Antibodies最新文献

Paraneoplastic pemphigus (PNP) is a rare autoimmune disorder associated with underlying neoplasms, predominantly Non-Hodgkin Lymphomas, affecting adults aged 45 to 70. This review analyzed 87 articles from MEDLINE/PubMed, Ovid and Scopus focusing on patients with oral manifestations of PNP, emphasizing histological and serological aspects and discussing recent updates on pathogenetic options. Key findings revealed that PNP is often diagnosed before the neoplasm, with Follicular variant Non-Hodgkin Lymphoma and Castleman Disease being the most common associations. Histopathological analysis showed suprabasal acantholysis and inflammation, and serological tests identify a comprehensive autoantibody panel, underscoring the need for standardized diagnostic criteria and improved serological testing.

Background: Although immune checkpoint inhibitors (ICIs) have demonstrated efficacy in treating advanced cancers, their therapeutic success remains limited for many patients, with initial responders often experiencing resistance and relapse. Interleukin-12 (IL-12) is a powerful cytokine for antitumor immunotherapy, enhancing both lymphocyte recruitment into tumors and immune cell activation. Methods: In this study, we successfully produced mouse interleukin-12 (mIL12) through eukaryotic recombinant expression. In vivo, mIL12 exhibited significant control of tumor immunity in ICI-resistant and aggressive tumor models. Further mechanistic analysis indicated that treatment with mIL12 led to a substantial increase in tumor-infiltrating CD4⁺ T, CD8⁺ T, cDC1, and CD103⁺ cDC1 cells. Results: Our data underscore the potential of a combined therapeutic strategy involving IL-12 with PD-1 and CTLA-4 blockade to elicit a potent antitumor immune response. Notably, the co-administration of mIL12 and PD-1 blockade significantly enhanced the presence of central memory T cells (T_CM) within tumors. Conclusions: This study is the first to provide evidence that the combination of mIL12 and PD-1 blockers promotes the generation of T_CM, potentially contributing to a robust and durable antitumor effect.

Immuno-oncology has revolutionized cancer treatment, with NKG2A emerging as a novel target for immunotherapy. The blockade of NKG2A using the immune checkpoint inhibitor (ICI) monalizumab has been shown to enhance the responses of both NK cells and CD8+ T cells. However, monalizumab has demonstrated limited efficacy in in vitro cytotoxic assays and clinical trials. In our study, we discovered and characterized a novel anti-NKG2A antibody, BRY805, which exhibits high specificity for the human CD94/NKG2A heterodimer complex and does not bind to the activating NKG2C receptor. In vitro cytotoxicity assays demonstrated that BRY805 effectively activated NK92 cells and primary NK cells, thereby enhancing the cytotoxic activity of effector cells against cancer cells overexpressing HLA-E, with significantly greater efficacy compared to monalizumab. Furthermore, BRY805 exhibited synergistic antitumor activity when combined with PD-L1 monoclonal antibodies. In a mouse xenograft model, BRY805 showed superior tumor control relative to monalizumab and demonstrated a favorable safety profile in non-human primate studies.

Background/objectives: Schizophrenia (SZ) is a complex psychiatric disorder with increasing evidence pointing to an autoimmune component, including the presence of antiphospholipid antibodies (aPLs). This study aims to assess the prevalence of anticardiolipin (aCL) and anti-beta-2 glycoprotein I (aβ2GPI) antibodies, particularly the IgG, IgA, and IgM isotypes, in drug-free SZ patients compared to healthy controls, and explore their possible involvement in the disease's pathophysiology.

Methods: Eighty SZ patients meeting DSM-IV criteria were recruited, along with 80 matched healthy controls. Serum samples were analyzed using enzyme-linked immunosorbent assays (ELISA) to quantify IgG, IgA, and IgM isotypes of aCL and aβ2GPI.

Results: SZ patients exhibited significantly higher levels of aCL-IgM and aCL-IgA (p < 0.05), as well as elevated aβ2GPI-IgA (22.5%, p < 0.001), compared to controls. No significant differences were observed in the aCL-IgG isotype. Interestingly, 72% of aPL-positive SZ patients were positive for aβ2GPI-IgA, with some also co-expressing multiple isotypes, suggesting a potential link between SZ and antiphospholipid syndrome (APS).

Conclusions: This study is the first to report a high prevalence of aCL-IgA and aβ2GPI-IgA in SZ patients, highlighting a possible autoimmune involvement in the disease. The presence of multiple aPL isotypes, particularly IgA, suggests a need for further investigation into their role in SZ pathogenesis and their potential association with APS.

