撰文丨王聪 编辑丨王多鱼 排版丨水成文 在我们身体的每个细胞里，时刻都在进行着一场静默的"暗战"——细胞中的 RNA，有时会形成一些类似病 毒 RNA 的双链 RNA （dsRNA） 结构，如果它们被免疫系统误判为"外敌入侵"，就会引发可怕的自身免 疫风暴。防止这场灾难发生的关键，是一个名为 ADAR1 的蛋白质。 然而， ADAR1 有着 两面性 ， 它不只是发挥着维持体内免疫平衡 以防止自身免疫疾病的作用，还发挥着 促进癌症进展、免疫逃逸和治疗耐药性的作用。 近日，Cell Press 旗下综述期刊 Trends in Cell Biology 发表了来自牛津大学的题为： ADAR1: from basic mechanisms to inhibitors 的综述论文，该综述系统梳理了 ADAR1 的最新研究进展，解读了其两面 性—— ADAR1 的缺失会导致自身免疫疾病，而其表达会促进癌症的发展和转移，该综述还探讨了 ADAR1 对人类疾病的意义——开发 ADAR1 抑制剂用于癌症治疗。 如果 ADAR1 （尤其是 p150 亚型） 功能失常，后果是灾难性的。研究表明，无论是人类还是小鼠，细胞 中 AD ...

CD8⁺ T 细胞 是机体抗肿瘤与抗病毒免疫反应的核心效应细胞 ， 在肿瘤微环境或慢性感染中，长期抗原刺 激会使 CD8⁺ T 细胞逐渐进入耗竭状态 ， 同时其表观基因组也会发生广泛变化。然而，高级染色质空间结 构是否以及如何参与耗竭 CD8⁺ T 细胞 分化，目前尚不清楚。 2025 年 11 月 18 日，西湖大学医学院 董晨 院士 团队 （ 李瑞风 、 危琨 为共同第一作者 ） 在 Nature Immunology 期刊 发表了题为： Analysis of the three-dimensional genome of exhausted CD8⁺ T cells reveals a critical role of IRF8 in their differentiation and functions in cancer 的研究论文。 该研究构建了肿瘤特异性耗竭 CD8⁺ T 细胞的染色质空间结构图谱，揭示了转录因子 IRF8 通过招募结构蛋 白 CTCF 重塑染色质空间结构、调节基因表达，进而调控耗竭 CD8⁺ T 细胞分化及抗肿瘤功能。该研究为 理解肿瘤耗竭 CD8⁺ T 细胞分化机制提供了新 ...

Core Viewpoint - Cancer immunotherapy is emerging as a key treatment method for cancer, following surgery, radiotherapy, and chemotherapy, and is expected to see significant market growth in the coming years [1][6][7]. Group 1: Industry Definition and Classification - Cancer immunotherapy aims to activate or enhance the immune system to target tumor cells, utilizing methods such as cytokine therapy, cancer vaccines, T-cell therapy, and immune checkpoint inhibitors [2][4]. Group 2: Current Development Status - Cancer remains a leading health threat, with over 10 million deaths annually. The global anti-cancer drug market is projected to grow from $150.3 billion in 2020 to $253.3 billion in 2024, with cancer immunotherapy expected to reach $69.91 billion, accounting for 27.60% of the market [4][6][7]. Group 3: Industry Chain - The cancer immunotherapy industry chain includes upstream activities such as basic research and drug design, midstream development and production, and downstream medical institutions and testing agencies [8]. Group 4: Development Environment and Policies - Cancer is the leading cause of death globally, with a low early diagnosis rate in China. The government has implemented policies to enhance cancer prevention and treatment, such as the "Healthy China Action - Cancer Prevention and Control Action Implementation Plan (2023-2030)" [9]. Group 5: Competitive Landscape - The cancer immunotherapy market is characterized by concentrated leadership and technological differentiation, with key players including Legend Biotech, Akeso, I-Mab, Junshi Biosciences, and others. Notable advancements have been made in CAR-T, bispecific antibodies, and NK therapies [10][11]. Group 6: Future Development Directions - While cancer immunotherapy has transitioned from laboratory concepts to clinical practice, challenges such as resistance, toxicity, and accessibility remain. Future advancements may lead to a shift from "prolonging survival" to "functional cure" through interdisciplinary innovation and policy support [12][13].

