Antibody Engineering Program

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

FY25 Antibody Engineering Program (AEP) Highlights. In FY25, the Antibody Engineering Program (AEP), in collaboration with NCI labs, published three research articles: Duan et al., Molecular Therapy Oncology, 2024; Basuli et al., Bioconjugate Chemistry, 2024; Fayn et al., Advanced Science, 2025. Targeting HPV-Related Cancers with CAR-T Nanobodies HPV E6 and E7 oncoproteins are key targets for HPV-related cancers. Duan et al. developed novel TCR mimic (TCRm) nanobodies in a CAR-T format targeting the HPV16 E6 peptide (E6)-HLA-A*02:01 complex. Two nanobodies, F5 and G9, were isolated from a dromedary camel phage display library constructed and provided by Dr Mitchell Ho's lab at the NCI Laboratory of Molecular Biology. Nanobody F5 showed stronger binding and specificity toward HPV-positive cell lines. CAR-T cells using F5 effectively killed these target cells in vitro via NFAT and NF-kB signaling, and suppressed tumor growth in mouse models. This approach offers a promising new strategy for treating HPV-16+ cancers including cervical cancer. Site-Specific Nanobody Labeling for Imaging and Beyond. Fayn et al, in collaboration with the AEP, developed a modular nanobody labeling platform using novel conjugation chemistry. The system combines a target-binding nanobody (called HN3 targeting GPC3 in hepatocellular carcinoma, developed by Dr Mitchell Ho's lab at the NCI) with a self-labeling module that binds to a synthetic high-affinity tag. This enables site-specific attachment of various functional groups (e.g., fluorophores, chelators) without disrupting antigen recognition. These constructs successfully targeted liver cancer models in mice, allowing non-invasive imaging. This flexible labeling strategy can be applied to a wide range of diagnostic and therapeutic applications.