Avelumab

Neoadjuvant treatment with pepinemab appears to induce abundant, mature lymphoid structures that correlate with improved pathologic response. ROCHESTER, N.Y., May 27, 2025 (GLOBE NEWSWIRE) -- Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and Alzheimer’s disease (AD) through the inhibition of Semaphorin 4D (SEMA4D), today announced that it will present new data characterizing the unique mechanism of pepinemab to enhance immune responses to checkpoint therapies in the neoadjuvant setting that are associated with improved pathologic response in patients with head and neck cancer . Lead investigator and collaborator, Conor Steuer, MD from Winship Cancer Center at Emory University, will present results at the 2025 Annual Meeting of Clinical Oncology (ASCO) in Chicago on June 1, 2025 . ASCO Conference Information: Date: Sunday, June 1, 2025 Presentation title: Neoadjuvant biomarker trial of pepinemab to enhance nivolumab or ipilimumab activity in resectable head and neck cancer. Abstract 103. Time: 9:45-11:15 AM CST/10:45 AM – 12:15 PM EST. Session Title: Clinical Science Symposium – Turning “Cold” Tumors “Hot” Previously reported data from our collaboration with Emory University suggest a crucial role of pepinemab treatment in melanoma patients to facilitate immune cell interactions within highly organized and robust centers of immunity, called tertiary lymphoid structures, or TLS . By blocking the SEMA4D inhibitory signal to Dendritic Cells (DC), pepinemab allows productive, coordinated interactions between SEMA4D+ T cells, key effector cells capable of eradicating tumors, and DC, regulatory cells that promote immune cell interactions within TLS so as to amplify mature T cell responses. New data presented at ASCO will characterize the mechanisms of neoadjuvant treatment with pepinemab in patients with resectable head and neck cancer (HNSCC). Standard of care for these patients often involves toxic chemotherapy and/or radiotherapy, in addition to surgery, which can significantly impact their quality of life. Peri-operative treatment with immunotherapy has recently reported promising and potentially practice-changing results. Certain HNSCC with hot beds of immune cells organized into TLS have been shown to correlate with clinical benefit and positive response to immune checkpoint therapy. However, many HNSCC are considered immunologically “cold” tumors, due to exclusion of immune cells from tumor and/or high levels of immune suppressor cells, making them resistant to immune checkpoint therapy. Pepinemab has potential to be a major advance for HNSCC patients with cold and resistant disease , with capacity of a well-tolerated and effective treatment that can induce formation and harness the power of TLS to optimize the clinical benefit of immunotherapy. Our data demonstrate that the addition of pepinemab to neoadjuvant immune checkpoint treatments did not compound toxicities, yet it enhanced TLS maturity that correlated with improved pathologic response. Collectively, these results highlight the potential of pepinemab to turn immunologically cold tumors, such as HPV-negative head and neck cancer, into hot immune centers by inducing robust and mature TLS. About Pepinemab Pepinemab