撰文丨王聪 编辑丨王多鱼 排版丨水成文 2025 年 诺贝尔生理学或医学奖 授予了 Mary Brunkow 、 Fred Ramsdell 、 坂口志文 （ Shimon Sakaguchi ） ，他们发现并定义了 调节性 T 细胞 （Treg 细 胞） ，揭示了其在控制自身反应性响应中的重要性，开创了 Treg 细胞介导的 外周免疫耐受 这一新领域。 1995 年， 坂口志文 在 The Journal of Immunology 期刊发表论文 ，发现了 一种 此前未知的 T 细胞类型 （表达 CD4 和 CD25 的 T 细胞） ，这类细胞能保护 身体免受自身免疫疾病的侵害。2001 年， Mary Brunkow 、 Fred Ramsdell 在 Nature Gentices 期刊发表了三篇论文 ，在小鼠中人类中发现， Foxp3 基因突 变会导致自身免疫疾病。2003 年， 坂口志文 将这些发现联系起来，在 Science 期刊发表论文， 证明了 Foxp3 基因控制着他于 1995 年所发现的免疫细胞 （即 Treg 细胞） 的发育， 这些 Treg 细胞监控其他免疫细胞，并确保我们的免疫系统 ...

Core Insights - The 2025 Nobel Prize in Physiology or Medicine was awarded to three scientists for groundbreaking discoveries in regulatory T cells, revealing how the immune system maintains self-balance through "peripheral immune tolerance," which is crucial for understanding autoimmune diseases and developing new cancer immunotherapy strategies [4][5] - Traditional animal models struggle to accurately simulate the human immune system due to species differences, leading to challenges in mechanism research, clinical translation, and model construction [4] - Humanized immune system mice provide a key technology to address these issues, allowing for effective preclinical evaluation of candidate drugs, significantly reducing subsequent development risks, and providing a reliable platform for assessing new cell therapies and bispecific antibodies [5] Course Overview - An online course titled "Applications of Humanized Immune System Mice in Tumor Immunity and Autoimmune Diseases" will be held on October 21, featuring Dr. Yu Jing, a senior scientist at Saiye Bio, focusing on scientific decision-making for obtaining valuable experimental data [5][7] - The course will cover the following topics: 1. Advances in tumor immunity: Translating Nobel-level discoveries into new treatment strategies and related research dynamics [7] 2. Model development history: Reviewing the evolution of models and the characteristics and applicable scenarios of PBMC, HSC, and other construction strategies [7] 3. Optimization strategies and application cases: Emphasizing research on tumor immunity and autoimmune diseases, drug efficacy, and safety evaluation [7] 4. Interactive session: The lecturer will answer common questions related to disease research [7] Research Applications - The huHSC-C-NKG-ProF model has been utilized in significant research, including: 1. CAR-T cell therapy for solid tumors, revealing how Foxp3 regulates CAR-T cell metabolism to enhance treatment efficacy [12] 2. Liver cancer immune evasion studies, identifying ETV5 as a potential biomarker for prognosis and a target for new treatment strategies [12] - Saiye Bio's humanized immune system mice, particularly the huHSC-C-NKG-ProF model, can reconstruct various human immune cells, providing a robust platform for research [13][14] Product Offerings - Saiye Bio offers several humanized immune system models, including: - huHSC-C-NKG-ProF: Full immune system reconstruction with a humanization rate of 40-60% after 8 weeks [16] - huHSC-C-NKG-ProM: Reconstructs lymphoid T and B cells with a similar humanization rate [16] - huHSC-C-NKG-ProN: Focuses on T, B, and NK cells with minimal myeloid development [16] - huHSC-C-NKG: Supports long-term presence of human cells with a lifespan exceeding one year [16] - huPBMC-C-NKG: Primarily reconstructs lymphoid T cells with a fast reconstruction speed [16]

