Antibody Therapeutics最新文献

A novel bispecific antibody CVL006 superior to AK112 for dual targeting of PD-L1 and VEGF in cancer therapy. 一种新的双特异性抗体CVL006在癌症治疗中优于AK112的PD-L1和VEGF双重靶向。

Antibody Therapeutics Pub Date : 2025-05-22 eCollection Date: 2025-07-01 DOI: 10.1093/abt/tbaf012

Chunyan Wang, Hao Huang, Zeng Song, Zhongyuan Li, Jinwen Huang, Liang Cao, Ziai Wu, Junfang Pan, XiaoBing Chen, Xiaokun Shen

{"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":"Background: 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.Methods: 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 in vivo efficacy comparisons to atezolizumab and PD-1/VEGF bispecific antibody AK112 (ivonescimab).Results: 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. In vivo 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.Conclusions: 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.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 3","pages":"189-196"},"PeriodicalIF":0.0,"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}

引用次数: 0

Matching placebo development for injectable biologics-a practical tutorial. 与注射用生物制剂相匹配的安慰剂开发——实用教程。

Antibody Therapeutics Pub Date : 2025-05-08 eCollection Date: 2025-07-01 DOI: 10.1093/abt/tbaf009

Lun Xin, Zhe Zhang, Kushan Shah, Venus Hashemi, Xuanyue Li, Grace Qin, Steven Ren, Wei Chen, Yunsong Li

{"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":"Background: 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.Methods: 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.Results: 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.Conclusions: 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.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 3","pages":"177-188"},"PeriodicalIF":0.0,"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}

引用次数: 0

Bypassing the immunosuppressive effects of CA125/MUC16 via re-engineered rituximab (NAV-006) to improve its antitumor activity in vivo. 通过重组利妥昔单抗（NAV-006）绕过CA125/MUC16的免疫抑制作用，提高其体内抗肿瘤活性。

Antibody Therapeutics Pub Date : 2025-04-24 eCollection Date: 2025-07-01 DOI: 10.1093/abt/tbaf008

Luigi Grasso, Bradford J Kline, Nicholas C Nicolaides

{"title":"Bypassing the immunosuppressive effects of CA125/MUC16 via re-engineered rituximab (NAV-006) to improve its antitumor activity in vivo.","authors":"Luigi Grasso, Bradford J Kline, Nicholas C Nicolaides","doi":"10.1093/abt/tbaf008","DOIUrl":"10.1093/abt/tbaf008","url":null,"abstract":"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 in vivo 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.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 3","pages":"171-176"},"PeriodicalIF":0.0,"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}

引用次数: 0

A review of conjugation technologies for antibody drug conjugates. 抗体药物偶联物的偶联技术综述。

Antibody Therapeutics Pub Date : 2025-04-17 eCollection Date: 2025-04-01 DOI: 10.1093/abt/tbaf010

Qirui Fan, Hu Chen, Guoguang Wei, Ding Wei, Zekun Wang, Lin Zhang, Jun Wang, Marie Zhu

{"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":"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.","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}

引用次数: 0

Preclinical development of mecbotamab vedotin (BA3011), a novel, AXL-specific conditional active biologic antibody-drug conjugate. mecbotamab vedotin （BA3011）的临床前开发，一种新型的axl特异性条件活性生物抗体-药物偶联物。

Antibody Therapeutics Pub Date : 2025-04-10 eCollection Date: 2025-04-01 DOI: 10.1093/abt/tbaf006

Hwai Wen Chang, Jing Wang, Haizhen Liu, Charles Xing, Jian Chen, Gerhard Frey, William J Boyle, Jay M Short