is a humanized IgG4 monoclonal antibody designed to block SEMA4D, which can otherwise bind to plexin-B1 receptors to trigger collapse of the actin cytoskeleton and lead to loss of homeostatic functions of dendritic cells in immune tissue and of astrocytes and other glial cells in the brain. Pepinemab appears to be well-tolerated with a favorable safety profile in multiple clinical trials in different cancer and neurological indications. About Vaccinex Inc. Vaccinex, Inc. is pioneering a differentiated approach to treating cancer and slowly progressive neurodegenerative diseases through the inhibition of semaphorin 4D (SEMA4D). The Company’s lead drug candidate, pepinemab, blocks SEMA4D, a potent biological effector that it believes prevents infiltration and activation of immune cells in tumors and triggers damaging inflammation in neurodegenerative diseases. In oncology, pepinemab is also being evaluated in combination with KEYTRUDA ® in the Phase 1b/2 KEYNOTE-B84 study in recurrent or metastatic head and neck cancer (HNSCC) and in combination with BAVENCIO ® in a Phase 1b/2 study in patients with metastatic pancreatic adenocarcinoma (PDAC). The oncology clinical program also includes several investigator-sponsored studies in solid tumors including breast cancer and melanoma. We believe pepinemab has also given promising results as a monotherapy in the Phase 1b/2 SIGNAL-AD study in Alzheimer’s Disease, and the Company has previously published promising Phase 2 data suggesting a slowing of cognitive decline in Huntington’s disease. Vaccinex has global commercial and development rights to pepinemab and is the sponsor of the KEYNOTE-B84 study which is being performed in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck and Co, Inc. Kenilworth, NJ, USA. Additional information about the study is available at: clinicaltrials.gov. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. BAVENCIO ® /avelumab is provided by Merck KGaA, Darmstadt, Germany, previously as part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany and Pfizer. Forward Looking Statements To the extent that statements contained in this press release are not descriptions of historical facts regarding Vaccinex, Inc. (“Vaccinex,” “we,” “us,” or “our”), they are forward-looking statements reflecting management’s current beliefs and expectations. Such statements include, but are not limited to, statements about our plans, expectations and objectives with respect to the results and timing of the KEYNOTE-B84 and SIGNAL-AD clinical trials; the use and potential benefits of pepinemab in R/M HNSCC, lung cancer, metastatic pancreatic adenocarcinoma (PDAC) and other indications; the potential for benefits as compared to single agent KEYTRUDA ® or BAVENCIO ® ; expectations with respect to the collaboration of Merck,; and other statements identified by words such as “anticipate,” “believe,” “plans,” “schedule,” “being,” “will,” “appears,” “expect,” “ongoing,” “potential,” “promising,” “suggest”, and similar expressions or their negatives (as well as other words and expressions referencing future events, conditions, or circumstances). Forward-looking statements involve substantial risks and uncertainties that could cause the outcome