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.

Oncology letters4区 · 医学

Block‑Removed Immunoglobulin Technology to enhance rituximab effector function by counteracting CA125‑mediated immunosuppression

4区 · 医学

Article

作者: Grasso, Luigi ; Nicolaides, Nicholas ; Kline, James

Rituximab (RTX) is a CD20-targeting antibody that is the standard-of-care for patients with non-Hodgkin Lymphoma (NHL) cases. RTX's mechanism of action includes complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Recent clinical evidence suggests that high serum levels of the tumor-produced mucin 16 (MUC16) and cancer antigen 125 (CA125) have a negative impact on the effectiveness of RTX clinical activity in up to 40% of patients with follicular lymphoma. The present study sought to understand the possible mechanism underlying these results; therefore, cellular and molecular analyses of RTX and CA125 interaction were peformed, and a library of RTX variants was generated using a proprietary technology called Block-Removed Immunoglobulin Technology that combines randomized amino acid substitutions and high-throughput functional screenings to identify CA125-refractory RTX variants. The present study demonstrated that CA125 could bind to RTX and reduce its tumor cell killing activity. Furthermore, the study characterized an RTX variant, named NAV-006 (RTX-N109D), which was more refractory to the immunosuppressive effects mediated by CA125 as evidenced by its reduced CA125 interaction and increased activity of ADCC and CDC when compared with parent RTX. Taken together, these findings warranted further investigation on NAV-006 as a next generation anti-CD20 antibody that could improve the efficacy of parent RTX in NHL patients with high levels of CA125.