Core Viewpoint - The study identifies TRAP1 as a mitochondrial chaperone that is suppressed by cancer, leading to immune evasion, and suggests that restoring TRAP1 can reprogram tumor-associated macrophages (TAM) to enhance anti-tumor immunity, positioning the TRAP1 pathway as a promising new target for cancer immunotherapy [2][9]. Group 1 - TRAP1 is a mitochondrial HSP90 molecular chaperone that acts as a metabolic checkpoint, inhibiting oxidative respiration and limiting the suppressive function of macrophages [5]. - In the tumor microenvironment, TRAP1 expression is downregulated through the TIM4-AMPK signaling pathway, and its absence enhances immune suppressive activity while promoting tumor immune evasion [6]. - Inhibition of TRAP1 increases electron transport chain activity and raises the ratio of α-ketoglutarate to succinate, reshaping mitochondrial homeostasis and leading to enhanced immune suppression through JMJD3-mediated histone demethylation [6]. Group 2 - Targeting TIM4 and JMJD3 to restore TRAP1 can reprogram TAM, disrupt the immune evasion of the tumor microenvironment, and enhance anti-tumor immunity [7]. - The findings establish TRAP1 as a key regulatory factor integrating metabolic and epigenetic control of suppressive TAM functions, highlighting the TRAP1 pathway as a promising new target for cancer immunotherapy [9].

Group 1 - The company has successfully completed the first patient dosing in the IB/II clinical trial of IMM2510 in combination with IMM01 for the treatment of advanced solid tumors, marking a significant milestone in innovative cancer immunotherapy [1] - IMM2510, developed by the company, is a bispecific molecule targeting VEGF and PD-L1, designed to inhibit angiogenesis, reduce tumor size, and enhance immune response sensitivity [1] - The mechanism of IMM2510 includes blocking the PD-L1/PD-1 interaction and inducing antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP), activating T cells, natural killer cells, and macrophages [1] Group 2 - The company has entered into a licensing and collaboration agreement with Axion Bio, Inc., granting the company commercialization rights for IMM2510 in Greater China while allowing Axion Bio, Inc. exclusive rights for research, development, and commercialization outside Greater China [2] - The company's core product, IMM01, is the first SIRPα-Fc fusion protein to enter clinical stages in China, designed to activate macrophages by blocking the "don't eat me" signal and delivering the "eat me" signal [3] - IMM01 has received orphan drug designation from the FDA for first-line treatment of CMML in combination with azacitidine, demonstrating its potential in the market [3] - The company holds global intellectual property and commercialization rights for IMM01, with a patent family that includes granted patents in China, the US, Japan, and the EU [3]

Group 1 - Company has successfully completed the first patient dosing in the Phase IB/II clinical trial of IMM2510 in combination with IMM01 for the treatment of advanced solid tumors, marking a significant milestone in the field of innovative cancer immunotherapy [1] - IMM2510 (Perivalephap α) is a proprietary dual-specific molecule targeting Vascular Endothelial Growth Factor (VEGF) and Programmed Cell Death Ligand 1 (PD-L1), designed to inhibit angiogenesis, reduce tumor size, and enhance tumor cell sensitivity to immune responses [1] - The mechanism of IMM2510 includes blocking the PD-L1/Programmed Cell Death Protein 1 (PD-1) interaction and inducing Fc-mediated Antibody-Dependent Cellular Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP) to activate T cells, natural killer cells, and macrophages [1] Group 2 - The company has entered into a licensing and collaboration agreement with Axion Bio, Inc., granting the company commercialization rights for IMM2510 in Greater China while allowing Axion Bio, Inc. exclusive rights for research, development, and commercialization outside Greater China [2] - The core product IMM01 (Tidapepac) is an innovative molecule targeting CD47, recognized as the first SIRPα-Fc fusion protein to enter clinical stages in China, demonstrating a dual mechanism to activate macrophages [3] - IMM01 has received orphan drug designation from the U.S. Food and Drug Administration (FDA) for first-line treatment of Chronic Myelomonocytic Leukemia (CMML) in combination with Azacitidine, showcasing its potential in the market [3] - The company holds global intellectual property and commercialization rights for IMM01, with a patent family that includes granted patents in China, the United States, Japan, and the European Union [3]

Group 1 - Company announced the successful completion of the first patient dosing in the Phase IB/II clinical trial of IMM2510 in combination with IMM01 for the treatment of advanced solid tumors, marking a milestone in innovative cancer immunotherapy [1] - IMM2510 (Pervirafusp alpha) is a dual-specific molecule targeting Vascular Endothelial Growth Factor (VEGF) and Programmed Cell Death Ligand 1 (PD-L1), designed to inhibit angiogenesis, reduce tumor size, and enhance immune response sensitivity [1] - The mechanism of IMM2510 includes blocking the PD-L1/Programmed Cell Death Protein 1 (PD-1) interaction and inducing antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP), activating T cells, natural killer cells, and macrophages [1] Group 2 - The company entered into a licensing and collaboration agreement with Axion Bio, Inc., granting the company commercialization rights for IMM2510 in the Greater China region while allowing Axion Bio, Inc. exclusive rights for research, development, and commercialization outside this region [2] - The core product IMM01 (Tideglusib) is an innovative molecule targeting CD47, being the first SIRPα-Fc fusion protein to enter clinical stages in China, designed to activate macrophages through dual mechanisms [3] - IMM01 has received orphan drug designation from the FDA for first-line treatment of Chronic Myelomonocytic Leukemia (CMML) in combination with Azacitidine, showcasing its potential in the market [3] - The company holds global intellectual property and commercialization rights for IMM01, with a patent family that includes granted patents in China, the United States, Japan, and the European Union [3]

