研究人员利用细菌与病毒组成抗癌联盟，突破免疫防御，精准靶向并安全摧毁癌细胞。图片来源：美国 《每日科学》网站 最新进展标志着该细菌-病毒联合系统向未来临床应用迈出了重要一步。研究团队正在更多类型的 肿瘤、小鼠模型、病毒及有效载荷中测试该方法的可行性，致力于开发一套能感知并响应细胞内特定条 件的病毒疗法工具包。他们还在探索将该系统与已在临床试验中证明安全的细菌菌株相结合的可能性。 研究团队表示，这一技术已在小鼠实验中验证有效，是首个实现细菌与抗癌病毒直接工程化合作的 范例，为开发多生物联合疗法奠定了基础。这类疗法有望实现单一微生物无法达成的治疗效果。 溶瘤病毒疗法是一种利用天然或经基因改造的病毒，特异性感染并摧毁癌细胞的治疗策略，尤其在 脑肿瘤领域显示出很强的潜力。然而，该疗法面临的一大挑战是人体自身的免疫防御机制。如果患者因 既往感染或疫苗接种已对病毒产生抗体，这些抗体就可能在病毒抵达肿瘤前将其清除。 研究团队通过把病毒"藏"进擅长追踪肿瘤的细菌中，成功规避了这一障碍。实验证明，细菌（部分 为鼠伤寒沙门氏菌）可用于投放溶瘤病毒，治疗那些对病毒已具备免疫能力的实体瘤。 美国哥伦比亚大学和洛克菲勒大学科学家利用细 ...

Core Viewpoint - The study identifies BRD9 as a key regulator of glioblastoma's resistance to oncolytic virus therapy, suggesting that inhibiting BRD9 can enhance the efficacy of such treatments [4][10]. Group 1: Research Findings - The research utilized a genome-wide CRISPR screening approach to discover that BRD9 is a critical factor in tumor resistance to oncolytic virus therapy [4][8]. - Inhibition of BRD9 significantly enhances the replication and anti-tumor effects of oncolytic herpes simplex virus type 1 (oHSV1), indicating a potential therapeutic value when combined with BRD9 inhibitors [6][10]. - BRD9 interacts with RELA to regulate the expression of antiviral genes, which is crucial for the effectiveness of oHSV1 therapy [7][8]. Group 2: Clinical Implications - The study suggests that BRD9 levels could serve as a potential biomarker for predicting clinical outcomes in oHSV1 therapy for glioblastoma patients [8][10]. - The findings highlight the importance of developing strategies to target BRD9 in order to overcome the resistance seen in glioblastoma treatments [10].

Core Viewpoint - Lepu Biopharma-B (02157) has regained market attention due to significant progress in its ADC pipeline, leading to a stock price increase of nearly 78% year-to-date, despite a previous decline since its IPO in 2022 [1][18]. Group 1: Company Overview - Lepu Biopharma was established in 2018 and has built its pipeline through acquisitions and partnerships, including PD-1 antibodies and ADC drugs [1]. - The company focuses on integrating PD-1 as a cornerstone for cancer treatment while developing ADCs and other therapies for enhanced clinical outcomes [1][12]. Group 2: Financial Performance - In 2024, Lepu Biopharma is projected to achieve revenue of 368 million RMB, a year-on-year increase of 63.21%, driven by the commercialization of PD-1 [4]. - Despite revenue growth, the company reported a loss of 424 million RMB in the same year, with cash reserves remaining stable at 401 million RMB [4]. Group 3: Pipeline Development - The core drug in Lepu's pipeline is MRG003, an EGFR-targeting ADC, which has shown promising results in clinical trials for nasopharyngeal carcinoma (NPC) and head and neck squamous cell carcinoma (HNSCC) [4][10]. - MRG003 has received breakthrough therapy designation from both the CDE and FDA, indicating its potential in treating difficult-to-manage cancers [10]. Group 4: Competitive Landscape - The global market for EGFR-targeting ADCs is competitive, with several companies, including Rakuten Medical and Systimmune, also developing similar therapies [6][7]. - Lepu's MRG003 has demonstrated superior efficacy compared to existing treatments, with an overall response rate (ORR) of 47.4% in NPC patients, significantly higher than the typical 20-30% ORR for second-line therapies [7][10]. Group 5: Future Prospects - The company is actively exploring combination therapies, such as MRG003 with PD-1, which has shown an ORR of 66.7% in early trials [12]. - Lepu is also advancing its CG0070 oncolytic virus therapy, which has shown promising results in treating non-muscle invasive bladder cancer (NMIBC) and has received breakthrough therapy designation from the FDA [14][15]. Group 6: Challenges Ahead - Despite the positive developments, Lepu Biopharma's reliance on external acquisitions for its pipeline raises questions about its internal R&D capabilities [18]. - The company faces challenges related to ongoing losses and the need for substantial funding to support its numerous clinical trials [18].