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    RenNano® by Biocytogen: Fully Human VHHs Enabling Next-Gen Antibodies, ADCs, and Cell Therapies

    RenNano® by Biocytogen: Fully Human VHHs Enabling Next-Gen Antibodies, ADCs, and Cell Therapies

    April 01, 2025
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    The single VHH domain (~12–15 kDa), known for its ability to penetrate solid tumors and cross the blood-brain barrier, represents a promising modality for both diagnostic and therapeutic applications.

    Biocytogen’sRenNanoMice: A Fully Human Heavy Chain-Only Platform for VHH Discovery

    RenNano mice were developed by genetically modifying the antibody constant region in RenMab mice. Upon immunization, RenNano mice produce fully human heavy-chain-only antibodies (HCAbs) capable of antigen binding without light chains.These RenNano-derived HCAbs feature:

    • Diverse CDR3 sequences
    • Excellent specificity and affinity for various epitopes
    • Robust biological activity in both in vitro and in vivo systems
    • Compatibility with drug modalities such as bispecific/multispecific antibodies, antibody-drug conjugates (ADCs), and cell therapies

    In February 2023, Biocytogen launched the "Nano 100 Project", aiming to develop fully human therapeutic VHHs targeting over 100 distinct antigens.

    Case Study 1: VEGF-A HCAbs

    VEGFA (referred to as VEGF hereafter) is a key member of the vascular endothelial growth factor family, which also includes VEGFB, VEGFC, VEGFD, and placental growth factor (PLGF/PGF). VEGF is overexpressed in several cancers, including:

    • Lung cancer
    • Breast cancer
    • Gastrointestinal cancer
    • Renal cancer
    • Ovarian carcinoma

    Benchmark: Bevacizumab analog

    Our anti-VEGFA HCAbs, derived from RenNano mice, demonstrate superior blocking activity compared to the benchmark.

    ▷Binding Affinity and Blocking Activity

    Case Study 2: DLL3 HCAbs

    Delta-like ligand 3 (DLL3) is a negative regulator of the Notch signaling pathway and is aberrantly expressed on the cell surface of most neuroendocrine prostate cancers (NEPC) and other small cell carcinomas.

    Benchmark: AMG 757 analog

    Our anti-DLL3 HCAbs exhibit:

    • Strong binding to SCLC cells
    • Recognition of diverse DLL3 epitopes

    ▷High Affinity in Tumor Cells

    ▷ Epitope Binning Assay

    Case Study 3: TFR1 HCAbs

    TFR1, also known as CD71, is a transmembrane glycoprotein involved in cellular iron uptake and is often upregulated in various cancers, including breast, lung, and colorectal cancers, making it a potential target for cancer therapy.

    Beyond its role in cancer, TFR1 is highly expressed in blood-brain barrier (BBB) endothelial cells, where it mediates ligand-independent, receptor-mediated transcytosis. Transferrin binds to TFR1, is internalized, and transported across the BBB, enabling the delivery of transferrin and associated therapeutics into the brain. This mechanism offers a promising strategy for treating neurodegenerative diseases like Alzheimer’s and Parkinson’s, as well as brain tumors.

    Our anti-TFR1 HCAbs demonstrate:

    • Superior BBBpenetrationin vivocompared to benchmark antibodies.

    • High affinity for both human and monkey TFR1.

    • Significantly enhanced BBB penetration in the monovalent form compared to the bivalent form.

    • Versatility for both non-conjugated (e.g., fusions, bispecifics) and conjugated payload delivery (e.g., AOCs, small molecules).

    ▷ Superior BBB penetration compared to the benchmark antibody

    Superior BBB penetration of TFR1 HCAbs compared to the benchmark antibody

    ▷ The monovalent form exhibits significantly better BBB penetration than the bivalent form

    RenNano Platform Antibody Library

    Biocytogen is actively seeking collaborations with global pharmaceutical and biotech companies in VHH-related therapeutics, including cell therapies, BBB shuttles, bispecific and multispecific antibodies, ADCs, and RACs. Together, we aim to develop novel drugs with first-in-class and best-in-class potential.

    Feel free to contact us for more information or to explore co-development and licensing opportunities!