{"title":"Preclinical development of mecbotamab vedotin (BA3011), a novel, AXL-specific conditional active biologic antibody-drug conjugate.","authors":"Hwai Wen Chang, Jing Wang, Haizhen Liu, Charles Xing, Jian Chen, Gerhard Frey, William J Boyle, Jay M Short","doi":"10.1093/abt/tbaf006","DOIUrl":"10.1093/abt/tbaf006","url":null,"abstract":"Background: AXL, a tyrosine kinase receptor, is over-expressed in many solid and hematologic cancers, promoting progression and poor clinical outcomes. It also contributes to resistance against chemotherapeutic agents, especially tyrosine kinase inhibitors, by upregulating AXL signaling or switching oncogenic pathways. These factors make AXL an attractive therapeutic target. However, early attempts with naked antibody therapies failed due to the high doses need for efficacy, and antibody-drug conjugates (ADCs) targeting AXL were hindered by off-tumor toxicities due to its expression on normal tissues.Methods: To address these issues, we developed a novel, conditionally active biologic ADC, mecbotamab vedotin (BA3011), which selectively binds to AXL in the acidic tumor microenvironment. In healthy tissue, binding to AXL is substantially diminished due to a powerful selection mechanism utilizing naturally occurring, physiological chemicals referred to as Protein-associated Chemical Switches. BA3011 was tested in vitro and in vivo against AXL expressing cancer cells.Results: Mecbotamab vedotin demonstrates the expected AXL, tumor-specific binding properties and effectively induced lysis of AXL-positive cancer cell lines in vitro. In vivo, mecbotamab vedotin exhibited potent and lasting antitumor effects in human cancer xenograft mouse models. Furthermore, in nonhuman primates, mecbotamab vedotin demonstrated excellent tolerability at doses of up to 5 mg/kg and maintained linker-payload stability in vivo.Conclusions: These findings indicate that mecbotamab vedotin has the potential to be a robust and less toxic therapeutic agent, offering promise as a treatment for patients with AXL-positive cancers.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 2","pages":"145-156"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259076","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}

引用次数: 0

Overview of antibody-drug conjugates nonclinical and clinical toxicities and related contributing factors. 抗体-药物偶联物的非临床和临床毒性及其相关影响因素综述。

Antibody Therapeutics Pub Date : 2025-03-18 eCollection Date: 2025-04-01 DOI: 10.1093/abt/tbaf004

Yumei Cheng, Jing Lu, Chonghao Zhang, Weiyuan Yan, Panpan Zhu, Qiuping Qin, Likun Gong

引用次数: 0

Fundamental properties and principal areas of focus in antibody-drug conjugates formulation development. 抗体-药物偶联物配方开发的基本特性和主要关注领域。

Antibody Therapeutics Pub Date : 2025-03-09 eCollection Date: 2025-04-01 DOI: 10.1093/abt/tbaf005

Lili Wen, Yuanyuan Zhang, Chenxi Sun, Shawn Shouye Wang, Yuhui Gong, Chunyuan Jia, Jianjun Luo

{"title":"Fundamental properties and principal areas of focus in antibody-drug conjugates formulation development.","authors":"Lili Wen, Yuanyuan Zhang, Chenxi Sun, Shawn Shouye Wang, Yuhui Gong, Chunyuan Jia, Jianjun Luo","doi":"10.1093/abt/tbaf005","DOIUrl":"10.1093/abt/tbaf005","url":null,"abstract":"Antibody-drug conjugates (ADCs) have emerged as a rapidly expanding class of therapeutics driven by their superior specificity and clinical efficacy. 14 out of 16 commercially approved ADCs are formulated as lyophilized forms because ADC is generally considered to be less stable than unmodified antibody. The formulation development for ADCs, particularly liquid formulation, presents unique challenges due to their intricate structural complexity, physicochemical properties, and degradation pathways. This review provides the first comprehensive analysis of formulation strategies employed in commercial ADCs. Furthermore, this review discusses the key areas of focus for ADCs throughout the formulation development workflow, spanning from the initial formulation development to the final stage of drug product manufacturing. In addition, we identify and analyze the distinctive technical challenges in ADC formulation development compared to unconjugated antibody, while proposing potential solutions to these challenges. Finally, we offer strategic perspectives on future directions in ADC formulation development to advance this promising therapeutic modality.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 2","pages":"99-110"},"PeriodicalIF":0.0,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774573","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}

引用次数: 0

A systematic review of the avian antibody (IgY) therapeutic effects on human bacterial infections over the decade. 近十年来禽抗体（IgY）治疗人细菌感染效果的系统综述。

Antibody Therapeutics Pub Date : 2025-03-09 eCollection Date: 2025-04-01 DOI: 10.1093/abt/tbaf007