of our research and pre-clinical development programs, clinical development programs, future results, performance, or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, uncertainties inherent in the execution, cost and completion of preclinical studies and clinical trials, that interim and preliminary data may not be predictive of final results and does not ensure success in later clinical trials, uncertainties related to regulatory approval, risks related to our dependence on our lead product candidate pepinemab, and other matters that could affect our development plans or the commercial potential of our product candidates. Except as required by law, the Company assumes no obligation to update these forward-looking statements. For a further discussion of these and other factors that could cause future results to differ materially from any forward-looking statement, see the section titled “Risk Factors” in our previous reports filed with the Securities and Exchange Commission and the other risks and uncertainties described in the Company’s 2024 year-end Form 10-K filed with the SEC. Investor Contact Elizabeth Evans, PhD Chief Operating Officer Senior Vice President, Vaccinex, Inc. (585) 271-2700 eevans@vaccinex.com 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.

摘要：本文聚焦噬菌体展示技术在抗癌抗体发现中的应用。先介绍该技术的发展及在癌症治疗中的重要性，接着阐述噬菌体展示技术的原理，包括不同噬菌体类型、展示价态、抗体库构建与筛选等；随后说明基于此技术的抗体工程改造方法；最后列举通过该技术获得的抗癌治疗性抗体，并展望其未来在癌症治疗领域的发展潜力，表明该技术有望为癌症治疗带来重大突破。一、癌症治疗与噬菌体展示技术概述癌症长期以来都是难以攻克的疾病，多年来，多种治疗方式不断涌现，如手术切除、放疗、化疗以及免疫治疗等（图 1）。随着医学发展，基于抗体和抗体 - 药物偶联物（ADCs）的靶向免疫治疗，凭借疗效高、毒性相对较低的优势，成为抗癌的重要手段。目前，鉴定具有治疗活性抗体的主要技术有杂交瘤平台、单个 B 细胞分离以及噬菌体/酵母展示。其中，噬菌体展示技术由 George P. Smith 教授于 1985 年提出，2018 年，该技术的相关研究获得诺贝尔化学奖，它极大地推动了蛋白质/抗体工程和药物发现领域的发展。尽管技术不断进步，但寻找新的抗癌靶向抗体和治疗靶点仍是研究重点。二、噬菌体展示技术详解2.1 噬菌体类型M13 噬菌体：属于 F 特异性丝状噬菌体，在细菌宿主（如大肠杆菌）中繁殖时不杀死宿主，其基因组为正链环状单链 DNA。M13 噬菌体的衣壳由 5 种蛋白质组成，基于 M13 的平台是噬菌体展示中最常用的（图 4）。其他噬菌体：T4 噬菌体基因组为线性双链 DNA，能展示大蛋白且宿主范围广；T7 噬菌体对极端条件抗性强；λ - 噬菌体的某些蛋白可用于融合展示；RNA 大肠杆菌噬菌体 Qβ 能高效展示小蛋白和肽，其高突变率利于文库多样化和亲和力成熟。2.2 展示价态展示价态是选择噬菌体展示平台的重要考虑因素。以 M13 为例，将文库与 pVIII 融合可实现多价展示，适合展示肽和小蛋白，利于筛选低亲和力结合物；与 pIII 融合则为单价展示，更适合较大的蛋白质，如抗体片段，有助于筛选高亲和力结合物 。2.3 抗体库抗体库的大小和组成至关重要。早期常从外周血、扁桃体或脾脏等分离的 B 细胞获取抗体编码序列构建文库，免疫后的宿主来源文库更易筛选到理想抗体。如今，大规模平行寡核苷酸合成技术可增加文库多样性，控制抗体特征，提高筛选效率。2.4 抗体筛选基本流程：通过亲和筛选（又称生物淘选）从噬菌体表面展示的数十亿抗体变体中鉴定抗体片段。先构建抗体文库，转化为噬菌体形式后，在固相支持物上与目标进行多轮筛选，包括阳性和阴性选择，最后对筛选出的噬菌体进行扩增和分析（图 5）。筛选策略：可使用患者样本、癌细胞系、重组蛋白等作为目标材料，也可进行体内筛选。此外，还有多种先进策略可用于筛选具有特定性质的抗体，如能内吞、pH 依赖结合、识别特定表位等。三、基于噬菌体展示的抗体工程3.1 常见抗体格式治疗性抗癌抗体的常见形式是免疫球蛋白 G（IgG），但因其结构复杂无法在噬菌体表面展示。在噬菌体展示中，常使用更紧凑的抗体片段，如单链可变片段（scFv）、Fab 片段、单域抗体（sdAb）等 （图 6）。这些片段虽稳定性较好，但临床应用受限，常需进一步工程改造。3.2 抗体人源化为降低抗体免疫原性，临床主要研究人源化或全人源抗体。抗体人源化通过框架替换或互补决定区（CDR）移植，将非人源抗体改造得更接近人源抗体，并通过噬菌体文库筛选保留其特异性和亲和力。3.3 亲和力成熟通过体外/体内诱变或基因合成，对抗体进行多轮改造和筛选，提高抗体与目标的结合强度。3.4 抗体成药性从噬菌体展示中分离的高亲和力抗体不一定具有治疗可行性，需考虑其折叠、稳定性、翻译后修饰等特性。可通过重新格式化抗体或去除不良序列，筛选具有良好成药性的抗体。四、噬菌体展示技术获得的抗癌治疗性抗体利用噬菌体展示技术已成功开发出多种抗癌治疗性抗体，部分已获 FDA 批准，部分处于临床试验阶段（表 2）。这些抗体靶向多种癌症相关抗原，在癌症治疗中展现出巨大潜力。例如，阿替利珠单抗（Atezolizumab）和阿维鲁单抗（Avelumab）作为检查点抑制剂已获批；尼妥珠单抗（Necitumumab）用于治疗头颈癌和非小细胞肺癌；雷莫西尤单抗（Ramucirumab）可用于治疗胃癌和非小细胞肺癌等 。五、结论与展望噬菌体展示技术在抗癌抗体的发现和开发中具有重要价值，其能够筛选高特异性和高亲和力的抗体，部分抗体已在临床研究中取得良好效果。随着新的展示平台出现和抗体工程技术进步，噬菌体展示技术在抗癌治疗领域的应用有望进一步拓展，为癌症患者带来新的希望。识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。