Author: Eagle Biosciences

The MMAE Antibody Drug Conjugate (ADC) ELISA Assay Kit was referenced in a recent publication! Scientists aimed to develop an antibody-drug conjugate (ADDC) to act against MET and RON receptors to treat cancers with high phenotypic heterogeneity. View the abstract and access to the full text below!

Abstract

Cancer heterogeneity, characterized by diverse populations of tumorigenic cells, involves the occurrence of differential phenotypes with variable expressions of receptor tyrosine kinases. Aberrant expressions of mesenchymal–epithelial transition (MET) and recepteur d’origine nantais (RON) receptors contribute to the phenotypic heterogeneity of cancer cells, which poses a major therapeutic challenge. This study aims to develop a dual-targeting antibody–drug conjugate (ADC) that can act against both MET and RON for treating cancers with high phenotypic heterogeneity. Through immunohistochemical staining, we show that MET and RON expressions are highly heterogeneous with differential combinations in more than 40% of pancreatic and triple-negative breast cancer cases. This expressional heterogeneity provides the rationale to target both receptors for cancer therapy. A humanized bispecific monoclonal antibody specific to both MET and RON (PCMbs–MR) is generated through IgG recombination using monoclonal antibody sequences specific to MET and RON, respectively. Monomethyl auristatin E is conjugated to PCMbs–MR to generate a dual-targeting ADC (PCMdt–MMAE), with a drug-to-antibody ratio of 4:1. Various cancer cell lines were used to determine PCMdt-MMAE-mediated biological activities. The efficacy of PCMdt–MMAE in vivo is evaluated using multiple xenograft tumor models. PCMdt–MMAE shows a favorable pharmacokinetic profile, with a maximum tolerated dose of ~30 mg/kg in mice. Toxicological studies using Sprague–Dawley rats reveal that PCMdt–MMAE is relatively safe with slight-to-moderate, temporary, and reversible adverse events. Functionally, PCMdt-MMAE induces a robust internalization of both MET and RON and causes a large-scale cell death in cancer cell lines exhibiting MET and RON heterogeneous co-expressions. Both in vitro and in vivo studies demonstrate that the dual-targeting approach in the form of an ADC is highly effective with a long-lasting effect against tumors exhibiting MET/RON heterogeneous phenotypes. Hence, we can suggest that a dual-targeting ADC specific to both MET and RON can be employed as a novel therapeutic strategy for tumors with expressional phenotypic heterogeneity.

Wang, M., Ma, Q., Suthe, S.R. et al. Humanized dual-targeting antibody–drug conjugates specific to MET and RON receptors as a pharmaceutical strategy for the treatment of cancers exhibiting phenotypic heterogeneity. Acta Pharmacol Sin 46, 1375–1389 (2025). https://doi.org/10.1038/s41401-024-01458-7

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The Calprotectin ELISA Assay Kit was utilized in a recent publication! Researchers investigated whether cytotoxic T-lymphocyte-associated protein 4 deficiency (CTLA4-D), a rare genetic disorder, could be distinguished from an individuals’ microbiome. They also aimed to identify biomarkers to indicate disease severity. Check out the abstract and access to the full text below!

Abstract

Background: Cytotoxic T-lymphocyte-associated protein 4 deficiency (CTLA4-D) is an inborn error of immunity (IEI) caused by heterozygous mutations, and characterized by immune cell infiltration into the gut and other organs, leading to intestinal disease, immune dysregulation and autoimmunity. While regulatory T-cell dysfunction remains central to CTLA4-D immunopathogenesis, mechanisms driving disease severity and intestinal pathology are unknown but likely involve intestinal dysbiosis. We determined whether the intestinal microbiome and metabolome could distinguish individuals with severe CTLA4-D and identify biomarkers of disease severity.

Results: The genera Veillonella and Streptococcus emerged as biomarkers that distinguished CTLA4-D from healthy cohorts from both the National Institutes of Health (NIH) Clinical Center, USA (NIH; CTLA-D, n = 32; healthy controls, n = 16), and a geographically distinct cohort from the Center for Chronic Immunodeficiency (CCI) of the Medical Center – University of Freiburg, Germany (CCI; CTLA4-D, n = 25; healthy controls, n = 24). Since IEIs in general may be associated with perturbations of the microbiota, a disease control cohort of individuals with common variable immunodeficiency (CVID, n = 20) was included to evaluate for a CTLA4-D-specific microbial signature. Despite common IEI-associated microbiome changes, the two bacterial genera retained their specificity as biomarkers for CTLA4-D. We further identified intestinal microbiome and metabolomic signatures that distinguished patients with CTLA4-D having severe vs. mild disease. Microbiome changes were associated with distinct stool metabolomic profiles and predicted changes in metabolic pathways. These differences were impacted by the presence of gastrointestinal manifestations and were partially reversed by treatment with abatacept and/or sirolimus.

Conclusions: Loss of intestinal microbial diversity and dysbiosis causing metabolomic changes was observed in CTLA4-D. Albeit some of these features were shared with CVID, the distinct changes associated with CTLA4-D highlight the fact that IEI-associated microbiome changes likely reflect the underlying immune dysregulation. Identified candidate intestinal microbial and metabolic biomarkers distinguishing individuals with CTLA4-D based on severity should be studied prospectively to determine their predictive value, and investigated as potential therapeutic targets.