Zahra Esmaeili, Sara Kamal Shahsavar, Kiarash Ghazvini

{"title":"A systematic review of the avian antibody (IgY) therapeutic effects on human bacterial infections over the decade.","authors":"Zahra Esmaeili, Sara Kamal Shahsavar, Kiarash Ghazvini","doi":"10.1093/abt/tbaf007","DOIUrl":"10.1093/abt/tbaf007","url":null,"abstract":"The overuse of antibiotics worldwide, especially during the Coronavirus pandemic, has raised concerns about the rise of antibiotic resistance and its side effects. Immunoglobulin Y, a natural protein that specifically targets foreign antigens, holds promise as a potential therapeutic option, particularly for individuals with sensitive immune systems. Despite numerous studies on IgY, the optimal administration method, effective dose, target antigen, and potential side effects of this antibody remain areas of active research and challenge. This review selected and evaluated articles published in the last ten years from databases such as PubMed and Science Direct with appropriate keywords discussing the therapeutic effects of immunoglobulin Y in human infections in vivo. Out of all the reviewed articles, 35 articles met the inclusion criteria. The results showed that the specific antibody against dental, respiratory, and skin infections has an acceptable effectiveness. In contrast, some infections, such as neurological infections, including tetanus and botulism, still need further investigation due to the short survival time of mice. On the other hand, reporting side effects such as antibody-dependent enhancement in some infections limits its use.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 2","pages":"111-123"},"PeriodicalIF":0.0,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774483","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}

引用次数: 0

Fc gamma receptor polymorphisms in antibody therapy: implications for bioassay development to enhance product quality. 抗体治疗中的Fc γ受体多态性：对提高产品质量的生物测定发展的影响。

Antibody Therapeutics Pub Date : 2025-01-21 eCollection Date: 2025-04-01 DOI: 10.1093/abt/tbaf003

Julianne D Twomey, Sasha George, Baolin Zhang

引用次数: 0

Near-infrared photoimmunotherapy: mechanisms, applications, and future perspectives in cancer research. 近红外光免疫疗法：在癌症研究中的机制、应用和未来展望。

Antibody Therapeutics Pub Date : 2025-01-20 eCollection Date: 2025-01-01 DOI: 10.1093/abt/tbaf001

Derek Allen, Madeline JoAnna Szoo, Tessa D van Bergen, Ani Seppelin, Jeonghyun Oh, Mohammad A Saad

{"title":"Near-infrared photoimmunotherapy: mechanisms, applications, and future perspectives in cancer research.","authors":"Derek Allen, Madeline JoAnna Szoo, Tessa D van Bergen, Ani Seppelin, Jeonghyun Oh, Mohammad A Saad","doi":"10.1093/abt/tbaf001","DOIUrl":"10.1093/abt/tbaf001","url":null,"abstract":"Photoimmunotherapy (PIT) involves the targeted delivery of a photosensitizer through antibody conjugation, which, upon binding to its cellular target and activation by external irradiation, induces localized toxicity. This approach addresses several limitations of conventional cancer therapies, such as chemo- and radiotherapies, which result in off-target effects that significantly reduce patient quality of life. Furthermore, PIT improves on the challenges encountered with photodynamic therapy (PDT), such as nonspecific localization of the photosensitizer, which often results in unintended toxicities. Although PIT was first proposed in the early 1980s, its clinical applications have been constrained by limitations in antibody engineering, conjugation chemistries, and optical technologies. However, recent advances in antibody-drug conjugate (ADC) research and the emergence of sophisticated laser technologies have greatly benefited the broader applicability of PIT. Notably, the first near-infrared photoimmunotherapy (NIR-PIT) treatment for head and neck cancer has been approved in Japan and is currently in phase III clinical trials in the USA. A significant advantage of PIT over traditional ADCs in cancer management is the agnostic nature of PDT, making it more adaptable to different tumor types. Specifically, PIT can act on cancer stem cells and cancer cells displaying treatment resistance and aggressive phenotypes-a capability beyond the scope of ADCs alone. This review provides an overview of the mechanism of action of NIR-PIT, highlighting its adaptability and application in cancer therapeutics, and concludes by exploring the potential of PIT in advancing cancer treatments.","PeriodicalId":36655,"journal":{"name":"Antibody Therapeutics","volume":"8 1","pages":"68-85"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433820","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}

引用次数: 0