Background: Ocular predominant mucous membrane pemphigoid (oMMP) is a severe subtype of autoimmune blistering disease (AIBD), which can result in scarring and vision loss. The diagnosis of oMMP is challenging as patients often have undetectable levels of circulating autoantibodies by conventional assays. Likewise, the principal autoantigen in oMMP has been an area of debate. Methods: In this preliminary experiment, we performed Phage Immunoprecipitation Sequencing (PhIP-seq) on sera from patients with oMMP, as well as non-ocular MMP, bullous pemphigoid, and mucocutaneous-type pemphigus vulgaris. Results: We identified several autoantigens unique to oMMP relative to other AIBDs. We then cross-referenced these antigens against previously published single-nuclei datasets, as well as the International Mouse Phenotyping Consortium Database. Several protein hits identified in our study demonstrated enriched expression on the anterior surface epithelia, including TNKS1BP1, SEC16B, FNBP4, CASZ1, GOLGB1, DOT1L, PRDM 15, LARP4B, and RPL6. Likewise, a previous study of mouse knockout models of murine analogs CASZ1, HIP1, and ELOA2 reported that these mice showed abnormalities in terms of the ocular surface and development in the eyes. Notably, PhIP-seq failed to identify the canonical markers of AIBDs such as BP180, BP230, desmogleins 1 and 3, or integrin β4, indicating that the patient autoantibodies react with conformational epitopes rather than linear epitopes. Conclusions: oMMP patients demonstrate a unique autoantibody repertoire relative to the other AIBDs. Further validation of the identified autoantibodies will shed light on their potentially pathogenic role.

This review briefly traces the historical development of antibody research and related technologies. The path from early perceptions of immunity to the emergence of modern immunotherapy has been marked by pivotal discoveries and technological advances. Early insights into immunity led to the development of vaccination and serotherapy. The elucidation of antibody structure and function paved the way for monoclonal antibody technology and its application in diagnosis and therapy. Breakthroughs in genetic engineering have enabled the production of humanized antibodies and the advances in Fc engineering, thereby increasing therapeutic efficacy. The discovery of immune checkpoints and cytokines revolutionized the treatment of cancer and autoimmune diseases. The field continues to evolve rapidly with the advent of antibody-drug conjugates, bispecific antibodies, and CAR T-cell therapies. As we face global health challenges, antibody research remains at the forefront of medical innovation and offers promising solutions for the future.

When developing immunochemical test systems, it is necessary to obtain specific antibodies. Their quality depends, among other things, on the immunogen used. When preparing hapten-protein conjugates to obtain antibodies for low-molecular-weight compounds, the key factors are the structure of the hapten itself, the presence of a spacer, the size of the carrier protein and the degree of its modification by hapten molecules. This work shows that one additional factor-the conditions for obtaining the hapten-protein conjugate-is overlooked. In this work, we have synthesized conjugates of bisphenol A derivative 4,4-bis(hydroxyphenyl)valeric acid (BVA), the protein carrier soybean trypsin inhibitor (STI), and bovine serum albumin (BSA) in reaction media combining water with two organic solvents: dimethylformamide (DMF) or dimethyl sulfoxide (DMSO). Namely, BSA_DMF-BVA, STI_DMF-BVA, BSA_DMSO-BVA and STI_DMSO-BVA conjugates were obtained. Rabbit polyclonal antibodies against the BSA_DMF-BVA conjugate demonstrated basically different interactions in the developed ELISA systems using either STI_DMF-BVA or STI_DMSO-BVA conjugates. The use of the STI_DMF-BVA conjugate demonstrated the absence of competition in combination with antisera obtained from BSA_DMF-BVA in an ELISA. A competitive interaction was observed only with the use of the STI_DMSO-BVA conjugate. Under the selected conditions, the detection limit of bisphenol A was 8.3 ng/mL, and the working range of determined concentrations was 18.5-290.3 ng/mL. The obtained data demonstrate the possibility of achieving sensitive immunoassays by simply varying the reaction media for the hapten-protein conjugation, which could provide an additional tool in the development of immunoassays for other low-molecular-weight compounds.

