Monoclonal Antibodies Binding to Transferrin Receptor (TfR) for Therapeutic Protein Delivery across Blood-Brain Barrier


Blood-brain barrier (BBB) limits brain entry and is one of the major hurdles in developing antibody and protein-based therapeutics for central nervous system (CNS) diseases. UTHealth researchers identified and engineered monoclonal antibodies binding to transferrin receptor (TfR) but not affecting transferrin (Tf) binding to TfR. An engineered monovalent anti-TfR antibody fused with a VEGF-Trap protein improved the delivery of the protein fusion crossing the BBB.


Antibody and protein-based drug modalities are promising options for treating diseases in the central nervous system (CNS), yet only a limited number of therapies are approved in this category. One of the major obstacles to developing antibody and protein-based therapeutics for CNS diseases is the low brain entry, due to the existence of blood-brain barriers (BBB). The transferrin receptor (TfR) is known for receptor-mediated transcytosis (RMT), which successfully aided the delivery of antibody and protein therapeutics crossing the BBB in both mouse and primate models. There is a demand for an engineered anti-TfR antibody to improve the brain entry and efficacy of cancer anti-angiogenic therapy.

Significance and Impact

UTHealth researchers identified anti-TfR antibodies specifically binding cell-surface-expressed TfR proteins but not competing with Tf binding. Using one of the anti-TfR antibodies, they engineered a bispecific construct named VEGF-Trap/moAb4 that improved the delivery of aflibercept across the BBB by more than 10-fold. VEGF-Trap/moAb4 also demonstrated significant improvement in inhibiting angiogenesis in a mouse tumor model.

Technology Highlights

The bispecific construct using the novel anti-TfR antibody can improve protein delivery crossing the BBB.
The TfR antibody-fusion protein was effectively distributed in the brain parenchyma.

Potential Applications

The existence of the BBB is one of the main hurdles that causes limited brain penetration of antibody-based therapies. The novel anti-TfR antibody binds TfR but does not compete with Tf binding, which could facilitate antibody and protein-based therapeutic agents crossing the BBB. The improved brain entry potentially benefits antibody and protein-based drug modalities treating CNS diseases, including cancer, neurodegenerative diseases, autoimmune diseases, nervous system disease, and genetic disorders.

Related Publication:  Zhao et al. MAbs. 14(1): 22057269 (2022)


Intellectual Property Status

Patent filed

PCT Publication No:  PCT/US2022/076380

Available for licensing.

About the Inventors

Zhiqiang An, Ph.D.

Vice President of Drug Discovery at UTHealth Houston

Ningyan Zhang, Ph.D.

Professor at UTHealth Houston and Co-Director of the CPRIT Therapeutic Antibody Core.

Patent Information:

The preceding is intended to be a non-confidential and limited description of a novel technology created at the University of Texas Health Science Center at Houston (UTHealth). This promotional material is not comprehensive in scope and should not replace company’s diligence in a thorough evaluation of the technology. Please contact the Office of Technology Management for more information regarding this technology.
For Information, Contact:
Yu Ouyang
Technology Commercialization Analyst
University of Texas Health Science Center At Houston
Zhiqiang An
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