Vopratelimab

在人体复杂的免疫系统中，存在着许多关键的调控分子，它们如同精密的开关，指挥着免疫细胞的“进与退”。其中，CD278（也被称为ICOS）是一个备受关注的靶点。它不仅是T细胞活化的“精准开关”，更在维持免疫平衡中扮演着重要角色。虽然目前全球尚无靶向CD278的上市药物，但其在临床研究中的潜力正逐步显现。今天，我们就来深入了解一下这位免疫界的“精密导航员”。 🔬 CD278的作用机制：T细胞的“精准导航员” CD278属于免疫球蛋白超家族，其基因定位于人类染色体2q33.2。它与我们熟知的CD28、CTLA-4同属一个家族，但功能却各有侧重。CD278最大的特点是“诱导性表达”——它几乎不在静息的T细胞上表达，而是在T细胞被激活后才迅速上调。 当抗原呈递细胞上的配体（ICOSL）与CD278结合后，会启动下游的PI3K-AKT、NF-κB等信号通路。这就好比给已经出发的T细胞注入了“强心剂”，不仅促进了T细胞的增殖和分化，还特别支持滤泡辅助性T细胞（Tfh）的发育。Tfh细胞对于B细胞产生抗体至关重要，因此，CD278在体液免疫应答中起到了承上启下的核心作用。 💊 研发现状：激动剂与拮抗剂的“双轨并行” 目前，靶向CD278的药物研发正处于临床探索的黄金期，主要分为“激动剂”和“拮抗剂”两条路径，旨在通过不同机制调节免疫系统。 一方面，激动剂旨在“踩油门”。例如葛兰素史克研发的GSK3359609，以及Jounce Therapeutics开发的Vopratelimab（JTX-2011），它们通过激活CD278信号通路，增强效应T细胞的功能，主要用于解决免疫功能低下或慢性感染等问题。 另一方面，拮抗剂则负责“踩刹车”。阿斯利康开发的MEDI-570和ICOS/CD28双特异性抗体Acazicolcept，通过阻断CD278与其配体的结合，抑制过度活跃的T细胞反应，从而治疗自身免疫性疾病。目前，单一靶点药物的疗效仍有提升空间，因此临床研究更多倾向于“联合治疗”，例如将CD278药物与抗PD-1或抗CTLA-4抗体联用，以期通过多通路协同达到更好的治疗效果。 🚀 未来趋势：从精准医疗到应用拓展 随着抗体工程技术的进步，CD278靶点的研究正向着更精准、更安全的方向发展。 首先，精准化治疗将成为主流。未来的研发将不再“一刀切”，而是通过检测患者体内的生物标志物（如CD278表达水平、T细胞亚群比例），筛选出最可能获益的人群，实现个性化治疗。 其次，药物形式将更加多元化。除了传统的单克隆抗体，科学家们正在开发双特异性抗体（如同时靶向CD278和PD-1）以及小分子调节剂，这不仅能提升疗效，还能通过口服等方式提高患者的用药依从性。 最后，应用场景将进一步拓宽。除了目前聚焦的免疫相关疾病，CD278靶向药物在慢性炎症、移植排斥反应以及某些感染性疾病的治疗中，也展现出了广阔的应用前景。 💡 总结与服务支持 综上所述，CD278作为调控T细胞效应阶段的核心分子，以其独特的“诱导性表达”机制，成为了免疫治疗领域极具潜力的研究方向。从基础的机制探索到药物研发，每一步都离不开精准的实验数据支持。如果你正在进行CD278相关的科研攻关，卡梅德生物可以提供靶点验证、抗体筛选、细胞模型构建等相关技术服务，助力你的研究从理论走向实践，共同推动免疫治疗领域的发展。

CAMBRIDGE, MA, USA I March 27, 2023 I Jounce Therapeutics, Inc. (NASDAQ: JNCE) (“Jounce” or the “Company”), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, today announced it has entered into a definitive merger agreement whereby Concentra Biosciences, LLC (“Concentra”) will acquire Jounce for $1.85 in cash per share plus a non-tradeable contingent value right (the “CVR”). The $1.85 per share upfront consideration represents a premium of approximately 75% to Jounce’s closing share price immediately prior to the March 14, 2023 public disclosure of Concentra’s acquisition proposal. Following a thorough review process conducted with the assistance of its legal and financial advisors, Jounce’s Board of Directors has determined that the acquisition by Concentra – of which Tang Capital Partners, LP is the controlling shareholder – is in the best interests of all Jounce shareholders, and has unanimously approved the merger agreement. Jounce’s Board of Directors is no longer recommending the proposed all-share merger transaction (the “Redx Business Combination”) with Redx Pharma Plc (AIM:REDX) (“Redx”). The Jounce Board of Directors has notified Redx of the withdrawal of its recommendation in favor of the Redx Business Combination and termination of the co-operation agreement dated February 23, 2023 between Jounce and Redx. In conjunction with the merger agreement, Jounce is implementing a workforce reduction of approximately 84% of its employees. This reduction is expected to be completed within the next month and Jounce will incur restructuring costs totaling approximately $6.5 million 1 . The remaining Jounce employees will work to complete the sale of the Company, conduct activities to maximize the value of the CVR, work to ensure that patients on the SELECT and INNATE trials have the opportunity to continue receiving therapy with vopratelimab, JTX-8064 and pimivalimab and to otherwise ensure a smooth transition to Concentra. Pursuant and subject to the terms of the merger agreement, a subsidiary of Concentra will commence a tender offer by April 7, 2023 to acquire all outstanding shares of Jounce for $1.85 in cash per share at closing plus a non-tradeable CVR representing the right to receive 80% of the net proceeds payable for a period of ten years post-closing from any license or disposition of Jounce’s programs effected within two years of closing and 100% of the potential aggregate value of certain specified potential cost savings. Closing of the tender offer is subject to certain conditions, including the tender of Jounce shares representing at least a majority of the total number of outstanding shares as of immediately following the consummation of the offer; the availability of at least $110 million of cash and cash equivalents, net of any tail and closing costs, at closing, and other customary conditions. The acquisition is expected to close in the second quarter of 2023. About Jounce Therapeutics Jounce Therapeutics, Inc. is a clinical-stage immunotherapy company dedicated to transforming the treatment of cancer by developing therapies that enable the immune system to attack tumors and provide long-lasting benefits to patients through a biomarker-driven approach. Jounce currently has multiple development stage programs ongoing while simultaneously advancing additional early-stage assets from its robust discovery engine based on its Translational Science Platform. For more information, please visit www.jouncetx.com. SOURCE: Jounce Therapeutics