Antibody Therapeutics最新文献

{"title":"Reprogramming the tumor microenvironment: synergistic mechanisms of antibody-drug conjugates and immune checkpoint inhibitors.","authors":"Ling Yin, Shoubing Zhou, Hongliang Zhang, Chengbing Yao, Zaid Talal Abdulqader Al-Qadhi, Yuhua Shang, Songquan Wu, Tengchuan Jin","doi":"10.1093/abt/tbaf017","DOIUrl":"10.1093/abt/tbaf017","url":null,"abstract":"<p><p>The integration of antibody-drug conjugates (ADCs) with immune checkpoint inhibitors (ICIs) represents a paradigm shift in oncology, combining targeted cytotoxicity and adaptive immune activation to overcome resistance in refractory tumors. This review explores their mechanistic synergy, focusing on dual functions in reprogramming the tumor immune microenvironment. ADCs mediate antibody-dependent cellular cytotoxicity (ADCC), engaging NK cells and macrophages to release tumor-associated antigens (TAAs) and damage-associated molecular patterns. Immunogenic cell death (ICD) amplifies adaptive immunity by releasing TAAs for T-cell priming, while PD-L1 upregulation creates a targetable niche for PD-1/PD-L1 inhibitors. This strategy sustains interferon-γ signaling and drives effector T-cell differentiation, but overlapping immunostimulatory signals raise risks of cytokine release syndrome and immune-related adverse events, requiring biomarker-guided risk stratification. We propose a multidimensional immune microenvironment reprogramming framework, integrating tumor-infiltrating lymphocyte phenotyping, serum biomarkers, and spatial transcriptomic mapping, to optimize ADC-ICI therapy and balance efficacy with immunopathology.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 3","pages":"262-274"},"PeriodicalIF":4.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12451267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132100","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":"Opportunities in formulation development of antibody-based therapeutics.","authors":"Qingyan Hu, Yunsong Frank Li","doi":"10.1093/abt/tbaf016","DOIUrl":"10.1093/abt/tbaf016","url":null,"abstract":"<p><p>Drug product formulation transforms active pharmaceutical ingredients into drug products, ensuring stability, manufacturability, efficacy, and patient safety. Driven by biotech advancements and patient needs, new antibody-based therapies and combinations are expanding, significantly evolving the formulation landscape. This editorial provides an overview of formulations for antibody-based therapeutics and highlights a few hot topics and emerging trends, including high concentration formulations, fixed-dose combinations, novel excipients and delivery technologies, and AI integration. As the field progresses, innovative technologies and sustainable practices will be important in addressing the increasing demand for antibody-based therapies.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 3","pages":"259-261"},"PeriodicalIF":4.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12451266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132156","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":"Correction to: Structure and function of therapeutic antibodies approved by the US FDA in 2024.","authors":"","doi":"10.1093/abt/tbaf015","DOIUrl":"10.1093/abt/tbaf015","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/abt/tbaf014.].</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 3","pages":"238"},"PeriodicalIF":4.5,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144972449","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":"Broadly reactive anti-VHH antibodies for characterizing, blocking, or activating nanobody-based CAR-T cells.","authors":"Scott McComb, Bianca Dupont, Alex Shepherd, Bigitha Bennychen, Anne Marcil, Laura Tamblyn, Shalini Raphael, Joey Sheff, Greg Hussack, Anna N Moraitis, Cunle Wu, Annie Aubry, Christine Gadoury, Julie Lippens, Martine Pagé, Annie Fortin, Simon Joubert, Linda Lamoureux, Marie Parat, Pierre Plante, Félix Malenfant, Mauro Acchione, Petra Pohankova, Joe Schrag, Andrea Acel, Mathieu Coutu, Emma Smith, Majida El Bakkouri, Jennifer J Hill, Tammy-Lynn Tremblay, Aziza P Manceur, Sharlene Faulkes, John Webb, Ahmed Zafer, Qin Zhu, Tina Nguyen, Robert A Pon, Risini D Weeratna, Mehdi Arbabi-Ghahroudi","doi":"10.1093/abt/tbaf011","DOIUrl":"10.1093/abt/tbaf011","url":null,"abstract":"<p><strong>Background: </strong>Production of chimeric antigen receptor T cell (CAR-T) therapies depends on antibody reagents to label, isolate, and expand T cell products. We sought to create antibody tools specific for the variable domain of heavy-chain only antibodies (VHHs), also known as nanobodies, used in some CARs.