-100% reduction in tumor burden, including metastases reduction, with no recurrence. They also have preliminary PK and tox data in mouse models. Studies have shown minimal off-targeting in 33 normal human organ and tissue models. The single cell RNA sequencing (scRNA-Seq) and chemo cytokine Luminex assay demonstrated significantly increased immune cells infiltration and cytokines secretion in CD2766-DualADC treated tumors.
Humanized-SSTR2 mAb, ADC, and DualADC The Liu lab has developed a new humanized antibody that targets SSTR2, somatostatin receptor 2, a powerful target for treating Neuroendocrine Tumors (NETs) and meningiomas. The inventors have developed a stable CHO production cell line for the humanized SSTR2 antibody.
Her lab has xenograft meningioma studies showing traversal of the blood brain barrier and specific tumor targeting with murine-anti-human-SSTR2 mAb. For the Humanized SSTR2-Dual ADC, her lab has preclinical data in NET in vitro studies with NET and meningioma xenograft mouse models studies ongoing.
Additional programs in process: mAbs: lipolysis simulated lipoprotein receptor (LSR), CD151, CD97, CD146, CD9, CD109, CD166, FGFR4, EpCAM, CD47 Targeted drug delivery: mAb-EV or mAb-LNP Cancer mitochondrial luminopotogenetics: mitochondria-targeted gene therapies delivered with AAVs or mAB-Exo-AAV Patents
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