MR1

01月29日的《热心肠日报》，我们解读了 15 篇文献，关注：瘤内菌群，癌症疫苗，工程菌，大肠癌，胃癌，林奇综合征，lncRNA，诺和诺德口服GLP-1，奥林巴斯，Taewoong Medical，ZIVO Bioscience，Naronapride，南方乳业。 该篇日报由R·AI辅助创作生成，人工审核校对。 国内团队：瘤内菌群与癌症发展和治疗（综述） Signal Transduction and Targeted Therapy——[39.3] ① 武汉协和医院金阳、Wang Sufei团队对瘤内菌群的概念、发展、来源、异质性和致癌机制进行综述，探讨其在肿瘤预后中的潜在作用，并讨论了靶向瘤内菌群的抗肿瘤治疗方法及其研究前景和局限性；② 瘤内菌群具有3种可能来源：粘膜屏障、邻近组织及血源性侵袭，其结构和丰度在不同类型、亚型和阶段的癌症中显著差异；③ 瘤内菌群通过诱导基因组不稳定性和突变、影响表观遗传修饰、促炎、规避免疫破坏、调节代谢及激活侵袭和转移等途径，促进肿瘤的发生和发展；④ 通过抗生素、噬菌体、工程细菌及溶瘤病毒等方案靶向瘤内菌群，精确治疗和预防癌症；⑤ 未来，应加强探索基于微生物干预的联合治疗策略以提高临床治疗效果。 【原文信息】 Intratumoural microbiota: a new frontier in cancer development and therapy 2024-01-10 , doi: 10.1038/s41392-023-01693-0 肖波+刘尽尧：用于大肠癌治疗的口服原位纳米疫苗 ACS Nano——[17.1] ① 西南大学肖波团队联合上海交通大学刘尽尧团队成功开发了一种口服纳米药物（Ce6/R837@Lp127NPs）：基于丝蛋白并负载声敏剂Ce6和免疫佐剂R837的纳米颗粒为核心，表面涂有植物提取脂质和聚乙烯醇p127；② 该纳米药物通过胃肠道时保持稳定，并在超声辐照下具有改善的运动活性，可实现对结肠黏膜的有效浸润和特异性肿瘤穿透；③ 该纳米药物通过声动力治疗诱导CRC细胞的免疫原性死亡，并在R837存在下产生新抗原作为有效原位疫苗；④ 结合阻断免疫检查点，联合治疗可抑制原位肿瘤、根除远端肿瘤，并调节肠道菌群；⑤ 本研究成功开发首个口服原位疫苗，为针对CRC个性化疫苗开发提供了平台。 【原文信息】 An Oral Nanomedicine Elicits In Situ Vaccination Effect against Colorectal Cancer 2024-01-19 , doi: 10.1021/acsnano.3c11436 Nature子刊：新型癌症疫苗在KRAS突变肿瘤患者具有潜在治疗效果 Nature Medicine——[82.9] ① Nature Medicine近期发表一项针对胰腺癌和结直肠癌的I期临床试验结果，新型癌症疫苗ELI-002 2P安全，且诱导明显的T细胞反应，对KRAS突变的肿瘤具有潜在治疗效果；② ELI-002 2P是使用G12D和G12R突变KRAS（mKRAS）肽进行两亲性修饰，同时联合CpG佐剂，来增强淋巴结递送和免疫应答；③ 纳入20名胰腺癌和5名结直肠癌患者，84%检测出mKRAS特异性T细胞反应（59%同时存在CD4+和CD8+），21名患者（84%）出现了肿瘤生物标志物反应，6名（24%）出现生物标志物清除，中位无复发生存期为16.33个月；④ 疗效与T细胞反应的增幅相关，T反应增幅大和小的中位肿瘤生物标志物减少为-76.0%与-10.2%，中位无复发生存期分别为未达到和4.01个月；⑤ ELI-002 2P疫苗在免疫治疗难治的KRAS突变肿瘤患者中表现出潜在的治疗效果。 【原文信息】 Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial 2024-01-09 , doi: 10.1038/s41591-023-02760-3 Nature子刊：工程益生菌用于肠道肿瘤探测与治疗 Nature Communications——[16.6] ① 口服大肠杆菌Nissle 1917（EcN）可在结直肠癌（CRC）易感基因工程小鼠模型和CRC原位模型的结肠腺瘤中选择性定植；② 临床试验显示CRC患者服用EcN后肿瘤样本中EcN富集高于正常组织；③ 工程改造的EcN可产生水杨酸盐小分子，口服后导致腺瘤小鼠的尿液中水杨酸盐明显高于健康对照组；④ 口服工程改造的EcN可在肿瘤部位局部释放GM-CSF和阻断PD-L1/CTLA-4的纳米抗体，减少腺瘤负担约50%；⑤ 本研究成功开发EcN作为口服平台，通过产生筛查和治疗分子来检测疾病和治疗CRC。 