Antibodies最新文献

{"title":"B Cells and Tumor Immunometabolism: Emerging Insights into Immune Regulation and Therapeutic Resistance.","authors":"Swati Gupta, Sandip Rath, Surathi Maiti, Tapas Das, Farhat Afrin","doi":"10.3390/antib15050087","DOIUrl":"10.3390/antib15050087","url":null,"abstract":"<p><p>Cancer progression and therapeutic resistance are shaped by reciprocal dynamic interactions between malignant cells and the metabolically altered tumor microenvironment (TME). Tumor-associated hypoxia, glucose and amino acid competition, extracellular acidity, lactate accumulation, adenosine, prostaglandin E2 (PGE2) and other metabolic signals can remodel immune cell function and determine whether inflammation is tumoricidal or tumor-supportive. Although B lymphocytes have traditionally been viewed as antibody-producing cells, tumor-infiltrating B (TIL-B) cells comprise functionally heterogeneous populations that can act as antigen-presenting cells, cytokine and chemokine producers, antibody-secreting cells, cytotoxic effectors, regulatory B cells (Bregs) and organizers of tertiary lymphoid structures (TLSs). Their functional state is strongly influenced by the metabolic and spatial context in which they reside. This review focuses on the intersection of B cell biology and tumor immunometabolism, emphasizing how hypoxia, lactate, nutrient limitation, adenosine, PGE2, kynurenine and B cell-derived γ-aminobutyric acid (GABA) may shape B cell states and their interactions with myeloid and lymphoid cells. We discuss how metabolically conditioned Bregs and immunoglobulin (Ig)A-skewed humoral responses can contribute to immune suppression, whereas metabolically competent antigen-presenting, IgG-biased and TLS-associated B cell responses may support effective anti-tumor immunity. Importantly, the effects are tumor type- and context-dependent: B cell/TLS signatures are associated with favorable outcomes in several breast, lung and other solid tumors, whereas B cell-centered immune landscapes can be suppressed or neutral in pancreatic cancer and IgA-dominated responses may be unfavorable in selected malignancies. We further examine how these states may influence sensitivity or resistance to immune checkpoint blockade, chemotherapy, radiotherapy and cellular therapies. Finally, we highlight B cell metabolic pathways as potential therapeutic entry points and identify priorities for spatial metabolomics and prospective interventional studies.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Therapy for Antihistamine-Refractory Chronic Spontaneous Urticaria: A Critical Narrative Review and an Evidence-Graded Approach to Agent Selection.","authors":"Luca Guarino, Giuseppe Rizzuto, Vincenzo Coppolelli, Alessia Scipione, Mirella Scattone, Luca Gargano, Pietro Scribani Rossi, Ester Del Duca, Annunziata Dattola, Giovanni Pellacani, Steven Nisticò, Camilla Chello","doi":"10.3390/antib15050088","DOIUrl":"10.3390/antib15050088","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Chronic spontaneous urticaria (CSU) is a mast-cell-driven disease with autoimmune mechanisms and an incompletely clarified aetiology, in which a substantial proportion of patients remain symptomatic despite second-generation H1-antihistamines; until recently, omalizumab was effectively the only targeted option, leaving a considerable non-responder fraction. Between February 2024 and September 2025 the landscape changed: dupilumab (anti-IL-4Rα) and the first oral Bruton tyrosine kinase (BTK) inhibitor, remibrutinib, were approved for CSU; omalizumab biosimilars reached the market; the higher-affinity anti-IgE antibody ligelizumab was discontinued; and the investigational anti-KIT antibody barzolvolimab advanced to phase 3-creating new therapeutic opportunities for non-responders while leaving the choice among these second-line options unresolved by current guidelines. We provide a critical synthesis and propose an evidence-graded process for agent selection, together with a proposed repositioning of the available agents, taking the 2022 EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline as the acknowledged reference. <b>Methods:</b> Critical narrative review with a structured but non-systematic search (PubMed, ClinicalTrials.gov) and a pre-specified evidence hierarchy (guideline to expert opinion); each clinical claim is annotated by its level of evidence. <b>Results:</b> Four agents are appraised in turn-omalizumab (anti-IgE, first-line), dupilumab (anti-IL-4Rα), remibrutinib (oral BTK inhibitor, small-molecule comparator) and barzolvolimab (anti-KIT, investigational). Current evidence appears to support omalizumab as first-line, with mechanism-guided second-line choices conditioned on endotype, comorbidity, prior biologic exposure and safety. <b>Conclusions:</b> The complexity of CSU and the incomplete response to currently available therapies support a patient-tailored approach to treatment selection.