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AGI-134, a fully synthetic α-Gal-based cancer immunotherapy: Synergy with an anti-PD-1 antibody and pre-clinical pharmacokinetic and toxicity profiles.
... As such, rare cell surrogates can be produced in unlimited quantities, and they can be used to screen large numbers of samples [35]. Kodecytes can also be created where xenoantigens are added to human cells [23,36,37]. The laboratory use of xeno-modified human red cells (kodecytes) may soon find uses in monitoring cancer and xenotransplantation therapies. ...
... The ability to activate the complement cascade is a major feature of the potential immuno-oncotherapeutic product based on Kode Technology, which is going into human clinical trials in 2018 [36,37] and is the basis of a method for determining IVIG antibody functionality [24]. ...
Red cells used in immunohaematology are mostly limited to those that nature provides. Very few techniques are available for adding new functionalities to cells, without affecting their intrinsic functionality or vitality. Kode Technology is a surface modification technology that uses amphipathic function-spacer-lipid constructs to rapidly and harmlessly attach bioactive material to cell surfaces (creating kodecytes) and nonbiological surfaces (koded surfaces). Originally designed to attach blood group glycans onto red blood cells for quality control use, the technology has since expanded to modification of any type of cell, enveloped virus, liposome and nonbiological surfaces (including plastics, metals and glass). Today, Kode Technology and the resultant kodecytes are being used in a range of cell-based diagnostics, as powerful research tools, and most recently as a potential immuno-oncotherapeutic agent; soon to enter human trials. Immunohaematology applications and opportunities to use the technology in the form of kodecytes range from quality control kits, competency training panels, diagnostic reagents with synthetic rare blood group antigens or infectious disease markers. The constructs can be used for solid-phase antibody mapping and also have potential as therapeutics, including in vivo neutralization of ABO antibodies. Together with a large range of R&D constructs, Kode Technology remains the most extensive and easy-to-use technology for adding bioactive material onto the surface of cells for research and diagnostics.
... The complement activating ability of kodecytes is a major feature of the potential immuno-oncotherapeutic product AGI-134 based on Kode Technology (Middleton et al. 2017;Kristian et al. 2016). The concept for this immunotherapy was developed by Uri Galili where he used glycolipids isolated from rabbit red cells as the source of glycan linear B xeno antigens for inserting into cell membranes (Abdel-Motal et al. 2009;Galili 2013). ...
Cells are highly decorated with glycans (carbohydrates) and this complex and dominating coating on cells, which also carries the glycan blood group antigens, is critically important to immunology and many related clinical practices such as transfusion, transplantation and immunotherapy. The ability to modify this glycan coat is difficult to achieve with standard techniques like molecular biology or direct chemical ligation, particularly as glycosylation is probably the most complex secondary gene event in a cell. However, the natural ability of lipid-linked structures to self-insert and hydrophobically anchor into cell membranes opened up the opportunity to develop synthetic Function-Spacer-Lipid technology for cell surface modification. From this glycan modification aspect Kode Technology has been used to add glycan related blood group antigens such as ABO, Lewis, P, FORS, as well as sialo-oligosaccharides and hyaluronic acid onto cells to study immunology and cell glycosylation and more recently as a potential immuno-oncotherapeutic therapy.
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