Targeted Anti-ROR2 Antibodies for Precision Cancer Therapy

Enables Selective Targeting of ROR2-Positive Tumors Using High-Affinity Antibodies and Antibody-Drug Conjugates

These targeted anti-ROR2 antibodies enable precision cancer therapy by selectively engaging ROR2-positive tumors with high-affinity antibodies and antibody-drug conjugates (ADCs). The ADC market is projected to grow from $13.5 billion to $32.7 billion by 2035 at a CAGR of 9%, primarily driven by increasing number of cancer cases and the demand for safer, more efficient medicines. ROR2 is a receptor whose expression is strongly associated with tumor progression in multiple cancers, and its expression is limited in normal adult tissues. Since ROR2 is largely absent from normal adult tissues, it is an attractive tumor-associated antigen for both therapeutics and diagnostics. Therapeutic progress is limited by the absence of antibodies with sufficiently high affinity and exclusive specificity for ROR2. Robust, selective ROR2 binders are required to enable safe and effective delivery of cytotoxic payloads or immune effector functions to ROR2 positive tumors.

Researchers at the University of Florida have developed high-affinity, sequence-defined anti-ROR2 antibodies. This overcomes the current shortage of sequence-defined, tumor-specific ROR2-targeting agents and creates a platform for ROR2-directed cancer therapeutics, diagnostic assays, and molecular imaging applications to selectively bind ROR2-positive tumors.

Application

ROR2-targeted therapeutics and diagnostics for precision oncology, including monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and T-cell engagers (TCEs) to selectively detect or kill ROR2-positive tumors while sparing normal tissues

Advantages

• Provides sub-nanomolar binding, supporting robust and sustained tumor engagement
• Exhibits binding specificity for ROR2 with no detectable cross-reactivity with ROR1 or other cell surface antigens in tested assays, reducing off-target risk
• Allows use of standard mammalian expression systems, facilitating scalable manufacturing
• Fully characterized sequence enables a scaffold for therapeutic, diagnostic, and imaging applications targeting tumors expressing ROR2

Technology

These targeted anti-ROR2 antibodies deliver a precision cancer therapy that selectively binds ROR2-positive tumors through high-affinity mAbs, ADCs, TCEs, and other antibody modalities. The antibodies are derived from rabbit variable domains selected for high-affinity and specificity to human ROR2, then grafted onto human antibody constant domains to generate full-length IgG molecules suitable for therapeutic development. The antibodies are equipped with a short peptide tag at its C-terminus, serving as a defined enzymatic conjugation site for covalent attachment of cytotoxic drugs, imaging agents, or other functional payloads. This format enables defined drug-to-antibody ratios and consistent ADC assembly. The antibodies were selected against the extracellular portion of human ROR2 for high affinity and demonstrate exclusive specificity, with no detectable cross-reactivity with closely related receptors, such as ROR1. The format is compatible with standard mammalian expression systems, providing a platform for the development of ROR2-targeted mAbs, ADCs, TCEs, other antibody-based therapeutics, and companion diagnostics.

Publications

• Peng et al. (2017), J. Mol. Biol. 429, 2954-2973
• Goydel et al. (2020), J. Biol. Chem. 295, 5995-6006