</p><p><strong>Methods: </strong>We immunized a mouse with VHH and selected two murine monoclonal antibodies (mAbs) that bind to distinct epitopes in conserved framework regions of llama-derived VHHs, and not to human VH domains. Anti-VHH mAbs were characterized by enzyme-linked immunosorbent assay, surface plasmon resonance, and hydrogen-deuterium exchange mass spectrometry; were then tested for cell/tissue labeling and for modulating cellular activity in VHH-CAR-T cells.</p><p><strong>Results: </strong>We produced a high-quality dual-clonal anti-VHH antibody product and confirmed reactivity to over 98% of VHH proteins regardless of their antigenic specificity, with no reactivity to human or mouse IgG and reduced reactivity to conventional llama or alpaca IgG. Anti-VHH binding did not disrupt VHH/antigen interaction, and thus was appropriate for secondary labeling to assess cellular or tissue reactivity of VHH molecules. Despite not interfering with antigen binding, anti-VHH antibodies (Abs) potently blocked VHH-CAR-T activation and cytolytic killing of target cells. When immobilized, anti-VHH Abs induced strong activation and expansion of VHH CAR-T cells; with 730-fold mean expansion, >94% CAR purity, and retained CD8/CD4 heterogeneity. Functionally, anti-VHH antibody-expanded CAR-T cells maintained strong antigen-specific activity without functional exhaustion.</p><p><strong>Conclusions: </strong>Overall, these data identify useful anti-VHH mAbs that can be applied to better understand and manipulate VHH-based CAR-T cells or other VHH-based immunotherapies.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 3","pages":"242-258"},"PeriodicalIF":4.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12451263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132113","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":"Structure and function of therapeutic antibodies approved by the US FDA in 2024.","authors":"William R Strohl","doi":"10.1093/abt/tbaf014","DOIUrl":"10.1093/abt/tbaf014","url":null,"abstract":"<p><p>In 2024, the Food and Drug Administration approved 47 new molecular entities (NMEs), including 15 therapeutic antibody-based molecules, marking the 30th anniversary of the first approved recombinant antibody. Ten of these were recombinant immunoglobulin G antibodies, while the rest comprised three bispecific antibodies, one immunocytokine, and one Fc-fusion protein. Seven antibodies targeted previously approved targets like programmed cell death receptor-1, programmed cell death receptor ligand-1, complement factor C5, interleukin (IL)-13, human epidermal growth factor receptor 2 (HER2) (biparatopic), and a novel form of amyloid-beta for conditions like esophageal squamous cell carcinoma, cutaneous squamous cell carcinoma, paroxysmal nocturnal hemoglobinuria, atopic dermatitis, biliary tract cancer, and Alzheimer's disease, respectively. The other seven recognized novel targets such as activin for pulmonary arterial hypertension, IL-15Rβγ agonist for bladder cancer, delta-like ligand-3 × cluster of differentiation-3 for small cell lung cancer (SCLC), IL-31 receptor for prurigo nodularis, colony stimulating factor-1 receptor for graft-versus-host disease, tissue factor pathway inhibitor for Hemophilia A and B, and claudin 18.2 for gastric or gastroesophageal junction cancers. Additionally, a HER2-HER3 bispecific antibody was approved for non-SCLC and pancreatic adenocarcinoma. Three reformulated antibodies with hyaluronidase HP20 for subcutaneous administration were also approved, although not as New Molecular Entities (NME)s.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 3","pages":"197-237"},"PeriodicalIF":4.