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Deoxymabs

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Deoxymab antibodies exhibit several distinctive properties ideal for human therapeutic applications, including DNA targeting, blood-brain barrier penetration and inhibition of the inflammatory process NETosis. These unusual properties have opened up a range of therapeutic approaches. Currently, a collaboration with Monash University is assessing the impact of the deoxymabs PAT-DX1 and PAT-DX3 on vasculitis.

PAT-DX3 is a humanised, full-sized antibody, that has been further optimised to improve its therapeutic potential. PAT-DX3 is likely to have clinical utility for treating primary and secondary brain cancers due to its ability to cross the blood brain barrier. It may also have utility for treating cancers and/or metastases that are associated with NETosis, or in combination with DNA damaging agents such as radiation and many chemotherapy drugs.

PAT-DX3 is expected to have different pharmaceutic properties (tissue distribution, pharmacokinetic profile etc) to PAT-DX1 due to its larger size.

PAT-DX1 is a dimer of a small antibody fragment derived from a humanised version of the binding domain from the original mouse deoxymab antibody 3E10. Patrys has manufactured a large scale GMP batch of PAT-DX1 and is seeking strategic partnerships for its co-development and licensing.

Fei Cao, Caroline Tang, Xiaoyong Chen, Zewei Tu, Ying Jin, Olivia M. Turk, Robert N. Nishimura, Allen Ebens, Valentina Dubljevic, James A. Campbell, Jiangbing Zhou, and James E. Hansen. Cathepsin B Nuclear Flux in a DNA-Guided “Antinuclear Missile” Cancer Therapy ACS Central Science 

 (8), 1562-1572 DOI: 10.1021/acscentsci.4c00559


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.


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.

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.

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.