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody-Based Biologics for CNS Disorders.","authors":"Eric Ka-Wai Hui, Ruben J Boado","doi":"10.3390/antib15050086","DOIUrl":"10.3390/antib15050086","url":null,"abstract":"<p><p>The blood-brain barrier (BBB) is permeable only to small lipophilic molecules, whereas hydrophilic nutrients, such as glucose and amino acids, cross the BBB via carrier-mediated transport systems. In contrast, circulating proteins do not cross the BBB. However, the BBB expresses receptors able to induce receptor-mediated transcytosis (RMT) of selective proteins across the BBB, as in the case of insulin, transferrin, and insulin-like growth factor 1 (IGF1). This led to the hypothesis that the transport of protein-based biologics to the brain may be possible by targeting BBB receptors that induce RMT. Monoclonal antibodies targeting these receptors penetrate the BBB via RMT and are distributed throughout the brain, acting as molecular Trojan horses and/or shuttle systems. A generation of brain-penetrating fusion proteins was produced targeting BBB insulin, transferrin, and IGF1 receptors, respectively, with full antibodies and/or antibody fragments acting as transport domains. These antibody-based fusion proteins were validated in various experimental models, including lysosomal storage disorders (LSDs), stroke, Parkinson's disease, and Alzheimer's disease (AD), respectively. Clinical trials with brain-penetrating antibody-based biologicals targeting BBB transferrin and insulin receptors have been completed or are in progress in LSDs and in AD. The aim of this review is to examine the progress made in antibody-based biologicals for CNS disorders from genetic engineering to clinical trials.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Clinical Associations of Systemic Sclerosis-Related Autoantibodies: A Nationwide Reuma.pt Cohort Study.","authors":"Carolina Mazeda, Eduardo Dourado, Raquel Freitas, Patrícia Martins, Liliana Saraiva, Tânia Santiago, Francisca Guimarães, Emanuel Costa, Diogo Esperança Almeida, Sara Dinis, Ana Sofia Pinto, Alexandra Daniel, Inês Genrinho, Maura Couto, Marília Rodrigues, Maria João Salvador, Ana Catarina Duarte, Ana Cordeiro, Maria José Santos, João Eurico Fonseca, Catarina Resende, Inês Cordeiro","doi":"10.3390/antib15050085","DOIUrl":"10.3390/antib15050085","url":null,"abstract":"<p><p><b>Background:</b> Autoantibodies are central to the diagnosis and risk stratification of systemic sclerosis (SSc), but their prevalence and clinical associations may vary across populations. This study aimed to evaluate the prevalence and immuno-clinical associations of different autoantibodies in the Rheumatic Diseases Portuguese Register systemic sclerosis cohort. <b>Methods:</b> This was a multicentre observational registry-based study that used data from the Reuma.pt SSc module. Patients were divided according to autoantibody status, and associations between autoantibody expression and clinical data were assessed using appropriate statistical tests, with Bonferroni correction applied for multiple comparisons. Multivariable binary logistic regression was performed for clinically relevant outcomes, with adjustment for sex, age at diagnosis and disease duration. <b>Results:</b> A total of 1080 patients were included, 87.5% female, with a mean age at last evaluation of 60.2 ± 14.6 years and a mean disease duration of 12.4 ± 10.0 years. Limited cutaneous SSc was the most frequent clinical category (57.4%), followed by diffuse cutaneous SSc (17.7%), very early diagnosis of systemic sclerosis (VEDOSS; 12.3%), overlap syndromes (9.8%) and SSc sine scleroderma (2.8%). Antinuclear antibodies were present in 93.4% of patients. Anti-centromere antibodies (ACAs) were the most frequent SSc-specific autoantibodies (54.6%), followed by topoisomerase I antibodies (ATAs; 21.8%). ACA positivity was associated with limited cutaneous disease; older age at diagnosis; and lower frequency of interstitial lung disease (ILD), myositis and flexion contractures. ATA positivity was associated with diffuse cutaneous disease, male sex, higher modified Rodnan skin score (mRSS), digital ulcers, flexion contractures, oesophageal involvement and ILD. Among less frequent autoantibodies, anti-Pm/Scl antibodies were associated with myositis, joint involvement, calcinosis and ILD; anti-U1RNP antibodies with younger age, MCTD overlap, myositis and joint involvement; anti-RNA polymerase III antibodies (ARAs) with scleroderma renal crisis and higher mRSS; anti-U3RNP antibodies with diffuse cutaneous disease and renal involvement; and anti-Ku antibodies with overlap syndromes. <b>Conclusions:</b> In this large real-world SSc cohort, autoantibody status was strongly associated with distinct clinical phenotypes, confirming its value for disease stratification. While most established immuno-clinical associations were reproduced, some differences from international cohorts were observed, supporting the need for population-specific validation of autoantibody associations in SSc.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Architecture and Clinical Landscape of Immune Checkpoint Receptors and Ligands.","authors":"Milena Czosnek, Agata Sowa, Łucja Rolek, Ewelina Grywalska, Sebastian Mertowski, Paulina Mertowska","doi":"10.3390/antib15050084","DOIUrl":"10.3390/antib15050084","url":null,"abstract":"<p><p>Immune checkpoints (ICPs) are essential regulators of immune homeostasis, maintaining the balance between effective immune responses and tolerance to self-antigens. Dysregulation of ICP signaling may contribute to impaired immune surveillance, immune evasion, chronic inflammation, autoimmunity, persistent infections, and tumor progression. Consequently, ICP molecules are increasingly recognized not only as therapeutic targets but also as potential diagnostic, prognostic, predictive, and treatment-monitoring biomarkers. This review provides a comprehensive overview of the biological functions, signaling mechanisms, and clinical significance of major co-inhibitory and co-stimulatory ICP pathways, including PD-1/PD-L1/PD-L2, CTLA-4/CD28/CD80/CD86, LAG-3, TIM-3, TIGIT, BTLA, VISTA, ICOS, OX40, 4-1BB, GITR, CD27, CD40, and CD2, together with their corresponding ligands. Particular emphasis is placed on their biomarker potential in cancer and immune-mediated diseases. In addition, the review presents a bioinformatic characterization of ICP receptors and ligands based primarily on data available in UniProtKB and complementary bioinformatic resources. The analysis includes protein sequence length, molecular weight, theoretical isoelectric point, amino acid composition, subcellular localization, conserved and functional domains, protein family classification, post-translational modifications, isoforms, and selected structural features. Collectively, the available evidence indicates that ICPs constitute a structurally and functionally diverse group of immunoregulatory molecules with substantial biomarker potential. Integrating their molecular, structural, functional, and bioinformatic characteristics may improve disease classification, prognosis, patient stratification, treatment selection, and therapeutic monitoring. Such an integrated approach may also support the identification of novel biomarkers and therapeutic targets and contribute to the further development of precision and personalized medicine.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ca₁₆Mab-56, a Novel Anti-Cadherin-16/Ksp-Cadherin Monoclonal Antibody for Multiple Applications.","authors":"Yukari Ogura, Hiroyuki Suzuki, Mika K Kaneko, Yukinari Kato","doi":"10.3390/antib15050083","DOIUrl":"10.3390/antib15050083","url":null,"abstract":"<p><strong>Background/objectives: </strong>Cadherin-16 (CDH16, Ksp-cadherin) possesses unique seven extracellular cadherin repeats, and its expression is restricted to normal kidney epithelium. CDH16 is downregulated in renal cell carcinoma (RCC) and is associated with poor prognosis. Therefore, developing mAbs that specifically recognize cell-surface CDH16 is essential for tumor diagnosis and for isolating CDH16-positive renal epithelial cells.