The secretory immunoglobulin A (SIgA) is the predominant antibody in mucosal surfaces, playing a crucial role in immune defense by interacting with both commensal and...
The secretory immunoglobulin A (SIgA) is the predominant antibody in mucosal surfaces, playing a crucial role in immune defense by interacting with both commensal and pathogenic microbes. The secretory component (SC) is a part of SIgA as well as SIgM (secretory IgM), and facilitates the binding of polymeric IgA and IgM to epithelial cells, allowing their transcytosis and secretion into the lumen. The SC also enhances the stability of SIg by protecting them from proteolytic degradation, aids in their localization in the mucus layer, promotes intralumenal sequestration of bacteria, and performs homeostatic functions in the epithelium.
This technology is a chimeric secretory immunoglobulin A (cSIgA) where the secretory component (SC) is replaced with a single domain antibody. This bispecific cSIgA can bind its target antigen and additional ligands by the engineered SC portion, such as toxins or surface antigens. This can be applied to treatment for mucosal infections such as Clostridium difficile. Compared to unmodified SIgA, cSlgA exhibits increased neutralization potency against C. difficile toxins, promotes bacterial clumping and cell rupture, and has decreased cytotoxicity.
Benefits Bispecific cSIgA binds its target antigen and additional ligands (e.g., toxins or surface antigens)
Applications Anti-infective, Diagnostics, Research Tool
Publication Engineered Secretory Immunoglobulin A provides insights on antibody-based effector mechanisms targeting Clostridiodes difficile Sonya Kumar Bharathkar, Michael J. Miller, Beth M. Stadtmueller bioRxiv 2023.11.08.566291; doi: https://doi.org/10.1101/2023.11.08.566291
Exosomes are nano-sized vesicles secreted by cells that contain proteins, RNAs, polysaccharides, and lipids, playing a key role in cellular communication and holding...
Exosomes are nano-sized vesicles secreted by cells that contain proteins, RNAs, polysaccharides, and lipids, playing a key role in cellular communication and holding promise for diagnostic and therapeutic applications. Tumor-derived exosomes facilitate tumor progression and metastasis by transporting molecular messages and contribute to the immunosuppressive tumor microenvironment. They can penetrate blood vessels and circulate in the bloodstream, making them potential markers for cancer diagnosis. Exosomes also serve as a source of tumor antigens for cancer vaccines, which aim to generate antigen-specific immune responses. However, identifying tumor-specific antigens is complex and costly. Tumor exosome-based vaccines have shown promise in clinical trials but face challenges in effectively activating dendritic cells (DCs) and generating strong cytotoxic T lymphocyte (CTL) responses. The integration of adjuvants with tumor exosomes has not significantly improved vaccine potency due to differing trafficking and uptake profiles. There is a need for effective methods to conjugate adjuvants to exosomes to enhance their synergistic effects.
This technology is a method for development of personalized cancer vaccines using cancer cell-derived exosomes. Cancer cells collected from a patient can be labeled with unnatural sugars displaying the azide functional group. Exosomes generated from these cancer cells can be conjugated to adjuvants (or other tags or fluorescent dyes for diagnostic or research purposes) via click chemistry and reintroduced into the patient. Components of the exosome can be recognized as antigens and help the immune system in producing antigen-specific T cells and antibodies, showing a lower concentration of adjuvant is required to trigger the immune response.
Benefits
Conjugating adjuvant to exosomes improves immune response against cancer cells.
Lower concentration of potentially toxic adjuvant is required to trigger the immune response.
Publication Bhatta, R., Han, J., Liu, Y. et al. Metabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines. Nat Commun 14, 8047 (2023). https://doi.org/10.1038/s41467-023-43914-8
Amyotrophic lateral sclerosis (ALS) is a fatal neurogenerative disorders that affect 5,000 people in the U.S. each year. Huntington’s disease (HD) is another progressive...