Chandrasekaran P, et al. The intestinal microbiome and metabolome discern disease severity in cytotoxic T-lymphocyte-associated protein 4 deficiency. Microbiome. 2025 Feb 11;13(1):51. doi: 10.1186/s40168-025-02028-7. Erratum in: Microbiome. 2025 Mar 15;13(1):74. doi: 10.1186/s40168-025-02069-y. PMID: 39934899; PMCID: PMC11817180.

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The Anti-CCP ELISA Assay Kit played a key role in a new publication! This study aimed to understand pathways leading to B cell activation and autoantibody production, and identify new biomarkers that could be helpful in predicting and assessing the response to abatacept in rheumatoid arthritis patients who don’t respond well to methotrexate and other standard treatments. Dive into the abstract and full paper below!

Abstract

Objectives: To investigate whether biomarkers related to B cell activation and autoantibody production are associated with the response to abatacept in rheumatoid arthritis (RA) patients.

Methods: Twenty-five patients with RA were enrolled in this study. Responders (n=10) to abatacept were subjects who achieved ACR50 response at week 24. Serum levels of soluble biomarkers were measured with ProcartaPlex by Luminex or ELISA. Peripheral blood mononuclear cells were isolated and analysed for T cell and B cell subsets by flow cytometry. Patients were genotyped for human leukocyte antigen (HLA)-DRB1 shared epitope (SE) alleles. Baseline levels and longitudinal changes of markers were assessed between responders and nonresponders.

Results: Baseline levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies (p=0.01), IgM rheumatoid factor (RF) (p=0.02), CXC chemokine ligand 13 (CXCL13, p=0.02), sCD23 (p<0.05), as well as frequencies of CD19+CD11c+IgD-CD27- B cells (p=0.04), were higher in responders than nonresponders. Among them, anti-CCP and frequencies of CD19+CD11c+IgD-CD27- B cells were independently associated with response to abatacept. The presence of two alleles of SE was associated with responders (p=0.04). Patients with 2 alleles of SE had higher levels of anti-CCP (p=0.02) and IgM RF (p=0.04) compared to patients with 0 or 1 allele. Further, IgM RF and CXCL13 levels decreased only in responders (p=0.02 and 0.004 respectively, at week 24), while anti-CCP levels did not decrease significantly in either responders or nonresponders.

Conclusion: Markers of B cell activation including anti-CCP and frequencies of CD19+CD11c+IgD-CD27- B cells in RA were associated with response to abatacept. IgM RF and CXCL13 decreased only in responders and could be potentially used as pharmacodynamic markers.

Wang T, Giltiay NV, Lood C, Wang N and Han BK (2025) Evaluation of B cell related markers and autoantibodies in rheumatoid arthritis patients treated with abatacept. Front. Immunol. 16:1504454. doi: 10.3389/fimmu.2025.1504454

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We’re thrilled to announce that the MedFrontier Intact FGF23 Assay was featured in a recent publication! Details are available via the abstract and full-text access provided below.

Abstract

Multiple myeloma commonly manifests with symptoms arising from the involvement of various organs, particularly the bone and kidneys. In this report, we detail the case of a 44-year-old man who was diagnosed with multiple myeloma associated with reduced bone density. He exhibited clinical findings of osteomalacia due to Fanconi syndrome (characterized clinically by bone pain and proximal weakness and biochemically by elevated serum alkaline phosphatase, hypophosphatemia, hypouricemia, and glucosuria). With phosphate replacement, there was a notable improvement in bone pain, osteomalacia, and bone mineral density. Nevertheless, the patient continued to experience renal wasting of phosphate, uric acid, and glucose despite achieving remission from multiple myeloma for nearly 2 years. Our case highlights several important clinical features of myeloma-associated Fanconi syndrome, including the need to recognize this complication to appropriately treat the underlying bone disease while avoiding osteoclast inhibitors and the long-term persistence of the proximal renal tubulopathy despite achieving remission from myeloma and correction of osteomalacia.

Alireza Zomorodian, Naim M Maalouf, Long-term Evolution of Hypophosphatemia and Osteomalacia in a Patient With Multiple Myeloma, JCEM Case Reports, Volume 2, Issue 7, July 2024, luae137, https://doi.org/10.1210/jcemcr/luae137

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The Niacin Microtiter Plate Assay Kit was utilized in a recent study! Researchers developed a novel approach to study microglia, key immune cells in the CNS, under different conditions. Read on for a summary of this groundbreaking research!

Summary

Microglia are the resident macrophages of the central nervous system (CNS). Their phagocytic activity is central during brain development and homeostasis—and in a plethora of brain pathologies. However, little is known about the composition, dynamics, and function of human microglial phagosomes under homeostatic and pathological conditions. Here, we developed a method for rapid isolation of pure and intact phagosomes from human pluripotent stem cell-derived microglia under various in vitro conditions, and from human brain biopsies, for unbiased multiomic analysis. Phagosome profiling revealed that microglial phagosomes were equipped to sense minute changes in their environment and were highly dynamic. We detected proteins involved in synapse homeostasis, or implicated in brain pathologies, and identified the phagosome as the site where quinolinic acid was stored and metabolized for de novo nicotinamide adenine dinucleotide (NAD+) generation in the cytoplasm. Our findings highlight the central role of phagosomes in microglial functioning in the healthy and diseased brain.

Wogram, E et al. Rapid phagosome isolation enables unbiased multiomic analysis of human microglial phagosomes. Immunity. 57(9)p:2216-2231.e11 doi:10.1016/j.immuni.2024.07.019

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