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Research Technology / Antibody Production


Role of Dyslipidemia in Accelerating Inflammation, Autoimmunity, and Atherosclerosis in Systemic Lupus Erythematosus and Other Autoimmune Diseases

Abstract: Dyslipidemia refers to the abnormality of lipid metabolism. The aberrant lipid profiles are usually characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), triglycerides (TGs), apoprotein B (ApoB), and decreased level of high-density lipoprotein cholesterol (HDL-c). Dyslipidemia occurs frequently in autoimmune diseases (ADs), such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type-1 diabetes mellitus (T1DM), psoriasis, and inflammatory bowel disease (IBD), and many other diseases. An imbalance in lipid metabolism contributes to accelerated inflammatory responses in addition to promoting the formation of atherosclerosis. Although there have been many studies and reports on the relationship between abnormal lipid metabolism and ADs, it remains uncertain as to whether dyslipidemia has a unique role in promoting the occurrence and development of ADs. Here, we discuss the mechanisms of how dyslipidemia accelerates inflammatory response, autoimmunity, and atherosclerosis at epidemiological, molecular, and cellular levels, and the discussion is mainly conducted with SLE as an example. ... Read more

All Eyes on the Next Generation of HIV Vaccines: Strategies for Inducing a Broadly Neutralizing Antibody Response

Abstract: HIV-1 broadly neutralizing antibodies (BNAbs) develop after several years of infection through a recursive process of memory B cell adaptation and maturation against co-evolving virus quasispecies. Advances in single-cell sorting and memory B cell antibody cloning methods have identified many new HIV BNAbs targeting conserved epitopes on the HIV envelope (env) protein. 3D crystal structures and biophysical analyses of BNAbs bound to invariant virus structures expressed on monomeric gp120, epitope scaffolds, core structures, and native trimers have helped us to visualize unique binding interactions and paratope orientations that have been instrumental in guiding vaccine design. A paradigm shift in the approach to structure-based design of HIV-1 envelope immunogens came recently after several laboratories discovered that native viral envelopes or "env-structures" reverse-engineered to bind with high affinity to a handful of broadly neutralizing antibodies did not in fact bind the predicted germline precursors of these broadly neutralizing antibodies. A major challenge for HIV-1 B cell vaccine development moving forward is the design of new envelope immunogens that can trigger the selection and expansion of germline precursor and intermediate memory B cells to recapitulate B cell ontogenies associated with the maturation of a broadly neutralizing antibody response. Equally important for vaccine development is the identification of delivery systems, prime-boost strategies, and synergistic adjuvant combinations that can induce the magnitude and quality of antigen-specific T follicular helper (TFH) cell responses needed to drive somatic hypermutation (SHM) and B cell maturation against heterologous primary virus envelopes. Finding the combination of multi-protein envelope immunogens and immunization strategies that can evolve a potent broadly neutralizing antibody response portends to require a complex vaccine regimen that might be difficult to implement on any scale. This perspective strives to integrate recent insights into mechanisms associated with the evolution of an HIV-1 broadly neutralizing antibody response with current immunogen design and proffers a novel immunization strategy for skewing TH17/TFH cell responses that can drive B cell adaptation and affinity maturation associated with a broadly neutralizing antibody response. ... Read more

Novel Immunotherapeutic Approaches to Improve Rates and Outcomes of Transplantation in Sensitized Renal Allograft Recipients

Abstract: Although considerable progress has occurred in kidney transplantation, allograft loss remains a substantial unresolved issue, leading to increased morbidity, mortality, and costs. Preserving, protecting, and extending the functional integrity of allografts is paramount to providing maximal benefits. To this end, identifying critical immunopathologic pathways and biomarkers associated with allograft attrition, with attendant development of rational therapeutic interventions, has emerged as one of the most important objectives of transplant medicine. B-cells and donor-specific anti-HLA antibodies (DSA) are now recognized as important mediators of allograft injury and loss. These findings have led to a renewed interest in therapies that modify B-cells and antibodies. Early experience with desensitization protocols coupled with improved diagnostics for DSAs and renal pathology have greatly improved transplant rates and outcomes for patients once considered at high risk for poor outcomes. Therapies aimed at B-cells and antibodies include high-dose intravenous immunoglobulin (IVIG), plasma exchange (PLEX) with low-dose IVIG, and IVIG combined with rituximab. Developing therapies include proteasome inhibitors aimed at plasma cells, newer monoclonal antibodies that block B-cell growth factors, and modifiers of complement-mediated injury. Here we discuss the importance of B-cells and DSAs as mediators of allograft injury and the evolution of therapies aimed at reducing their impact on allograft survival. ... Read more