项与 Rituximab biobetter (Navrogen) 相关的新闻（医药）

2025-12-09

·今日头条

《Antibody Therapeutics》2025年第3期精选研究进展

Antibody Therapeutics 2025年第三期聚焦于多项抗体工程进展，包括能够绕过 MUC16/CA125 介导免疫抑制的改良型利妥昔单抗 NAV-006。该期还介绍了注射型生物制剂匹配安慰剂的开发方法、双特异性 PD-L1/VEGF 抗体 CVL006 的研发进展，以及用于支持纳米抗体（VHH）CAR-T 技术的广谱抗-VHH 抗体。综述部分总结了 2024 年 FDA 批准的所有治疗性抗体，并探讨了 ADC 与免疫检查点抑制剂联合使用以重塑肿瘤微环境的策略。社论则强调 ADC 平台的快速演进，关注更创新的靶向策略、载荷以及安全性优化。本期网址： https://academic.oup.com/abt/issue/8/3 本期亮点速览 1. 通过重构利妥昔单抗 NAV‑006 绕过 CA125/MUC16 介导的免疫抑制并提高体内抗肿瘤活性：工程化改造利妥昔单抗以减弱与 CA125/MUC16 的相互作用；在临床前模型中显示 NAV‑006 可部分恢复效应功能并增强抗肿瘤活性。 https://doi.org/10.1093/abt/tbaf008 2. 注射用生物药匹配安慰剂开发的实践教程：提出一套面向注射用生物药的匹配安慰剂开发流程；通过颜色解卷积算法和 Na‑CMC 等辅料匹配颜色、黏度、pH 与渗透压，以更好保障高浓度制剂临床试验的盲法和用药体验一致性。 https://doi.org/10.1093/abt/tbaf009 3. 新型 PD‑L1/VEGF双特异性抗体 CVL006 在肿瘤治疗中的开发：构建将抗 PD‑L1 VHH 与抗 VEGF IgG1 融合的双特异性抗体 CVL006；临床前数据显示其在双重阻断和抗肿瘤活性方面优于阿替利珠单抗和AK112。 https://doi.org/10.1093/abt/tbaf012 4. 广谱抗 VHH 抗体用于纳米抗体 CAR‑T 细胞的表征与调控：开发一组能广泛识别重链单域抗体 (VHH) 的抗体工具；可用于定量、分选、抑制或激活纳米抗体 CAR‑T 细胞，为工程化细胞治疗开发提供通用试剂。 https://doi.org/10.1093/abt/tbaf011 5. 2024 年美国 FDA 批准治疗性抗体的结构与功能综述：总结 2024 年美国 FDA 批准的 15 个治疗性抗体；系统梳理其结构类型、作用机制和临床适应症，反映当年抗体药物开发趋势。 https://doi.org/10.1093/abt/tbaf014 6. 肿瘤微环境重编程：抗体药物偶联物 (ADC) 与免疫检查点抑制剂的协同机制：系统阐明 ADC 与免疫检查点抑制剂在肿瘤微环境重编程中的互补作用；提出多维度免疫微环境重塑框架，为优化联合方案和拓展难治性肿瘤治疗指数提供思路。 https://doi.org/10.1093/abt/tbaf017 7. 抗体药物偶联物(ADC) 在癌症及更广领域中的应用：进展、前景与展望：综述 ADC 在靶向策略、分子格式、载荷、制剂、毒性与偶联技术等方面的最新进展；探讨其在癌症及非肿瘤疾病中的未来应用前景。 https://doi.org/10.1093/abt/tbaf013 8. 抗体药物制剂开发的新机遇：梳理抗体类药物制剂开发的关键方向，包括高浓度制剂、固定剂量联合、创新赋形剂与递送技术及 AI 赋能等；旨在促进更安全、稳健且以患者为中心的制剂设计。 https://doi.org/10.1093/abt/tbaf016 阅读本期内容 Volume 8, Issue 3 (2025) 1. Bypassing the immunosuppressive effects of CA125/MUC16 via re-engineered rituximab (NAV-006) to improve its antitumor activity in vivo . Corresponding author: Luigi Grasso, R&D Department, Navrogen Inc., 1837 University Circle, Cheyney, PA 19319, United States; E-mail: luigi@navrogen.com Antibody Therapeutics, 2025, 8(3): 171-176. https://doi.org/10.1093/abt/tbaf017 2. Matching placebo development for injectable biologics—a practical tutorial. Corresponding author: Yunsong Li, BioDev Department, WuXi Biologics, 1 Cedarbrook Dr, Cranbury, NJ 08512, United States; E-mail: Yunsong.li@WuXibiologics.com Antibody Therapeutics, 2025, 8(3): 177-188. https://doi.org/10.1093/abt/tbaf009 3. A novel bispecific antibody CVL006 superior to AK112 for dual targeting of PD-L1 and VEGF in cancer therapy. Corresponding author(s): Xiaokun Shen, Convalife Pharmaceuticals, Shanghai, China; E-mail: steve.shen@convalife.com; XiaoBing Chen, Department of Oncology, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China; E-mail: zlyychenxb0807@zzu.edu.cn Antibody Therapeutics, 2025, 8(3): 189-196. https://doi.org/10.1093/abt/tbaf012 4. Broadly reactive anti-VHH antibodies for characterizing, blocking, or activating nanobody-based CAR-T cells. Corresponding author: Scott McComb, Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON K1A 0R6, Canada; E-mail: scott.mccomb@nrc-cnrc.gc.ca Antibody Therapeutics, 2025, 8(3): 242-258. https://doi.org/10.1093/abt/tbaf011 5. Structure and function of therapeutic antibodies approved by the US FDA in 2024. Corresponding author: William R Strohl, BiStro Biotechnology Consulting, 1086 Tullo Farm Rd, Bridgewater, NJ 08807, United States; E-mail: wrstrohl@gmail.com Antibody Therapeutics, 2025, 8(3): 197–237. https://doi.org/10.1093/abt/tbaf014 6. Reprogramming the tumor microenvironment: synergistic mechanisms of antibody–drug conjugates and immune checkpoint inhibitors. Corresponding author(s): Tengchuan Jin and Songquan Wu, Center of Disease Immunity and Intervention, College of Medicine, Lishui University, Lishui 323000, China; E-mail: jint@ustc.edu.cn; lswsq163@163.com Antibody Therapeutics, 2025, 8(3): 262–274. https://doi.org/10.1093/abt/tbaf017 7. Antibody–drug conjugates in cancer and beyond: progress, promise, and perspectives. Corresponding author: Victor S Goldmacher, Research and Development Department, ImmuVia, Inc., 245 First Street, Cambridge, MA 02142, United States; E-mail: cso@immuvia.com Antibody Therapeutics, 2025, 8(3): 239–241. https://doi.org/10.1093/abt/tbaf013 8. Opportunities in formulation development of antibody-based therapeutics. Corresponding author: Yunsong (Frank) Li, Drug Product Development, Biopharmaceuticals, Eli Lilly and Company, Indianapolis, IN 46221, United States; E-mail: frank.li@lilly.com Antibody Therapeutics, 2025, 8(3): 259–261. https://doi.org/10.1093/abt/tbaf016 期刊简介《Antibody Therapeutics》是华人抗体协会（ChAbS）的旗下期刊，由牛津大学出版社（Oxford University Press）出版。作为一本同行评审的开放获取期刊，Antibody Therapeutics 为全球科学界提供了一个平台，用于发表治疗性抗体在发现、研究、开发及相关方法学方面的最新进展与挑战。该期刊已被ESCI（影响因子=4.5）、Scopus（CiteScore=8.4）及PubMed Central等主要文献数据库收录。期刊官网： https://academic.oup.com/abt