Amyotrophic lateral sclerosis (ALS) is a fatal neurogenerative disorders that affect 5,000 people in the U.S. each year. Huntington’s disease (HD) is another progressive and fatal neurogenerative disorder that affects nearly 30,000 people in the U.S. Both of these neurodegenerative disorders are associated with abnormal protein accumulation, such as SOD1 and HTT. CRISPR-Cas13 targets the genes of interest (i.e., SOD1 and HTT) and ultimately reduces the gene expression that are related to ALS and HD. Previous CRISPR technologies often use the Cas9 enzyme, which presents multiple problems with ease of delivery, size, and potential genomic damage to cells. Cas13 is smaller in size, making it easier to deliver. Furthermore, Cas13 targets the RNA—not the DNA, which means Cas13 downregulates gene expression without having to change the DNA sequence.
Therapeutic antibodies are widely used in biotherapeutics due to their unique antigen specificity and versatility against various disease targets. There is growing...
Therapeutic antibodies are widely used in biotherapeutics due to their unique antigen specificity and versatility against various disease targets. There is growing interest in using antibody fragments as therapeutics because their small size allows for better tumor penetration and cost-effective production. However, their small size also leads to rapid clearance (7-20 hours in humans), reducing their efficacy. Therefore, there is a need for new compositions and methods to overcome these limitations and enhance the effectiveness of small antibody therapeutics.
This technology is a method to extend the circulation half-life of antibody fragments. This approach is based on novel short peptides that mimic the functionality of FcRn binding domains (allowing transcytosis and recycling) without significantly increasing the size of the antibody fragment. Extending the half-life of antibody fragments from hours to weeks increases their theaputic potential in cancer treatment.
Publication
Short FcRn-Binding Peptides Enable Salvage and Transcytosis of scFv Antibody Fragments. Vince W. Kelly and Shannon J. Sirk. ACS Chemical Biology 2022 17 (2), 404-413 DOI: 10.1021/acschembio.1c00862
Antibodies serve as both therapeutic and research tools due to their high specificity and low immunogenicity. Therapeutically, they target specific antigens to treat...
Antibodies serve as both therapeutic and research tools due to their high specificity and low immunogenicity. Therapeutically, they target specific antigens to treat diseases like cancer and diabetes. In research, they aid in protein localization, isolation, and cell separation. Their reproducibility and scalability make them valuable, but the need for diverse antibodies necessitates ongoing discovery and testing. Limiting focus to human antibodies restricts availability, while chimeric and humanized antibodies expand the range to include non-naturally occurring types, enhancing their application and functionality.
This technology is a chimeric antibody engineered by joining immunoglobulin M (IgM) fragments from humans and teleost fish, which does not encode a Joining-Chain (JC) to assemble polymeric immunoglobulins. The resulting structure is distinct from mammalian IgM. Receptor binding sections of the chimeric antibody are from the human sequences, and therefore they react with human antigens. This undiscovered chimeric class of human tetrameric antibodies widen the variety and potential applications of antibodies for therapeutic and research purposes.
Type 1 diabetes--when a human's body is unable to produce sufficient insulin to regulate blood sugar levels--impacts millions of people worldwide, including nearly 2...
Type 1 diabetes--when a human's body is unable to produce sufficient insulin to regulate blood sugar levels--impacts millions of people worldwide, including nearly 2 million people in the US alone. The advent of insulin injections a centuray ago to treat type 1 diabetics transformed the disease from a virtual death sentence to a manageable medical condition. More than 100 years after the first treatment of a type 1 diabetic with insulin, however, people suffering from type 1 diabetes still must administer daily injections in order to manage their disease.
Minimally-invasive, long-term blood sugar control would transform the lives of people suffering from Type I diabetes, who currently manage their disease through constant insulin monitoring, a specialized diet, and daily injections. Researchers from the University of Illinois Urbana-Champaign have developed a technology that enables such treatment. Their approach uses a system of microcapsules and microspheres to introduce and sustain insulin-producing porcine pancreatic islets within a patient for weeks or more.
Benefits
Long-term blood sugar control
Could reduce or eliminate need for insulin injections