Background/Objectives: Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally, though advances in targeted therapies have improved treatment outcomes. The mesenchymal-epithelial transition (MET) gene plays a significant role in NSCLC, often through protein overexpression, exon 14 skipping mutations, and gene amplification, many of which arise as resistance mechanisms to other oncogenic drivers like epidermal growth factor receptor (EGFR) mutations. This review examines the development and clinical efficacy of anti-MET antibody therapies. Methods: A comprehensive literature search was conducted using major medical databases looking at key relevant studies on anti-MET antibody studies. Both authors reviewed the literature, assessed study quality, and interpreted the results from each study. Results: Amivantamab, a bispecific EGFR/MET antibody was approved to treat EGFR exon 20 insertion and now has recently been extended to target classical EGFR mutations with progression on osimertinib. Other important anti-MET targeted therapies in development include antibody drug conjugates such as telisotuzumab vedotin, REGN5093-M114, and AZD9592 and emibetuzumab, which is a humanized immunoglobulin G4 monoclonal bivalent MET antibody. Conclusions: MET plays a significant role in NSCLC and amivantamab along with other anti-MET targeted therapies play a role in directly targeting MET and addressing acquired resistance to oncogenic drivers. Future research should focus on developing novel MET antibody drugs and exploring new therapeutic combinations to enhance treatment efficacy and overcome resistance in NSCLC. Refining biomarker-driven approaches to ensure precise patient selection is also critical to optimizing treatment outcomes.

Background: Autoantibodies are commonly used as biomarkers in autoimmune diseases, but there are limitations. For example, autoantibody biomarkers have poor sensitivity or specificity in systemic lupus erythematosus and do not exist in the spondyloarthropathies, impairing diagnosis and treatment. While autoantibodies suitable for strong biomarkers may not exist in these conditions, another possibility is that technology has limited their discovery. The purpose of this study was to use a novel high-density peptide array that enables the evaluation of IgG binding to every possible linear antigen in the entire human peptidome, as well as a novel machine learning approach that incorporates ELISA validation predictability in order to discover autoantibodies that could be developed into sensitive and specific markers of lupus or spondyloarthropathy.

Methods: We used a peptide array containing the human peptidome, several viral peptidomes, and key post-translational modifications (6 million peptides) to quantify IgG binding in lupus, spondyloarthropathy, rheumatoid arthritis, Sjögren's disease, and control sera. Using ELISA data for 70 peptides, we performed a random forest analysis that evaluated multiple array features to predict which peptides might be good biomarkers, as confirmed by ELISA. We validated the peptide prediction methodology in rheumatoid arthritis and COVID-19, conditions for which the antibody repertoire is well-understood, and then evaluated IgG binding by ELISA to peptides that we predicted would be highly bound specifically in lupus or spondyloarthropathy.

Results: Our methodology performed well in validation studies, but peptides predicted to be highly and specifically bound in lupus or spondyloarthropathy could not be confirmed by ELISA.

Conclusions: In a comprehensive evaluation of the entire human peptidome, highly sensitive and specific IgG autoantibodies were not identified in lupus or spondyloarthropathy. Thus, the pathogenesis of lupus and spondyloarthropathy may not depend upon unique autoantigens, and other types of molecules should be sought as optimal biomarkers in these conditions.

Background: Monoclonal antibodies (mAbs) have demonstrated substantial potential in the treatment of intraocular diseases. This review aimed to comprehensively evaluate the applications, efficacy, and safety of mAbs in the management of intraocular conditions.

Methods: A comprehensive literature search was conducted in major medical databases through July 2024. Relevant studies on monoclonal antibodies for intraocular diseases were included. Two independent researchers screened the literature, extracted data, and assessed study quality. Cost-effectiveness analyses were also reviewed.

Results: Anti-vascular endothelial growth factor (VEGF) antibodies, such as bevacizumab, ranibizumab, and aflibercept, showed significant therapeutic effects in neovascular age-related macular degeneration (NVAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Tumor necrosis factor-alpha (TNF-α) inhibitors demonstrated promising results in treating noninfectious uveitis. Complement system-targeted therapies like pegcetacoplan offered new options for geographic atrophy. Anti-VEGF antibodies showed potential in managing retinopathy of prematurity (ROP). However, challenges persist, including high costs, potential drug resistance, and limited long-term safety data in certain scenarios.

Conclusions: Monoclonal antibodies are vital for treating intraocular diseases, but continuous innovation and rigorous clinical evaluation are essential. Future research should focus on developing novel delivery systems, exploring combination therapies, conducting long-term follow-up studies, and investigating personalized treatment strategies to provide safer, more effective, and cost-effective therapeutic solutions.