2025-09-29

·EINPresswire

Navrogen Granted Patent to Develop Antibodies That Are Refractory to Immunosuppressive Humoral Immuno-Oncology Factors

Navrogen Granted Patent to Develop Antibodies and Next Gen Antibody Formats That Are Refractory to Immunosuppressive Humoral Immuno-Oncology (HIO) Factors CHEYNEY, PA, UNITED STATES, September 29, 2025 / EINPresswire.com / -- Navrogen, Inc ., a biopharmaceutical company specialized in developing antibody-based therapies for cancer, announced today that the United States Patent and Trademark Office has granted the company Patent No. 12,416,642. The patent covers Navrogen’s platform technology that detects native antibodies (mAbs) and next gen antibody formats susceptible to humoral immuno-oncology (HIO) factor immunosuppression. The patent also covers the application of the technology to direct the engineering of HIO-refractory mAbs, T-cell engager antibodies (TCEs) and antibody-drug conjugates (ADCs) as well as for screening small chemical libraries to identify HIO factor antagonists. HIO factors are tumor-derived proteins that bind to mAbs, TCEs and ADCs, which then change their dynamic structure leading to suppressed antibody-mediated cytotoxicity against target cells. HIO-factor immunosuppression of mAbs results from allosteric changes that perturb their ability to engage with natural killer cells through the CD16a Fc-receptor, thereby impairing humoral immune-mediated tumor cytotoxicity. HIO factor binding to TCEs alters the spatial distancing of the tumor antigen and T-cell CD3 binding domains thereby reducing optimal tumor/T-cell synapse, while HIO factor binding to ADCs results in reduced ADC tumor cell internalization, a requirement for maximal ADC target cell killing. “We have applied our proprietary platform technology to develop several HIO-refractory mAb, TCE and ADC therapeutic agents as well as discover small molecule HIO factor antagonists in our pipeline,” stated Dr. Nicholas Nicolaides, Chief Executive Officer of Navrogen. “These unique HIO-refractory agents, such as NAV-001 anti-mesothelin ADC, NAV-310 anti-HER2 ADC, NAV-106 anti-CD20:CD3 TCE and NAV-006 anti-CD20 mAb offer the medical community alternative therapies to address cancer patients with HIO-positive cancers for which current therapies are inadequate. ” The company is currently advancing several of these agents towards proof-of-concept clinical trials. About Navrogen Navrogen is a biotechnology company focused on the discovery of tumor-produced Humoral Immuno-Oncology (HIO) factors that are associated with suppressed humoral immunity, poor prognosis and limited therapeutic response of immune-mediated anti-cancer therapies. The company’s mission is to develop best and first-in-class agents that can overcome the immunosuppressive effects of HIO factors by employing its proprietary screening and engineering technologies as well as diagnostic assays that can identify patients whose tumors produce HIO factors to advise physicians on therapeutic options. For more information, please visit www.navrogen.com . Nicholas C. Nicolaides, President & CEO Navrogen, Incorporated +1 610-399-2717 email us here Visit us on social media: LinkedIn Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