Group 1 - The 2025 Nobel Prize in Physiology or Medicine was awarded to Mary E. Brinco, Fred Ramsdell, and Shizuo Sasakawa for their discovery of key pathways regulating the immune system, which is crucial for understanding autoimmune diseases like type 1 diabetes, rheumatoid arthritis, and lupus [2][8] - The Nobel Prize is recognized globally as a top honor, celebrating outstanding achievements in various fields including medicine, physics, chemistry, literature, economics, and peace [2] - The announcement of the winners often comes as a surprise, with some recipients being unaware until they are contacted by the Nobel Prize committee [3][4] Group 2 - The Nobel Prize committee successfully contacted all three chemistry award winners before the official announcement for the first time on October 8 [5] - The process of informing winners can be dramatic, as illustrated by the experiences of Brinco and Ramsdell, who were both in unexpected situations when they received the news [6][11] - The winners' reactions varied, with some initially doubting the news or mistaking the calls for telemarketing [10][13]

Core Insights - The Nobel Prize in Physiology or Medicine in 2025 is expected to recognize groundbreaking discoveries in "peripheral immune tolerance," highlighting the development potential of Treg in autoimmune diseases, cancer, and immune rejection [1] - The main challenge in Treg-targeted therapies is selectivity, requiring drugs to accurately differentiate between harmful Tregs in tumors and beneficial Tregs in peripheral tissues [1] Group 1: Treg Therapy Development - Development strategies include enhancing tumor tissue permeability, strengthening ADCC effects, or targeting higher expression markers in tumor-infiltrating Tregs [1] - Several global biotechnology companies are engaged in developing related therapies, with Chinese companies like Cellin Biotech and Binosi Biotech focusing on Treg treatments for diseases such as ALS and rheumatoid arthritis [1] Group 2: Cancer and Autoimmune Disease Treatment - New cancer therapies aim to inhibit Treg activity in tumor regions, allowing the immune system to effectively attack tumors [1] - Autoimmune diseases may be treated by enhancing Treg functionality, while organ transplants could benefit from increased Treg levels to reduce rejection responses [1] Group 3: Biopharmaceutical ETF - The biopharmaceutical ETF (512290) tracks the CS Biomedicine Index (930726), which selects listed companies in biotechnology, pharmaceuticals, and medical devices from the Shanghai and Shenzhen markets [1] - The CS Biomedicine Index reflects the overall performance of listed companies in the biopharmaceutical sector, focusing on companies with strong competitiveness in relevant fields, showcasing industry growth and innovation capabilities [1]

Investment Rating - The report does not explicitly state an investment rating for the industry [2]. Core Insights - The pharmaceutical and biotechnology sector experienced a slight increase of 0.4% from September 29 to October 10, underperforming compared to the Wind All A index (1.63%) and the CSI 300 index (1.47%) [3][8]. - Key segments leading the gains include hospitals (2.29%), medical devices (2.29%), and vaccines (2.08%), while chemical preparations (-1.41%), offline pharmacies (-0.68%), and raw materials (-0.38%) lagged behind [3][8]. - The report highlights the upcoming ESMO conference from October 17 to 21, 2025, in Berlin, emphasizing the importance of domestic innovative drug companies such as Kangfang Biotech, Kelun-Botai, and others, particularly in the dual antibody and ADC technology platforms [3][8]. - A significant outbreak of Chikungunya fever was reported in Guangdong Province, with 3,181 new local cases from September 28 to October 4, 2025, indicating a need for effective diagnostic tools [3][8]. Market Weekly Review - The pharmaceutical and biotechnology sector rose by 0.4% from September 29 to October 10, underperforming the Wind All A index (1.63%) and the CSI 300 index (1.47%) [8]. - The best-performing sub-sectors included hospitals (2.29%), medical devices (2.29%), and vaccines (2.08%), while the worst performers were chemical preparations (-1.41%), offline pharmacies (-0.68%), and raw materials (-0.38%) [8][9]. - Notable individual stock performances included Zhendemedical (31.82%), Wanbangde (21.2%), and Changshan Pharmaceutical (12.88%) for gains, while Nanjing Pharmaceutical (-28.67%), Fudan-Zhangjiang (-13.64%), and Nuocheng Jianhua-U (-12.94%) faced significant declines [11]. Industry News and Key Company Announcements - The report mentions significant events such as the agreement between the U.S. government and AstraZeneca to reduce drug prices in exchange for tariff relief [12]. - The announcement of the 2025 Nobel Prize in Physiology or Medicine awarded for discoveries related to peripheral immune tolerance, which may lead to new therapies for autoimmune diseases and cancer [12]. - The report also covers various company announcements, including Novo Nordisk's acquisition of Akero Therapeutics for $5.2 billion, and the approval of clinical trials for several new drugs [15][17].

