Patrys

Technology

Deoxymab Platform

Patrys’ deoxymab platform is based on an antibody called 3E10 that was originally isolated from a mouse model of a human autoimmune disease called systemic lupus erythematosus (SLE). Deoxymab antibodies exhibit several distinctive properties ideal for human therapeutic applications

  • DNA targeting
  • Blood-brain barrier
  • Inhibit NETosis

These unusual properties have opened up a range of therapeutic approaches for the treatment of cancer and NETosis-driven inflammatory diseases.

Patrys has developed humanised versions of deoxymabs, both a full-sized IgG and smaller antibody fragments, which it is developing for human therapeutic applications.

DNA Targeting

Deoxymabs are anti-DNA antibodies and as such have the ability to target various DNA processes inside cells (cancer cells as well as others, including neutrophils) such as DNA repair and NETosis.

Deoxymabs are attracted to cancer cells that do not have traditional cell surface markers of disease. Instead, they bind to fragments of DNA that are released from cells when they die (the rate of cell death is much higher in cancer cells than in healthy cells), meaning that deoxymabs can be used to target cancer cells regardless of their location or type.

Blood Brain Barrier

The blood-brain barrier (BBB) presents a significant challenge in treating primary and secondary brain cancers as it limits the passage of drugs and antibodies into the brain. Deoxymabs possess the ability to cross the BBB and reach neural tissues, opening new avenues for treating brain cancers.

Inhibit NETosis

Excessive immune cell web formation (NETosis) contributes to the pathogenesis of cancer and many infectious, inflammatory, and autoimmune diseases. Deoxymabs significantly reduce NET (neutrophil extracellular trap) formation in human neutrophils and reduce symptoms in an animal model of Anti‑Neutrophil Cytoplasmic Antibody (ANCA) associated Vasculitis (AAV). Notably, deoxymabs do not impair neutrophil activity which is important in preserving overall immune function.

Key Publications

Xiaoyong Chen, Benedette J. Cuffari, Valentina Dubljevic, Anupama Shirali, Jiangbing Zhou, James A. Campbell, Stephen C. Suits, Kim M. O’Sullivan, James E. Hansen; Inhibition of NETosis by a Nuclear-Penetrating Anti-DNA Autoantibody. Immunohorizons 1 June 2022; 6 (6): 356–365.

Z Rattray, G Deng, S Zhang, A Shirali, CK May, X Chen, BJ Cuffari, J Liu, P Zou, NJW Rattray, CH Johnson, V Dubljevic, JA Campbell, A Huttner, JM Baehring, J Zhou and JE Hansen. ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody. JCI Insight. 2021;6(14):e145875

Z Rattray, V Dubljevic, NJW Rattray, DL Greenwood, CH Johnson, JA Campbell, JE Hansen. Re-engineering and evaluation of anti-DNA autoantibody 3E10 for therapeutic applications. Biochem Biophys Res Commun, 2018, 496(3): 858-864

Z Chen, JM Patel, PW Noble, C Garcia, Z Hong, JE Hansen, J Zhou. A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors. Oncotarget, 2016, 7(37): 59965-59975.

PW Noble, S Bernatsky, AE Clarke, DA Isenberg, R Ramsey-Goldman, JE Hansen. DNA-damaging autoantibodies and cancer: the lupus butterfly theory. Nature Reviews Rheumatology, 2016, 12(7): 429-34.

RH Weisbart, G Chan, G Jordaan, PW Noble, Y Liu, PM Glazer, RN Nishimura, JE Hansen. DNA-dependent targeting of cell nuclei by a lupus autoantibody. Sci Rep.,  2015, 5: 12022.

PW Noble, G Chan, MR Young, RH Weisbart, JE Hansen. Optimizing a lupus autoantibody for targeted cancer therapy. Cancer Res.,  2015, 75(11): 2285-91.

JE Hansen, G Chan, Y Liu, DC Hegan, S Dalal, E Dray, Y Kwon, Y Xu, X Xu, E Peterson-Roth, E Geiger, Y Liu, J Gera, JB Sweasy, P Sung, S Rockwell, RN Nishimura, RH Weisbart, PM Glazer. Targeting cancer with a lupus autoantibody. Sci Transl Med., 2012, 4(157): 157ra142.

Introduction to 3E10

Our platform technology

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