【原文信息】 Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia 2024-01-20 , doi: 10.1038/s41467-024-44776-4 国内团队：口服活体细菌作为肿瘤细胞焦亡增强剂 Nano Today——[17.4] ① 细菌抗肿瘤疗法因细胞焦亡程度不足受到应用限制，沈阳药科大孙孟驰、孙进和浙大李洪军团队通过在金属还原菌株希瓦氏菌MR-1和吡喃糖氧化酶过表达大肠杆菌表面修饰透明质酸，再口服蔗糖铁，可实现细胞焦亡增强剂的效果；② 基于修饰的菌株在体外进行了细胞焦亡增强测试，结果显示细菌增强剂可激活CT1癌细胞的NLRP3/Caspase-1/GSDMD途径诱导细胞焦亡；③ 在结肠炎相关结肠癌、原位和腹膜转移结肠癌、异种移植远端转移结肠癌多种小鼠模型中验证了细菌增强剂的抑癌能力，同时发现细菌不会透过肠屏障引起败血症；④ 细菌诱导的焦亡效应促进肿瘤内部的免疫原性反应，激活胃肠组织中的T淋巴细胞成熟；⑤ MR-1通过介导三价铁向二价铁还原，大肠杆菌通过氧化葡萄糖产过氧化氢，二价铁与过氧化氢产生毒性羟基自由基激活细胞焦亡。 【原文信息】 An oral bacterial pyroptosis amplifier against malignant colon cancer 2023-12-08 , doi: 10.1016/j.nantod.2023.102091 Cell子刊：肠癌细胞对大肠杆菌毒素的耐受性，与同源重组和化疗抵抗相关 Cell Reports Medicine——[14.3] ① 不同的结肠癌（CRC）细胞系对基因毒素colibactin的耐受能力不同，基于CRISPR构建了不同DNA修复能力途径缺陷的CRC细胞，通过筛选发现DNA损伤修复-同源重组（HR）对毒素耐受贡献最大；② 在不同HR水平的CRC细胞系中观察到colibactin耐受的相关性，在HR缺陷或colibactin耐受性低的细胞系中重建HR可提高colibactin耐受能力；③ 长期感染colibactin会选择出耐受的CRC细胞系，并表现出恢复的HR活性；④ colibactin的敏感性与伊立替康活性代谢产物SN38的反应相关，细胞系或患者来源细胞中colibactin耐受细胞对SN38交叉耐药；⑤ 携带pks基因岛的CRC回顾性人群队列数据表现出对伊立替康的耐药性趋势。 【原文信息】 Tolerance to colibactin correlates with homologous recombination proficiency and resistance to irinotecan in colorectal cancer cells 2024-01-08 , doi: 10.1016/j.xcrm.2023.101376 瘤内细菌与大肠癌临床病理和分子肿瘤特征的关联研究 British JouRNAl of Cancer——[8.8] ① 纳入1697个肿瘤DNA样本，研究瘤内pks+大肠杆菌（pE）、产肠毒素脆弱拟杆菌和具核梭杆菌（Fn）及其与结直肠癌（CRC）临床病理学和分子肿瘤特征的关系；② 瘤内pE而非pks+大肠杆菌-与APC:c.835-8 A>G体细胞突变CRC相关，且在早发CRC中具有特异性；③ Fn与DNA错配修复缺陷（MMRd）、BRAF:c.1799T>A p.V600E突变、CpG岛甲基化表型、近端肿瘤位置和高水平的肿瘤浸润淋巴细胞相关；④ MMRd亚组分层分析中，Fn与Lynch综合征、MLH1甲基化和双MMR体细胞突变MMRd亚组相关。 【原文信息】 Intratumoral presence of the genotoxic gut bacteria pks+ E. coli, Enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum and their association with clinicopathological and molecular features of colorectal cancer 2024-01-10 , doi: 10.1038/s41416-023-02554-x 肠道菌群代谢产物丁酸有望成为胃癌免疫治疗的新靶点 Gut Microbes——[12.2] ① 胃癌的早期检测和手术治疗对于取得良好的预后至关重要，但四期和复发性胃癌预后不佳，因此急需新的胃癌治疗方法，该研究发现菌群代谢产物丁酸可以逆转胃癌患者的免疫抑制状态和胃癌细胞生长；② 晚期胃癌（AGC）患者外周血免疫细胞中程序性死亡配体1（PD-L1）和白细胞介素（IL）-10的水平高于健康组；③ AGC患者肠道菌群中的梭菌和双歧杆菌的丰度低于健康个体，这些菌群的代表性菌群代谢产物丁酸抑制了免疫细胞中PD-L1和IL-10的表达水平，并抑制肿瘤生长；④ 恢复肠道菌群及其代谢功能抑制了胃癌肿瘤生长，并逆转由于胃癌患者PBMCs和肿瘤细胞中PD-L1和IL-10水平增加而导致的免疫抑制表型；⑤ 这些发现为恢复肠道菌群及其代谢功能以逆转AGC患者免疫抑制状态提供了新思路，有望为胃癌的免疫治疗提供新的策略。 