Investment Rating - The report maintains a strong confidence in the pharmaceutical sector's potential for a reversal in 2025, particularly focusing on innovative drugs and the recovery of left-side sectors as the biggest investment opportunities for the year [5][14]. Core Insights - The innovative drug sector is expected to continue its upward trend, with BD (business development) activities anticipated to catalyze market movements. The upcoming ESMO conference (October 17-21) is highlighted as a key event for clinical data disclosures from domestic innovative drug companies [2][13]. - The report emphasizes the importance of recent Nobel Prize discoveries related to peripheral immune tolerance, which are relevant to the development of new therapies in oncology and autoimmune diseases. This underscores the significance of innovation in these fields [40][50]. - The report notes that the CXO industry in China is entering a recovery phase, with improvements expected in industry orders, capacity utilization, and performance metrics due to enhanced domestic investment and financing data [2][5]. Summary by Sections Innovative Drugs - The innovative drug sector has seen a recent pullback, but the long-term upward trend remains intact. The report suggests that the market is awaiting further BD catalysts and highlights the importance of upcoming clinical data from the ESMO conference [2][13]. - The report indicates that the overall sentiment in the innovative drug sector is still positive, with a focus on potential breakthroughs in cancer and autoimmune therapies following the recent Nobel Prize discoveries [40][50]. Biologics - Novo Nordisk announced an agreement to acquire Akero for $4.7 billion, with Akero's FGF21 analog EFX showing promise as a leading therapy for metabolic dysfunction-related fatty liver disease (MASH) [3][51]. - The report suggests that EFX is the only drug in Phase 2 trials demonstrating significant fibrosis regression in F4 patients, highlighting the need for continued attention to developments in this area [51][57]. Medical Devices - The commercialization of innovative products is accelerating, with domestic replacements making significant progress. For instance, MicroPort's Tumi laparoscopic surgical robot has surpassed 100 global orders and is leading the domestic market share [4][58]. - The report notes that the Tumi robot has received market access in over 60 countries and regions, with a strong presence in high-end markets such as Europe [60][62]. Traditional Chinese Medicine - There has been a continuous increase in new drug IND and NDA applications for traditional Chinese medicine, with 92 new IND applications and 42 NDA applications reported in the first nine months of 2025 [3][64]. - The report highlights ongoing policy support for traditional Chinese medicine, which is expected to drive further innovation and development in this sector [64][65].

Core Insights - The article discusses the role of regulatory T cells in the immune system, highlighting their importance in preventing autoimmune diseases and maintaining immune tolerance [1][5][14] Group 1: Immune System Functionality - The immune system distinguishes between self and non-self cells, with regulatory T cells acting as mediators to suppress overactive immune responses [1][5] - T cells possess unique receptors that allow for the identification of a vast array of pathogens, theoretically generating over 10^15 different T cell receptors [5][7] Group 2: Research Breakthroughs - The Nobel Prize winners identified regulatory T cells as crucial for peripheral immune tolerance, addressing gaps in previous research on immune regulation [7][12] - The discovery of the Foxp3 gene as essential for the development and function of regulatory T cells has significant implications for understanding autoimmune diseases [12][14] Group 3: Medical Implications - Potential new medical treatments based on regulatory T cell mechanisms are currently in clinical trials, targeting cancer therapies and autoimmune disease treatments [14] - Strategies include enhancing regulatory T cell formation to prevent organ transplant rejection and using engineered T cells to modulate immune responses [14]