</p><p><strong>Methods: </strong>Anti-human CDH16 mAbs (designated as Ca₁₆Mabs) were developed by immunizing mice with CDH16-overexpressed tumor cells, followed by a high-throughput flow cytometry-based screening.</p><p><strong>Results: </strong>Among the 58 established Ca₁₆Mabs, a clone, Ca₁₆Mab-56 (IgG₁, κ), specifically recognized CDH16-overexpressed Chinese hamster ovary-K1 (CHO/CDH16) cells with no detectable cross-reactivity to 21 other CDHs in flow cytometry. Ca₁₆Mab-56 also detected endogenous CDH16 in human RCC cell lines (OS-RC-2 and KMRC-20) and normal kidney epithelial cell lines. The dissociation constant (<i>K</i>_D) values of Ca₁₆Mab-56 for CHO/CDH16 and OS-RC-2 were determined as 6.5 × 10^-9 M and 1.2 × 10^-9 M, respectively. Furthermore, Ca₁₆Mab-56 detected endogenous CDH16 by Western blotting and showed potent staining in normal kidney tubular epithelium and clear membranous staining in renal cell carcinoma in immunohistochemistry.</p><p><strong>Conclusions: </strong>Ca₁₆Mab-56 is a versatile tool for detecting CDH16 and has potential for tumor diagnosis.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seroprevalence of IgG Antibodies to Measles, Mumps, Rubella and Varicella in Adolescents with Documented Two-Dose MMR Vaccination: Cross-Sectional Study.","authors":"Mikhail P Kostinov, Ivan S Samolygo, Aristitsa M Kostinova, Natalya L Starikova, Marina A Manina, Valentina B Polishchuk, Albina S Pestova, Pavel I Zhuravlev, Anton S Antishin, Svetlana I Erdes","doi":"10.3390/antib15050082","DOIUrl":"10.3390/antib15050082","url":null,"abstract":"<p><p><b>Background</b>: Measles, mumps, and rubella outbreaks continue to occur despite high vaccination coverage, raising concerns about long-term vaccine-induced immunity. This study assessed serological protection against measles, mumps, rubella, and varicella in fully vaccinated Russian adolescents to identify immunity gaps and inform revaccination strategies. <b>Methods</b>: Serum IgG was quantified by commercial ELISA. Analytical cut-offs were: measles ≥ 0.18 IU/mL, rubella ≥ 30 IU/mL, mumps index ≥ 1.0 (index = OD/0.467), and varicella ≥ 1.0 IU/mL; equivocal results were classified as negative in the primary analysis and as positive in a sensitivity analysis. Geometric mean concentrations (GMC) were computed on the natural-logarithm scale. <b>Results</b>: Seropositivity differed markedly between infections (χ² 55.1; <i>p</i> < 0.001): rubella 81.4% (95% CI 74.6-86.7), varicella 57.7% (95% CI 49.8-65.2), mumps 53.2% (95% CI 45.4-60.9) and measles 41.0% (95% CI 33.6-48.9). GMC was lowest for measles (0.132; 95% CI 0.111-0.158) and highest for rubella (61.9; 95% CI 55.3-69.2). The measles estimate was sensitive to the treatment of equivocal results, rising to 53.2% (95% CI 45.4-60.9) at the manufacturer's cut-off of ≥0.12 IU/mL; rubella rose to 94.9% at ≥16 IU/mL. <b>Conclusions</b>: Lower seropositivity rates for measles and mumps were identified among fully vaccinated adolescents, which fall below standard epidemiological benchmarks. In contrast, rubella seropositivity was robust at 81.4%. Because the measles estimate depended strongly on the assay cut-off applied, and because enzyme immunoassays are known to underestimate seroprevalence relative to neutralization testing, these findings describe the distribution of circulating antibody rather than the prevalence of susceptibility and warrant confirmation in larger representative samples with neutralization testing.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Evolution of Artificial Intelligence in Antibody Design: From Structure-Based Engineering to Generative Models.","authors":"Ida Szataniak, Kacper Packi","doi":"10.3390/antib15050081","DOIUrl":"10.3390/antib15050081","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Artificial intelligence (AI) has transformed computational antibody engineering by enabling accurate prediction of antibody structures, rational optimization of therapeutic properties, and de novo antibody design. Recent advances in deep learning, protein language models, and generative AI have fundamentally changed the way antibodies are discovered and engineered. This review aims to present the historical evolution of computational antibody engineering, from early structure-based design strategies to modern AI-driven approaches, while highlighting the major computational tools, publicly available databases, current limitations, and future directions of the