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Self-Tumor Antigens in Solid Tumors Turned into Vaccines by α-gal Micelle Immunotherapy.
Pharmaceutics
September 2024
Department of Medicine, Rush University Medical Center, Chicago, IL 60612, USA.
A major reason for the failure of the immune system to detect tumor antigens (TAs) is the insufficient uptake, processing, and presentation of TAs by antigen-presenting cells (APCs). The immunogenicity of TAs in the individual patient can be markedly increased by the in situ targeting of tumor cells for robust uptake by APCs, without the need to identify and characterize the TAs. This is feasible by the intra-tumoral injection of α-gal micelles comprised of glycolipids presenting the carbohydrate-antigen "α-gal epitope" (Galα1-3Galβ1-4GlcNAc-R).
View Article and Find Full Text PDFRegeneration in Mice of Injured Skin, Heart, and Spinal Cord by α-Gal Nanoparticles Recapitulates Regeneration in Amphibians.
Nanomaterials (Basel)
April 2024
Department of Medicine, Rush University Medical Center, Chicago, IL 60612, USA.
The healing of skin wounds, myocardial, and spinal cord injuries in salamander, newt, and axolotl amphibians, and in mouse neonates, results in scar-free regeneration, whereas injuries in adult mice heal by fibrosis and scar formation. Although both types of healing are mediated by macrophages, regeneration in these amphibians and in mouse neonates also involves innate activation of the complement system. These differences suggest that localized complement activation in adult mouse injuries might induce regeneration instead of the default fibrosis and scar formation.
View Article and Find Full Text PDFAccelerated Burn Healing in a Mouse Experimental Model Using α-Gal Nanoparticles.
Bioengineering (Basel)
October 2023
Department of Medicine, Rush University Medical College, Chicago, IL 60612, USA.
Macrophages play a pivotal role in the process of healing burns. One of the major risks in the course of burn healing, in the absence of regenerating epidermis, is infections, which greatly contribute to morbidity and mortality in such patients. Therefore, it is widely agreed that accelerating the recruitment of macrophages into burns may contribute to faster regeneration of the epidermis, thus decreasing the risk of infections.
View Article and Find Full Text PDFAntibody production and tolerance to the α-gal epitope as models for understanding and preventing the immune response to incompatible ABO carbohydrate antigens and for α-gal therapies.
Front Mol Biosci
June 2023
Department of Medicine, Rush University Medical College, Chicago, IL, United States.
This review describes the significance of the α-gal epitope (Galα-3Galβ1-4GlcNAc-R) as the core of human blood-group A and B antigens (A and B antigens), determines in mouse models the principles underlying the immune response to these antigens, and suggests future strategies for the induction of immune tolerance to incompatible A and B antigens in human allografts. Carbohydrate antigens, such as ABO antigens and the α-gal epitope, differ from protein antigens in that they do not interact with T cells, but B cells interacting with them require T-cell help for their activation. The α-gal epitope is the core of both A and B antigens and is the ligand of the natural anti-Gal antibody, which is abundant in all humans.
View Article and Find Full Text PDFGTKO rabbit: A novel animal model for preclinical assessment of decellularized xenogeneic grafts via in situ implantation.
Mater Today Bio
February 2023
Institute for Medical Device Control, National Institutes for Food and Drug Control, Beijing, 102629, China.
Wild type (WT) animals cannot be used to objectively assess the immunogenicity of animal tissue-derived biomaterials when used as recipients due to difference with human in α-Gal expression. The purpose of this study is to compare the differences of immunological responses between the GGTA1 gene-knockout (GTKO) rabbits and WT rabbits after implantation with animal tissue-derived biomaterials. The porcine-derived decellularized bone matrix (natural bone material, NBM) and fresh porcine cancellous bone (PCB) were implanted in GTKO rabbits and WT rabbits, respectively, and sham operation was used as control (Con).
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