The Role of the Epidermal Growth Factor Receptor in the Mechanism and Treatment of Colorectal Cancer

Abstract: The epidermal growth factor receptor is a member of the receptor tyrosine kinase family whose members play a critical role in oncogenesis. In particular, EGFR has been shown to participate in colon cancer development. Due to its role in the progression of colon cancer, EGFR has become an attractive target for therapy and two different classes of biologic agents have been evaluated: the EGFR monoclonal antibodies and the tyrosine kinase inhibitors. These two groups of agents differ in the specific molecular site which they target on the EGFR and in their efficacy in the treatment of colon cancer. This review will discuss the EGFR's evolving role as a prognostic and predictive biomarker in colon cancer. Once thought to be an inherent predictive factor for anti-EGFR monoclonal antibodies (MAbs) the EGFR has been replaced by KRAS and to some extent BRAF. The efficacy of both anti-EGFR MAbs, cetuximab and panitumumab, has been clearly demonstrated to depend upon the KRAS mutational status. The anti-EGFR monoclonal antibodies and their predictive biomarkers have taken colon cancer treatment another step closer towards the goal of tailored cancer therapy. ... Read more

Antibodies in Transplantation

Abstract: Transplantation of cells, tissues, and organs from one individual to another can incite the production of antibodies specific for foreign antigens, especially major histocompatibility antigens, in the graft. Antibodies specific for a graft provide an index of immunity and a potential trigger for injury and rejection. However, the index of immunity can sometimes miss antibody-mediated rejection and besides causing injury the antibodies against a graft can also protect a graft from injury by blocking immune recognition, called enhancement, regulating activation of complement, and inducing changes in the graft that resist damage. Reviewed here are potential limitations in the use of antibodies as an index of immunity and the ways antibodies cause and/or prevent injury. ... Read more

The Immunogenicity of Therapeutic Proteins

Abstract: Nearly all therapeutic proteins induce antibodies in patients. However this immunogenicity has been neglected in the use of these products, even though the antibodies may have severe consequences. During the last few years, progress has been made in understanding why patients do not tolerate these protein therapeutic products and also how to manage the problem of immunogenicity. ... Read more

Green Algae as a Platform to Express Therapeutic Proteins

Abstract: Proteins produced by DNA recombinant technology have been playing important roles in modern medicine ever since the first such protein drug was approved by the U.S. Food and Drug Administration about three decades ago. However the inherent high cost of producing recombinant proteins, particularly those produced from mammalian cells, has hampered their broad application. Other protein expression systems that can reduce the cost yet still maintain the high-level therapeutic activities of the recombinant proteins are a top R&D priority. Eukaryotic unicellular green algae cells may provide a good solution to this long-standing challenge. ... Read more

Intrabodies: Turning the Immune System Inside Out for New Discovery Tools and Therapeutics

Abstract: It is estimated that 63% of drug targets are intracellular and cannot be reached by antibody drugs and many other therapeutic agents. Intrabody (single-chain antibody or its fragments) produced intracellularly is a promising technology that could bring forth intracellular therapeutics in addition to being an important research tool. ... Read more

Intestinal Bacteria and Development of the Antibody Repertoire

Abstract: Mammals have not only allowed a large community of non-pathogenic bacteria to take up residence in their intestinal system, but they also rely on them for their own benefits and development. Intestinal commensal bacteria stimulated the polyclonal expansion of B lymphocytes that produce a diverse and effective antibody repertoire. ... Read more

Rapid Generation of High-level Antibodies in Vitro and in Vivo

Abstract: Therapeutic monoclonal antibodies are currently produced in bioreactors and they require repeated injections during the course of treatment. Patients develop variable levels of antibodies against the monoclonal drugs and reduce or even abolish their effectiveness. In order to avoid this and other side effects, authors produced monoclonal antibodies in vivo by gene transfer technology. The technology could potentially allow patients to make their needed antibody drugs in their own body for handy applications. ... Read more

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