Antibodies

21 pages, 941 KiB

Open AccessReview

Immunotherapy in GI Cancers: Lessons from Key Trials and Future Clinical Applications

by Supriya Peshin, Faizan Bashir, Naga Anvesh Kodali, Adit Dharia, Sajida Zaiter, Sakshi Singal and Nagaishwarya Moka

Antibodies 2025, 14(3), 58; https://doi.org/10.3390/antib14030058 - 11 Jul 2025

Abstract

Immunotherapy has emerged as a transformative approach in gastrointestinal (GI) cancers, addressing historically poor survival rates in advanced-stage disease. Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis demonstrate remarkable efficacy in colorectal cancer with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H), [...] Read more.

Immunotherapy has emerged as a transformative approach in gastrointestinal (GI) cancers, addressing historically poor survival rates in advanced-stage disease. Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis demonstrate remarkable efficacy in colorectal cancer with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H), exemplified by trials like NICHE-2 achieving exceptional pathological response rates. However, significant limitations persist, including resistance in some dMMR/MSI-H tumors, minimal efficacy in proficient mismatch repair (pMMR) tumors, and low overall response rates across most GI malignancies due to tumor heterogeneity and immune evasion mechanisms. Predictive biomarkers such as tumor mutational burden (TMB) and PD-L1 expression are crucial for optimizing patient selection, while hypermutated pMMR tumors with POLE mutations represent emerging therapeutic opportunities. In pancreatic adenocarcinoma, where survival remains dismal, combination strategies with chemotherapy and novel approaches like cancer vaccines show promise but lack transformative breakthroughs. Esophagogastric cancers benefit from ICIs combined with chemotherapy, particularly in MSI-H and HER2-positive tumors, while hepatocellular carcinoma has achieved significant progress with combinations like atezolizumab–bevacizumab and durvalumab–tremelimumab surpassing traditional therapies. Biliary tract cancers show modest improvements with durvalumab–chemotherapy combinations. Despite these advances, immunotherapy faces substantial challenges including immune-related adverse events, acquired resistance through cancer immunoediting, and the need for biomarker-driven approaches to overcome tumor microenvironment barriers. This review discusses key clinical trials, therapeutic progress, and emerging modalities including CAR T-cell therapies and combination strategies, emphasizing the critical need to address resistance mechanisms and refine precision medicine approaches to fully realize immunotherapy’s potential in GI malignancies. Full article

(This article belongs to the Section Antibody-Based Therapeutics)

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13 pages, 1650 KiB

Open AccessArticle

Isolation of a Monoclonal Human scFv Against Cytomegalovirus pp71 Antigen Using Yeast Display

by Kazuhisa Aoki, Rikio Yabe, Sayaka Ono, Mayumi Saeki, Yuri Tanno and Hidetaka Tanno

Antibodies 2025, 14(3), 57; https://doi.org/10.3390/antib14030057 - 10 Jul 2025

Abstract

Background: Human cytomegalovirus (CMV) is a major pathogen that poses significant risks to immunocompromised individuals and neonates. The tegument protein pp71, encoded by the UL82 gene, plays a pivotal role in initiating viral lytic replication and evading host immune responses. Despite its clinical [...] Read more.

Background: Human cytomegalovirus (CMV) is a major pathogen that poses significant risks to immunocompromised individuals and neonates. The tegument protein pp71, encoded by the UL82 gene, plays a pivotal role in initiating viral lytic replication and evading host immune responses. Despite its clinical relevance, standardized monoclonal antibodies (mAbs) for pp71 remain limited, prompting the need to expand the available repertoire of antibodies targeting this critical protein. Methods: In this study, we constructed a diverse human single-chain variable fragment (scFv) library using RNA derived from the B cells of four healthy donors. The library was expressed in Saccharomyces cerevisiae, and iterative rounds of magnetic-activated cell sorting (MACS) were performed against recombinant pp71. Clonal enrichment was monitored using flow cytometry. Results: Among the isolated clones, one designated ID2 exhibited high sensitivity and specificity for pp71, as demonstrated by flow cytometry, immunofluorescence, an enzyme-linked immunosorbent assay (ELISA), and biolayer interferometry (BLI). Conclusions: Collectively, these findings establish a novel pp71-specific mAb and underscore the utility of yeast surface display combined with MACS for expanding the antibody toolkit available for CMV research and diagnostics. Full article

(This article belongs to the Section Antibody Discovery and Engineering)

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15 pages, 1797 KiB

Open AccessSystematic Review

Diagnosis of Systemic Rheumatic Disease Using the Connective Tissue Disease Screen

by Abeline Kapuczinski, Dorian Parisis, Nour Kassab, Julie Smet and Muhammad Soyfoo

Antibodies 2025, 14(3), 56; https://doi.org/10.3390/antib14030056 - 2 Jul 2025

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Abstract

Connective tissue diseases (CTDs) comprise a heterogeneous group of autoimmune conditions characterized by diverse clinical manifestations and autoantibody profiles, posing significant diagnostic challenges. This systematic review and meta-analysis evaluated the diagnostic performance of automated connective tissue disease screening assays, commonly known as CTD [...] Read more.

