Hyperacute Rejection in Transplant
Hyperacute rejection occurs when an organ is mismatched by blood type or, in the case of xenotransplantation, where animal organs are used. The immune system sees such transplants as foreign, triggering pre-existing (“natural”) antibodies to attack, leading to immediate (hyperacute) rejection of the transplanted organ. These antibodies target the non-self or “foreign” glycoantigens (sugars) in the transplanted tissue, including the blood type antigens (ABO), or, in the case of xenotransplantation, the alpha-gal antigen.
XenImmune Proprietary Platform Paints Tumor with Foreign Antigens to Trigger Rejection
XenImmune’s innovative technology causes tumors that were previously unrecognized by the immune system to be flagged as foreign. XenImmune’s novel antibody fusion protein consists of a tumor-specific antibody fused to a glycosyl transferase (GT) enzyme. The antibody portion acts as a guidance system delivering the fusion protein to the tumor cells in the body. Once the fusion protein has bound to the tumor sites, UDP-Gal is added, providing the substrate for the GT enzyme reaction. The GT enzyme transfers the Gal sugar from UDP-Gal to the millions of available glycosylation sites on the tumor cell membranes thereby converting the tumor into non-self/foreign. The immune system responds in a highly robust fashion to reject the cancer, mimicking the response when a mis-matched or foreign organ is transplanted.
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Tumors contain tumor-associated antigens that are specific to cancer cells as well as normal “self” glycosylation sites.
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The Xenimmune targeted antibody-enzyme fusion protein binds to the tumor-associated antigen.
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The Xenimmune targeted antibody-enzyme fusion protein binds to the tumor-associated antigen.
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The subsequent administration of UDP-Gal provides the substrate for the enzymatic reaction, which then coats the tumor with foreign glyco-antigens.
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The tumor, previously unrecognized by the immune system, is now seen by the immune system as if it were a foreign organ, triggering rejection via the existing preformed antibodies in the body.
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The tumor, previously unrecognized by the immune system, is now seen by the immune system as if it were a foreign organ, triggering rejection via the existing preformed antibodies in the body.
Broad Applicability Across Multiple Cancer Types
XenImmune’s modular, proprietary technology platform can be tailored to different solid tumor-specific antigens. We hope to bring the potential of this powerful biology to patients with a range of difficult-to-treat cancers.
Join Our Team
XenImmune is looking for talented scientists and professionals in protein-engineering, immunology, immuno-oncology and drug development. We look forward to hearing from you.