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139056","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-drug conjugates in cancer and beyond: progress, promise, and perspectives.","authors":"Victor S Goldmacher","doi":"10.1093/abt/tbaf013","DOIUrl":"10.1093/abt/tbaf013","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) are transforming cancer therapy by combining antibody specificity with potent cytotoxic agents, enabling targeted tumor cell killing while minimizing systemic toxicity. This special collection of Antibody Therapeutics presents a wide overview of recent advances in ADC research and development. Topics include targeting strategies, antibody formats, innovative payloads and bispecific apoptosis triggers, formulation strategies, toxicity profiling, and conjugation technologies. Together, these contributions reflect the rapid evolution of the ADC field and point toward safer, more effective therapies for cancer and beyond.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 3","pages":"239-241"},"PeriodicalIF":4.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144972492","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 novel bispecific antibody CVL006 superior to AK112 for dual targeting of PD-L1 and VEGF in cancer therapy.","authors":"Chunyan Wang, Hao Huang, Zeng Song, Zhongyuan Li, Jinwen Huang, Liang Cao, Ziai Wu, Junfang Pan, XiaoBing Chen, Xiaokun Shen","doi":"10.1093/abt/tbaf012","DOIUrl":"10.1093/abt/tbaf012","url":null,"abstract":"<p><strong>Background: </strong>Preclinical and clinical studies highlight the enhanced anticancer efficacy of combining anti-VEGF/VEGFR drugs with immune checkpoint inhibitors (ICIs). PD-L1/VEGF bispecific antibodies outperform monotherapy or combined PD-L1 inhibitors and anti-VEGF antibodies by simultaneously blocking the PD-1/PD-L1 immune pathway and VEGF-driven angiogenesis, providing a dual mechanism for superior antitumor activity.</p><p><strong>Methods: </strong>We developed CVL006, a novel bispecific antibody, by fusing an anti-PD-L1 VHH domain with a humanized IgG1 anti-VEGF monoclonal antibody. CVL006 retains antibody-dependent cellular cytotoxicity (ADCC) functionality. Preclinical evaluations included binding affinity and specificity assessments, dual-pathway blockade testing, and <i>in vivo</i> efficacy comparisons to atezolizumab and PD-1/VEGF bispecific antibody AK112 (ivonescimab).</p><p><strong>Results: </strong>CVL006 demonstrated high affinity and specificity for human PD-L1 and VEGF. It effectively inhibited VEGF/VEGFR signaling and the PD-L1/PD-1 axis, suppressing VEGF-induced angiogenesis and reactivating T cells. This reactivation led to increased cytokine secretion critical for immune response. <i>In vivo</i> studies revealed CVL006's superior antitumor efficacy, achieving greater tumor growth inhibition and angiogenesis suppression than atezolizumab. CVL006 also outperformed AK112 in preclinical models, showcasing robust antitumor activity.</p><p><strong>Conclusions: </strong>CVL006 integrates immune checkpoint inhibition and tumor vascularization disruption, offering a comprehensive anticancer strategy. Its superior preclinical performance compared to atezolizumab and AK112 underscores its therapeutic potential, paving the way for further development and clinical translation.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 3","pages":"189-196"},"PeriodicalIF":4.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530124","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":"Matching placebo development for injectable biologics-a practical tutorial.","authors":"Lun Xin, Zhe Zhang, Kushan Shah, Venus Hashemi, Xuanyue Li, Grace Qin, Steven Ren, Wei Chen, Yunsong Li","doi":"10.1093/abt/tbaf009","DOIUrl":"10.1093/abt/tbaf009","url":null,"abstract":"<p><strong>Background: </strong>In drug development, placebo-controlled trials are vital for assessing treatment efficacy. Developing a suitable placebo for injectable biologics presents unique challenges, particularly in matching the physical characteristics of the active drug without containing its active pharmaceutical ingredient.</p><p><strong>Methods: </strong>Our study developed a methodology for biologic placebo formulations, focusing on color and viscosity matching, in relevant chemical matrixes. A custom color deconvolution algorithm was used for precise color-matching, and sodium carboxymethyl cellulose (Na-CMC) was employed to adjust viscosity in different buffer systems. The interactions between buffers, color agents, and excipients were investigated to ensure consistency in physical properties. Stability testing was conducted under freeze/thaw and thermal stress conditions.