Connective tissue diseases (CTDs) comprise a heterogeneous group of autoimmune conditions characterized by diverse clinical manifestations and autoantibody profiles, posing significant diagnostic challenges. This systematic review and meta-analysis evaluated the diagnostic performance of automated connective tissue disease screening assays, commonly known as CTD screens, in diagnosing systemic rheumatic diseases. Eleven studies, including cohort and case–control designs, involving a total of 2384 CTD-positive patients, 8972 controls without CTD, and 679 healthy blood donors, were analyzed. The results demonstrated a pooled sensitivity of 79.36% and specificity of 90.79% for Elia^® CTD-screen, and a sensitivity of 87.23% and specificity of 83.56% for QuantaFlash^® CTD-screen. These tests exhibited varied sensitivity across individual CTDs, with excellent specificity for distinguishing CTD patients from healthy controls. Despite their utility, CTD screens should not be solely relied upon for diagnosis due to limitations in positive predictive value, particularly in low-prevalence populations. Clinical context and expert rheumatological evaluation remain indispensable. Optimizing the use of CTD screens can enhance diagnostic efficiency, reduce unnecessary testing, and mitigate patient anxiety and healthcare costs. Further research focusing on integrating these assays with clinical evaluation is recommended. Full article

(This article belongs to the Section Antibody-Based Diagnostics)

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21 pages, 1316 KiB

Open AccessReview

Teprotumumab for Thyroid Eye Disease: Mechanism, Clinical Efficacy, and Current Challenges

by Yuan Zong, Shuang Qiu, Mingming Yang, Jing Zhang, Yaru Zou, Yuxin Jing, Kyoko Ohno-Matsui and Koju Kamoi

Antibodies 2025, 14(3), 55; https://doi.org/10.3390/antib14030055 - 30 Jun 2025

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Abstract

Thyroid eye disease (TED) is a complex autoimmune disorder characterized by orbital inflammation and tissue remodeling. Teprotumumab, a fully human monoclonal antibody targeting insulin-like growth factor-1 receptor (IGF-1R), represents a significant breakthrough in TED treatment. This review comprehensively analyzes the therapeutic role of [...] Read more.

Thyroid eye disease (TED) is a complex autoimmune disorder characterized by orbital inflammation and tissue remodeling. Teprotumumab, a fully human monoclonal antibody targeting insulin-like growth factor-1 receptor (IGF-1R), represents a significant breakthrough in TED treatment. This review comprehensively analyzes the therapeutic role of teprotumumab in TED management. Mechanistically, teprotumumab inhibits the IGF-1R/TSHR signaling complex, thereby reducing orbital fibroblast differentiation and inflammatory responses. Phase II and III clinical trials have demonstrated its remarkable efficacy in reducing proptosis and improving clinical activity scores, with the benefits extending to both active and chronic TED cases. Real-world studies have validated these findings further and expanded its potential applications to various clinical scenarios, including dysthyroid optic neuropathy and steroid-resistant cases. However, several challenges remain. These include treatment-related adverse effects such as hyperglycemia and hearing impairment, with emerging evidence suggesting ethnic variations in susceptibility. The high cost of treatment poses significant accessibility barriers, while limited long-term follow-up data and potential disease recurrence necessitate further investigation. This review synthesizes the current evidence to inform clinical decision-making and highlights areas requiring additional research to optimize teprotumumab’s therapeutic application in TED management. Full article

(This article belongs to the Section Antibody-Based Therapeutics)

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21 pages, 885 KiB

Open AccessArticle

Survival Outcomes and Prognostic Factors in Rheumatoid Arthritis Patients Receiving Biologic or Targeted Synthetic Therapy: Real-World Data

by Zhaklin Apostolova, Tanya Shivacheva and Tsvetoslav Georgiev

Antibodies 2025, 14(3), 54; https://doi.org/10.3390/antib14030054 - 30 Jun 2025

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Abstract

Objectives: The present study aimed to evaluate the long-term survival of patients with rheumatoid arthritis (RA) receiving biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in a real-world setting, and to identify key prognostic factors influencing mortality within this cohort. Methods: This retrospective, [...] Read more.

Objectives: The present study aimed to evaluate the long-term survival of patients with rheumatoid arthritis (RA) receiving biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in a real-world setting, and to identify key prognostic factors influencing mortality within this cohort. Methods: This retrospective, observational cohort study analyzed 165 patients with confirmed RA who were on b/tsDMARD treatment for at least six months as of June 2017. Patient data, including demographics, disease duration, prior therapeutic regimens, and global functional status were extracted from medical records to collect data covering a seven-year follow-up period, extending from June 2017 to December 2024. Corticosteroid use was defined as continuous systemic intake during the RA activity analysis period. Survival outcomes were analyzed using Kaplan-Meier methods and multivariate Cox proportional hazards models to identify independent predictors of mortality. Results: Over a mean follow-up of 9.4 years, the mortality rate was 13.5 deaths per 1000 treatment-years, with an overall survival rate of 87.3%. Advanced functional disability and prolonged corticosteroid use were independently associated with higher mortality risk. In subgroup analyses, chronic kidney disease significantly increased mortality among patients on TNF inhibitors. In contrast, patients who remained on their initial anti-IL6 therapy had lower mortality, though this may reflect survivor bias. Conclusions: This study highlights the importance of long-term b/tsDMARD intervention in RA patients, with observed low mortality and high survival rates. Subgroup findings suggest the importance of comorbidity management in TNFi users and therapeutic stability in anti-IL6 users. Full article