Investment Rating - Industry Rating: Outperform the Market (maintained rating) [5] Core Insights - The 2025 Nobel Prize in Physiology or Medicine was awarded for groundbreaking discoveries in "peripheral immune tolerance," highlighting the development potential of regulatory T cells (Treg) in autoimmune diseases, cancer, and organ transplantation [1][2] - Key research findings include the identification of Treg cells by Shimon Sakaguchi in 1995 and the discovery of the FOXP3 gene's role in Treg development and function by Mary E. Brunkow and Fred Ramsdell in 2001 [2] - The "peripheral immune tolerance" mechanism offers therapeutic avenues for various diseases, including enhancing Treg function for autoimmune diseases, inhibiting Treg activity in cancer to allow immune system attacks on tumors, and improving organ transplant acceptance [3] Summary by Sections - **Therapeutic Development**: Multiple therapies targeting the Treg mechanism are currently undergoing clinical validation, with companies like RegCell and Sonoma Biotherapeutics founded by the awarded scientists focusing on Treg therapies [4] - **Market Opportunities**: Chinese companies such as Cellin Biotech and Bionautics are also entering this field, targeting diseases like amyotrophic lateral sclerosis and rheumatoid arthritis through Treg therapies [4] - **Targeted Therapy Challenges**: The main challenge in Treg-targeted therapies is selectivity, requiring drugs to distinguish between harmful tumor-infiltrating Tregs and beneficial peripheral Tregs [4] - **Investment Recommendations**: Companies to watch include Lixin Pharmaceutical (CCR8 antibody LM-108), Kangyuan Pharmaceutical (CCR8 antibody KYS2301), and others developing CTLA-4 and CCR8 antibodies [5]

Core Viewpoint - The article discusses the significance of the 2025 Nobel Prize in Physiology or Medicine awarded to Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking work on regulatory T cells (Treg cells) and their role in immune tolerance, which has profound implications for understanding autoimmune diseases and cancer escape mechanisms [3][35]. Group 1 - The Nobel Prize was awarded for the discovery and definition of CD4+ CD25+ FOXP3+ regulatory T cells (Treg cells) and their importance in controlling self-reactive responses, marking a new field of research in peripheral immune tolerance [3][35]. - The research highlights the collaborative effort and curiosity in science, leading to a transformative understanding of immune regulation [3][35]. - The findings have significant implications for the treatment of autoimmune diseases and cancer, emphasizing the potential of Treg cells in clinical applications [35]. Group 2 - Mary Brunkow expressed her surprise at receiving the Nobel Prize, reflecting on the teamwork involved in their research and the changes in her scientific career since then [14][24]. - Fred Ramsdell shared a humorous account of how he learned about his award while camping, illustrating the unexpected nature of the recognition [23][24]. - Shimon Sakaguchi emphasized the importance of persistence in research, stating that the discovery of Treg cells was a result of continuous exploration despite challenges in the field [33][35]. Group 3 - The article highlights the collaboration between biotechnology and academic sectors, showcasing how such partnerships can lead to significant advancements in medical treatments [29][30]. - The historical context of the research is noted, with the original findings based on a mutant mouse model that exhibited severe autoimmune phenotypes, underscoring the importance of foundational research [30][31]. - The recognition of their work is seen as a motivation for further exploration and application of Treg cells in treating various immune diseases and improving organ transplant outcomes [35].

Core Viewpoint - The announcement of the Nobel Prize in Physiology or Medicine is expected to stimulate the development of Treg cell therapy and innovative drug research, benefiting companies like HAPO Pharmaceuticals [1] Company Summary - HAPO Pharmaceuticals-B (02142) saw its stock price rise over 8% in early trading, currently up 6.3% at HKD 16.36, with a trading volume of HKD 58.26 million [1] - The company is developing a next-generation antibody HBM4003 targeting the CTLA-4 pathway, which has shown excellent safety characteristics in clinical studies and demonstrated clear efficacy signals in multiple tumor types, including colon cancer, liver cancer, and neuroendocrine tumors [1] - HAPO's antibody HBM1022, targeting the CCR8 pathway, is considered a highly promising candidate in its pipeline, potentially leading to breakthroughs in tumor immunotherapy [1]