Dr. Margaret Liu and colleagues have developed a dual-payload antibody-drug conjugate (DualADC) for chemo-immunotherapy utilizing 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 engineered antibody is linked to both a highly potent chemotherapy molecule and an immune boosting molecule allowing for a synergistic dual therapy delivery to a target tumor or cancer cell.
The inventors have preclinical data in TNBC and NSCLC xenograft immunocompetent and immunocompromised mouse models showing up to 90-100% reduction in tumor burden and also have preliminary PK and tox data in mouse models. The single cell RNA sequencing (scRNA-Seq) and chemocytokine Luminex assay demonstrated significantly increased immune cells infiltration and cytokines secretion in DualADC treated tumors. The inventors have developed a stable production cell line for the humanized CD276 antibody.
The technology specifically targets the CD276 receptor which is overexpressed in breast cancers, lung cancers, prostate cancers, and glioblastoma as compared to their normal tissues. The DualADC brings two therapeutic payloads directly to a targeted cancer cell for a synergistic effect: the immunotherapy (anti-CD276 antibody and immune boosting payload) re-activate NK and T immune cells and effector immune function in the tumoral microenvironment while the chemotherapy payload provides direct cancer cell killing and proliferation inhibition. This approach also overcomes immune checkpoint blocker resistance seen in PD1 and PDL1 immunotherapies.
Provisional patent filed: App.# 63/513,635