</p><p><strong>Results: </strong>The color-matching algorithm successfully achieved visually indistinguishable results from the active drug, measured by an empirical parameter for color differences (ΔE values). Na-CMC was effective in matching the viscosity of biologic formulations, maintaining the desired physical appearance. Significant interactions between color agents and buffer systems influenced viscosity and osmolality. Stability tests confirmed that the placebo formulations retained their color, pH, and osmolality, with only minor viscosity changes after stress testing.</p><p><strong>Conclusions: </strong>Our study presents a systematic approach to biologic placebo development, providing a reliable framework for matching the color and viscosity of biologics. The methods and findings support the use of tailored excipients and color-matching algorithms to ensure clinical blinding in trials, enhancing the rigor of drug efficacy assessments and contributing to future placebo design in biologic drug development.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 3","pages":"177-188"},"PeriodicalIF":4.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530126","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":"Bypassing the immunosuppressive effects of CA125/MUC16 via re-engineered rituximab (NAV-006) to improve its antitumor activity <i>in vivo</i>.","authors":"Luigi Grasso, Bradford J Kline, Nicholas C Nicolaides","doi":"10.1093/abt/tbaf008","DOIUrl":"10.1093/abt/tbaf008","url":null,"abstract":"<p><p>The monoclonal antibody rituximab functions through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) and is used to treat non-Hodgkin's lymphoma. Elevated serum CA125/MUC16 levels, present in some follicular lymphoma patients, have been shown to correlate with reduced efficacy of rituximab. Previous studies revealed that CA125/MUC16 binds to rituximab, diminishing its CDC and ADCC. A rituximab variant, NAV-006, was engineered to counteract CA125/MUC16's immunosuppressive effects. NAV-006 demonstrated enhanced CDC and ADCC activities and was unaffected by CA125/MUC16. In the present study, NAV-006 showed improved <i>in vivo</i> antitumor activity compared to rituximab in a human lymphoma model with reconstituted CA125/MUC16. Additionally, CA125/MUC16 bound to newer antibody-based lymphoma treatment agents, including obinutuzumab and tafasitamab, suppressing their immune effector functions. Bispecific antibodies mosunetuzumab and glofitamab also exhibited reduced cytotoxicity in the presence of CA125/MUC16. These findings suggest that NAV-006 could improve therapeutic efficacy in B-cell lymphomas, particularly in patients with elevated CA125/MUC16 levels.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 3","pages":"171-176"},"PeriodicalIF":4.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530125","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 review of conjugation technologies for antibody drug conjugates.","authors":"Qirui Fan, Hu Chen, Guoguang Wei, Ding Wei, Zekun Wang, Lin Zhang, Jun Wang, Marie Zhu","doi":"10.1093/abt/tbaf010","DOIUrl":"10.1093/abt/tbaf010","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) have gained significant attention in biotherapeutics after several years of steady development. Among the multiple factors influencing ADC design, the conjugation method is one of the most critical parameters. This review classifies conjugation strategies into three categories: non-specific, site-specific but non-selective, and fully site-specific and selective methods. The characteristics; advantages and disadvantages; chemistry, manufacturing, and controls (CMC) potential; and clinical status of each conjugation strategy are discussed in detail. The site-specific and selective methods will yield more homogeneous ADC, which may influence the stability and pharmacokinetics (PK) profile of the ADC and then influence the final therapeutic outcome. Additionally, the review also explores challenges and future directions for developing novel conjugation strategies. This review presents the most prevalent conjugation techniques, providing a valuable resource for researchers in selecting conjugation technologies and advancing ADC development.</p>","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 2","pages":"157-170"},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259074","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}