$Navrogen Granted Patent to Develop Antibodies That Are Refractory to Immunosuppressive Humoral Immuno-Oncology Factors$

免疫疗法抗体药物偶联物

2024-04-04

·PRNewswire

Navrogen Presents Its Anti-CD20 Antibody NAV-006 and ICAM-1 Refractory Antibody-Drug Conjugate Platform at the 2024 American Association for Cancer Research Annual Meeting

CHEYNEY, Pa., April 4, 2024 /PRNewswire/ -- Navrogen, Inc., a biopharmaceutical company specialized in developing therapies for cancer and immune-related disorders, will be presenting preclinical data on its next-generation anti-CD20 antibody, NAV-006, and ICAM-1 refractory antibody-drug conjugate platform at the 2024 American Association for Cancer Research (AACR) Conference in San Diego, California, on April 8-9. CD20-targeting rituximab antibody is the standard-of-care for non-Hodgkin's lymphoma (NHL). Recent clinical evidence suggests that high serum levels of the tumor-produced MUC16/CA125 protein has a negative impact on the efficacy of rituximab. To counteract the effects of CA125 binding to rituximab and reducing its tumor cell killing activity, Navrogen has generated a rituximab variant (NAV-006) using its BRITE proprietary technology. Navrogen will present data showing NAV-006's superior efficacy over rituximab in animal models of human NHL. Navrogen's screening technology has also found that CA125 inhibits other regulatory approved canonical and bispecific antibodies targeting CD19 and CD20 in relapsed/refractory NHL, underscoring a broader impact that CA125 has on biological drugs. "We are committed to combat cancers where humoral immunity is suppressed by CA125 and by other tumor-produced factors", said Dr. Luigi Grasso, Navrogen's Chief Scientific Officer. "Our BRITE-optimized NAV-006 offers a new therapeutic modality to treat lymphoma patients with high levels of CA125 in relapsed/refractory disease". Navrogen will also present the Humoral Immuno-Oncology (HIO) technology that has uncovered the tumor-produced protein ICAM-1, which binds to IgG1-type antibodies and inhibits their immune effector activity. "In addition to its immunosuppressive effects, we have found that membrane-bound ICAM-1 can reduce internalization of antibody-drug conjugates and their efficacy", continued Dr. Grasso. "We have engineered a trastuzumab-drug conjugate variant with superior cytotoxicity against ICAM-1 positive cancer cells. We are now building a portfolio of enhanced ADCs using this platform to advance internal as well as partnered ADC programs". About Navrogen™ Inc. Navrogen is a biotechnology company focused on the discovery of tumor-produced Humoral Immuno-Oncology (HIO) factors associated with suppressed humoral immunity and limited therapeutic response of immune-mediated therapies. The company's mission is to develop first-in-class agents that overcome the immunosuppressive effects of HIO factors via its proprietary screening and engineering technologies as well as diagnostic assays that can identify patients whose tumors produce HIO factors to advise physicians on therapeutic options. For more information, please visit . Contact: Steven Kyriakos VP Finance and Operations 610-399-2717 [email protected] SOURCE Navrogen, Inc.

AACR会议抗体药物偶联物免疫疗法

100 项与 Rituximab biobetter (Navrogen) 相关的药物交易

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