【原文信息】 Gut microbiome-derived butyrate inhibits the immunosuppressive factors PD-L1 and IL-10 in tumor-associated macrophages in gastric cancer 2024-01-10 , doi: 10.1080/19490976.2023.2300846 江南大学：LINC01852抑制结直肠癌的化疗耐药 Molecular Cancer——[37.3] ① 江南大学的黄朝晖团队发表文章，揭示了长链非编码RNA——LINC01852在抑制结直肠癌（CRC）恶化和化疗耐药中的重要作用，其通过调节SRSF5介导的PKM选择性剪接而抑制CRC细胞的化疗耐药，为CRC的治疗提供了新的潜在靶点和策略；② LINC01852在CRC中下调，抑制了细胞增殖和化疗耐药；③ LINC01852通过增加TRIM72介导的SRSF5泛素化和降解，抑制了SRSF5介导的PKM的选择性剪接，从而降低PKM2的产生；④ 过表达LINC01852通过抑制PKM2介导的糖酵解，诱导细胞从有氧糖酵解转向氧化磷酸化，发生代谢转变，来减轻CRC细胞的化疗耐药；⑤ 这些发现揭示了LINC01852/TRIM72/SRSF5/PKM2信号通路在CRC中的重要作用，为开发新的治疗策略提供了理论基础。 【原文信息】 LINC01852 inhibits the tumorigenesis and chemoresistance in colorectal cancer by suppressing SRSF5-mediated alternative splicing of PKM 2024-01-24 , doi: 10.1186/s12943-024-01939-7 林奇综合征结直肠癌基因组图谱揭示突变新抗原 Gastroenterology——[29.4] ① 对Lynch综合征携带者（LS）肠道息肉（PWOMPs）、前癌病变和早期癌症进行全外显子和转录组测序，分析其突变新抗原；② 83%癌症、63%晚期前癌病变和20%前癌病变中每Mb有超过10个突变；③ 平均每个癌症、晚期前癌、前癌病变样本中分别有616、294、107个MHC-I新抗原，PWOMPs中未检测到新抗原；④ 预测的前100个新抗原中，65%在体外具有免疫原性，且存在92%癌症、50%晚期前癌病变和29%前癌病变中；⑤ MMRd癌症和前癌病变中天然CD8+和记忆CD4+ T细胞水平增加；⑥ LS癌症发生初期，不稳定微卫星位点内产生共享移码新抗原且可诱导T细胞反应，为针对LS前癌病变和早期癌症的疫苗开发提供了可能性。 【原文信息】 Genomic Landscape of Lynch Syndrome Colorectal Neoplasia Identifies Shared Mutated Neoantigens for Immunoprevention 2024-01-18 , doi: 10.1053/j.gastro.2024.01.016 诺和诺德口服司美格鲁肽在华获批上市 ① 1月26日，诺和诺德口服司美格鲁肽片获国家药监局批准上市，成为国内首个口服GLP-1（胰高血糖素样肽-1）受体激动剂；② 司美格鲁肽具有多重作用，包括优异的降糖、减重效果以及明确的心血管获益功效等；③ 2019年9月，司美格鲁肽片获FDA批准治疗2型糖尿病，成为了全球首个获批的口服GLP-1药物；④ 目前，中国已有9款GLP-1受体激动剂获批上市，其中8款通过皮下注射给药，而仅有司美格鲁肽片一款为口服制剂，摆脱了注射带来的不便和心理折磨。 【原文信息】 重磅！口服司美格鲁肽在华获批上市 2024-01-26 , 医药魔方 奥林巴斯完成对Taewoong Medical收购 ① 1月24日，奥林巴斯宣布已完成对韩国医疗器械制造商Taewoong Medical公司的收购；② Taewoong Medical公司的产品组合将纳入奥林巴斯治疗解决方案部门；③ 2023年2月，奥林巴斯宣布已同意以3.7亿美元（约合人民币26.5亿元）的价格收购Taewoong Medical；④ Taewoong Medical是一家专为胆道、食道、结肠和十二指肠治疗打造创新解决方案的医疗器械制造商，致力于通过生产高质量和创新的微创医疗设备，推进医疗技术升级并改善患者的生活质量。 【原文信息】 Olympus closes the acquisition of Korean gastrointestinal stent company, Taewoong Medical Co., Ltd 2024-01-24 , HealthCareBusiness News ZIVO Bioscience替抗产品预防治疗肉鸡球虫病验证研究获积极结果 ① 1月23日，生物技术公司ZIVO Bioscience宣布，其非抗生素免疫调节产品在预防和治疗肉鸡球虫病的42天验证研究中，展现出积极疗效；② 球虫病是一种原生动物疾病，为控制该疾病，全球家禽业每年花费超过15亿美元；③ 新产品旨在增强免疫反应，使家禽能够在不使用抗生素的情况下，对抗球虫病并减少该疾病的负面影响；④ 研究结果显示，ZIVO Bioscience的产品在真实环境中的表现与市场领先的抗球虫病产品相当；⑤ ZIVO Bioscience计划与全球动物健康公司合作，以商业化该产品。 