(This article belongs to the Section Antibody-Based Therapeutics)

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14 pages, 1544 KiB

Open AccessBrief Report

Impact of Light-Chain Variants on the Expression of Therapeutic Monoclonal Antibodies in HEK293 and CHO Cells

by Alexander Veber, Dennis Lenau, Polyniki Gkragkopoulou, David Kornblüh Bauer, Ingo Focken, Wulf Dirk Leuschner, Christian Beil, Sandra Weil, Ercole Rao and Thomas Langer

Antibodies 2025, 14(3), 53; https://doi.org/10.3390/antib14030053 - 24 Jun 2025

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Abstract

Recombinantly produced monoclonal antibodies (mabs) belong to the fastest growing class of biotherapeutics. In humans, antibodies are classified into five different classes: IgA, IgD, IgE, IgG and IgM. Most of the therapeutic mabs used in the clinic belong to the IgG class, albeit [...] Read more.

Recombinantly produced monoclonal antibodies (mabs) belong to the fastest growing class of biotherapeutics. In humans, antibodies are classified into five different classes: IgA, IgD, IgE, IgG and IgM. Most of the therapeutic mabs used in the clinic belong to the IgG class, albeit other antibody classes, e.g., IgM, have been evaluated in clinical stages. Antibodies are composed of heavy chains paired with a light chain. In IgM and IgA, an additional chain, the J-chain, is present. Two types of light chains exist in humans: the κ-light chain and the λ-light chain. The κ-light chain predominates in humans and is used in the vast majority of therapeutic IgG. The reason for the preference of the κ-light chain in humans is not known. Our study investigates whether light-chain selection influences the productivity of the clinically validated mabs adalimumab and trastuzumab. Both mabs were expressed as IgG and IgM with a κ- or a λ-light chain in HEK293 cells. Besides comparing the expression levels of the different mabs, we also evaluated whether the passage number of the cell line has an impact on product yield. In addition, the expressions of adalimumab, trastuzumab, an anti-CD38 and an anti-PD-L1-antibody were analyzed in HEK293 and CHO cells when both the κ- and λ-light chains are present. In summary, IgG outperformed IgM variants in expression efficacy, while light-chain selection had minimal impact on the overall expression levels. The yields of all mab variants were higher in fresh cells, despite cell cultures with a high cell passage number having higher cell densities and cell numbers at the time of harvest. The incorporation of a particular light chain occurred at similar rates in HEK293 and CHO cells. Full article

(This article belongs to the Section Antibody Discovery and Engineering)

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53 pages, 1486 KiB

Open AccessReview

Fragment-Based Immune Cell Engager Antibodies in Treatment of Cancer, Infectious and Autoimmune Diseases: Lessons and Insights from Clinical and Translational Studies

by Ge Yang and Mohammad Massumi

Antibodies 2025, 14(3), 52; https://doi.org/10.3390/antib14030052 - 24 Jun 2025

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Abstract

Since the advent of recombinant DNA technologies and leading up to the clinical approval of T cell engager blinatumomab, the modular design of therapeutic antibodies has enabled the fusion of antibody fragments with proteins of various functionalities. This has resulted in an expansive [...] Read more.

Since the advent of recombinant DNA technologies and leading up to the clinical approval of T cell engager blinatumomab, the modular design of therapeutic antibodies has enabled the fusion of antibody fragments with proteins of various functionalities. This has resulted in an expansive array of possible mechanisms of action and has given birth to fragment-based antibodies (fbAbs) with immune cell engager modalities. In searchable databases, the preclinical development of these antibodies has shown promise; however, clinical outcomes and restructuring efforts involving these agents have produced mixed results and uncertainties. Amid budgetary cuts in both academia and industry, critical planning and evaluation of drug R&D would be more essential than ever before. While many reviews have provided outstanding summaries of preclinical phase fbAbs and cataloged relevant clinical trials, to date, very few of the articles in searchable databases have comprehensively reviewed the details of clinical outcomes along with the underlying reasons or potential explanations for the success and failures of these fbAb drug products. To fill the gap, in this review, we seek to provide the readers with clinically driven insights, accompanied by translational and mechanistic studies, on the current landscape of fragment-based immune cell engager antibodies in treating cancer, infectious, and autoimmune diseases. Full article

(This article belongs to the Special Issue A Festschrift Celebrating Dr. Dimiter Stanchev Dimitrov: Antibodies, Innovation, and Impact on Infectious Disease and Cancer Research)

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Antibodies, Volume 14, Issue 3 (September 2025) – 7 articles

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