field. <b>Methods</b>: A comprehensive narrative review of the literature was conducted using PubMed, Scopus, Web of Science, and Google Scholar. Original research articles, methodological studies, and review papers published between 1985 and 2026 were evaluated. Publications were selected according to their scientific relevance, methodological quality, and contribution to the historical development of computational antibody engineering. <b>Results</b>: The review describes the progression of antibody engineering from phage display and structure-based computational methods to machine learning, deep learning, protein language models, and generative artificial intelligence. It summarizes key public databases supporting antibody research, discusses advances in antibody structure prediction and developability assessment, and reviews recent generative models capable of designing antibody sequences and structures. Current challenges, including limited experimental validation, dataset bias, prediction of highly flexible regions, model interpretability, and clinical translation, are also discussed. <b>Conclusions</b>: Artificial intelligence has fundamentally reshaped computational antibody engineering by integrating sequence, structural, and functional information into increasingly accurate predictive and generative frameworks. Although important challenges remain, recent developments indicate that AI-driven approaches will play an increasingly central role in the discovery and optimization of next-generation therapeutic antibodies.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Bispecific Antibodies and Antibody-Drug Conjugates for Colorectal Cancer Treatment.","authors":"Maya G Cappellino, Sean P Sullivan, Peyton C High, Tiffani A Blackburn, Kendra S Carmon","doi":"10.3390/antib15050080","DOIUrl":"10.3390/antib15050080","url":null,"abstract":"<p><p>Bispecific antibodies (bsAbs) and bispecific antibody-drug conjugates (bsADCs) represent promising classes of emerging targeted therapeutics with the potential to overcome tumor heterogeneity and resistance in colorectal cancer (CRC). BsAbs can simultaneously engage multiple tumor antigens or immune cells or bind two distinct epitopes within a single target, enabling mechanisms of action beyond the capabilities of monoclonal antibodies. Bispecific T cell engagers facilitate targeted destruction of tumors through immune cell recruitment, while dual immune checkpoint inhibitors enhance immune activation by blocking T cell inhibitory signals. Furthermore, bsAbs can mediate dual signaling pathway inhibition through binding multiple receptor tyrosine kinase receptors or other tumor cell surface proteins. BsADCs integrate the dual-antigen recognition of bsAbs with targeted payload delivery, utilizing receptor-mediated endocytosis to deliver potent cytotoxic payloads selectively to CRC cells, while minimizing systemic toxicity. Recent advances in bsAb engineering, linker chemistry, site-specific conjugation, and payload design have accelerated the development of bsADCs for solid tumors, including CRC. BsAbs and bsADCs provide opportunities to improve tumor selectivity, enhance internalization, overcome antigen escape, and expand the population of CRC patients eligible for targeted therapy. Emerging preclinical studies demonstrate encouraging anti-tumor activity for bispecific modalities in CRC, while early clinical trials are beginning to establish their translational potential. This review summarizes the current landscape of bsAbs and bsADCs in therapeutic development for CRC, highlighting key biological targets, engineering strategies, mechanisms of action, and clinical status. We also discuss the major challenges facing clinical translation and provide perspectives on future directions for bispecific therapies in CRC.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Festschrift Celebrating Dr. Dimiter Stanchev Dimitrov: Antibodies, Innovation, and Impact on Infectious Disease and Cancer Research.","authors":"Ponraj Prabakaran, Tianlei Ying, Wei Li","doi":"10.3390/antib15050078","DOIUrl":"10.3390/antib15050078","url":null,"abstract":"<p><p>Antibody therapeutics now span across oncology, infectious disease, and autoimmunity, and the molecules entering development are increasingly being engineered rather than merely selected [...].</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}