TFR1 Heavy-Chain-Only Antibodies: Innovating Cancer Therapy & Brain Drug Delivery
Transferrin Receptor 1 (TFR1), also known as CD71, is a critical transmembrane glycoprotein responsible for cellular iron uptake and metabolic regulation. It plays a key role in cell proliferation and differentiation. Overexpressed in multiple tumors—including breast, lung, colorectal cancers, as well as hematologic malignancies—TFR1 is closely associated with tumor proliferation, invasion, and metastasis (Shen et al., 2018, Daniels et al., 2012, Chirasani et al., 2008) . This makes it a promising biomarker and therapeutic target for cancer treatment.
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.
To enhance BBB penetration,?Biocytogen?has developed TFR1 heavy-chain antibodies (HCAbs) using its fully human heavy-chain-only antibody discovery platform,?RenNano?.?These antibodies demonstrate significant potential for treating neurological diseases, supported by promising results from?in vivo?studies.
Key Highlights of TFR1 HCAbs:
Top TFR1 antibodies exhibit superior BBB penetration compared to a JR-141 analog?in vivo, alongside high affinity for human and monkey TFR1.
? Superior BBB penetration compared to the benchmark antibody
? The monovalent form exhibits significantly better BBB penetration than the bivalent form
? Versatile for both non-conjugated shuttling (e.g., fusions or bsAbs) and conjugated payload shuttling (e.g., AOCs or small molecules)
In Vivo Delivery Evaluation Studies
Download our TFR1 HCAbs poster now to discover more!
References
Chirasani, S. R., et al. “Transferrin-receptor-mediated iron accumulation controls proliferation and glutamate release in glioma cells.”?Journal of Molecular Medicine?87 (2009): 153-167.
Shen, Ying, et al. “Transferrin receptor 1 in cancer: a new sight for cancer therapy.”?American journal of cancer research?8.6 (2018): 916.
Daniels, Tracy R., et al. “The transferrin receptor and the targeted delivery of therapeutic agents against cancer.”?Biochimica et Biophysica Acta (BBA)-General Subjects?1820.3 (2012): 291-317.