Core Viewpoint - The research indicates that black phosphorus nanosheets (BPP) can enhance mitochondrial oxidative phosphorylation (OXPHOS) in tumor cells, potentially improving cancer immunotherapy outcomes [2][3][5][7]. Group 1: Research Findings - The study developed PEG-modified black phosphorus nanosheets (BPP) that metabolize into phosphates within tumor cells, promoting OXPHOS and improving cancer immunotherapy effectiveness [3][5]. - BPP regulates multiple signaling pathways, inhibits the expression of pro-survival genes, and reduces PD-L1 protein levels in melanoma cells, thereby suppressing cancer progression [5]. - BPP enhances immune regulation by increasing pro-inflammatory cytokine levels in serum, elevating CD8+ T cell levels in tumors and lymph nodes, and decreasing regulatory T cell (Treg) levels [5]. Group 2: Implications for Cancer Treatment - The research suggests that BPP may serve as a dual-function drug, combining tumor chemotherapy and immune enhancement capabilities [7].

Core Viewpoint - Kangfang Biopharma's drug Iwosimab (PD-1/VEGF dual antibody) has shown significant improvement in progression-free survival (PFS) compared to Tislelizumab in a Phase III clinical trial for advanced squamous non-small cell lung cancer (sq-NSCLC) [1][2] Group 1: Clinical Trial Results - The HARMONi-6 study demonstrated that Iwosimab combined with chemotherapy significantly extends PFS, achieving a median PFS of 11.14 months compared to 6.90 months for Tislelizumab, with a hazard ratio of 0.60 (P<0.0001), resulting in an absolute difference of 4.24 months [1] - The new indication application for Iwosimab in treating sq-NSCLC based on the HARMONi-6 study results has been accepted for review by the National Medical Products Administration (NMPA) [1] Group 2: Drug Approvals and Pipeline - Iwosimab has been included in the national medical insurance drug list, with 13 Phase III clinical trials currently in progress, covering various cancers including lung cancer and cholangiocarcinoma [2] - Iwosimab has received approval for two indications in China, with the first being for EGFR-mutant locally advanced or metastatic non-squamous NSCLC after EGFR-TKI treatment, and the second for PD-L1 positive locally advanced or metastatic NSCLC [2] Group 3: Other Drug Developments - Cardunili has received approval for a new indication in first-line treatment of cervical cancer, with approximately 10 Phase III or registration clinical trials actively advancing [3] - Cardunili is pursuing around 20 indications through combination therapies, with three indications currently approved in China [3]

Core Viewpoint - Kangfang Biopharma (09926) announced that its drug Iwosimab (PD-1/VEGF dual antibody) combined with chemotherapy achieved the primary endpoint of progression-free survival (PFS) in a Phase III clinical study for advanced squamous non-small cell lung cancer (sq-NSCLC), outperforming the comparator drug Tislelizumab combined with chemotherapy [1] Group 1: Clinical Research and Results - The HARMONi-6 study demonstrated that Iwosimab combined with chemotherapy significantly extended PFS compared to Tislelizumab combined with chemotherapy, with a median PFS of 11.14 months for Iwosimab versus 6.90 months for Tislelizumab (HR=0.60, P<0.0001), resulting in an absolute difference of 4.24 months [1] - Based on the positive results from the HARMONi-6 study, the supplemental new drug application (sNDA) for Iwosimab combined with chemotherapy for sq-NSCLC was accepted by the National Medical Products Administration (NMPA) in July 2025 and is currently under review [1] Group 2: Drug Approvals and Pipeline - Iwosimab has been included in the National Medical Insurance Drug List, with 13 Phase III clinical studies ongoing, covering various cancers including lung cancer, cholangiocarcinoma, and head and neck squamous cell carcinoma [2] - Iwosimab has received approval for two indications in China, with the first being for locally advanced or metastatic non-squamous NSCLC after progression on EGFR-TKI therapy, which has been successfully included in insurance; the second indication for PD-L1 positive locally advanced or metastatic NSCLC is expected to receive NMPA approval in April 2025 [2] - The drug Kadunili has also received approval for a new indication in first-line treatment of cervical cancer, with approximately 10 Phase III or registration clinical trials actively progressing [2]