【原文信息】 ZIVO Bioscience Reports Positive Efficacy Results from 42-Day Validation Study with Non-Antibiotic Immune-Modulating Product for the Prevention and Treatment of Coccidiosis in Broiler Chickens 2024-01-23 , BioSpace Renexxion胃肠病新药Naronapride IND申报获批 ① 1月24日，生物制药公司Renexxion宣布，候选药物Naronapride治疗PPI-nrsGEED（质子泵抑制剂无反应性胃食管反流病）新药临床试验申请（IND），获得FDA批准 ；② 候选药物Naronapride是一款潜在同类最优的泛消化道动力药物，已被证明兼具血清素5HT4受体激动性和多巴胺D2受体拮抗性；③ 此前，Naronapride已获得多项2期试验阳性结果；④ 在治疗慢性特发性便秘和胃食管反流病适应证上，Naronapride已进入3期临床评价阶段。 【原文信息】 Renexxion Ireland Ltd. Announces FDA Clearance of Investigational New Drug (IND) Application for Naronapride to Treat PPI-Non-Responsive Symptomatic GERD 2024-01-24 , GlobeNewswire 南方乳业宣布更改上市辅导备案板块 ① 1月22日，在新三板挂牌不足一月之时，南方乳业宣布，将上市辅导备案板块由上海证券交易所主板变更为北京证券交易所，辅导备案证监局仍为贵州证监局，辅导机构仍为中信证券；② 南方乳业与中信证券签署了《贵州南方乳业股份有限公司与中信证券股份有限公司关于向不特定合格投资者公开发行股票并在北京证券交易所上市之辅导协议》；③ 根据已披露的《公开转让说明书》，南方乳业符合在北交所上市的财务条件。④ 但目前南方乳业为基础层挂牌公司，须进入创新层后方可申报公开发行股票并在北交所上市，存在因未能进入创新层而无法申报的风险。 【原文信息】 新三板挂牌不足一月，南方乳业又有新动作！ 2024-01-24 , FoodTalks 感谢本期日报的审核者：圆圈儿，章台柳，Johnson，MD，Richard，lxx，Alex Zhang 点击阅读过去10天的日报： 0128 | 32分综述详解：饮食如何通过菌群代谢物影响免疫？ 0127 | 今日Cell双发聚焦肠道！揭示肠道免疫和肠肝轴新机制 0126 | 改善心衰，肠菌代谢物提供治疗新思路 0125 | 高糖高油食品如何"绑架"大脑？Cell子刊揭示肠脑机制 0124 | 郝海平等Cell子刊：精神压力如何伤肠道？揭晓肠菌介导的脑-肠轴机制 0123 | 肠道致病菌如何长期感染？高分Cell子刊揭示机制 0122 | 国内团队多点开花，十文一览消化道癌症研究新进展 0121 | 补充剂能改善儿童呼吸道感染吗？大型荟萃分析探究竟 0120 | Cell重磅：论菌群的"社会性"及其对健康的影响 0119 | 今日Cell：母乳如何守护宝宝肠道？新机制揭晓

Taking a significant leap in the field of vaccine development, Schulich School of Medicine & Dentistry researchers have discovered a potential 'super molecule' that can bolster the effectiveness of several vaccines against viral diseases, including influenza, COVID-19 and smallpox. Taking a significant leap in the field of vaccine development, Western researchers have discovered a potential 'super molecule' that can bolster the effectiveness of several vaccines against viral diseases, including influenza, COVID-19 and smallpox. A team led by Western professor Mansour Haeryfar found that a vitamin B2-derived molecule called 5-OP-RU, which is produced by bacteria, can enhance the efficacy of several vaccines for viral diseases. The study revealed the molecule binds to a protein called MR1 before stimulating a population of T lymphocytes called mucosa-associated invariant T (MAIT) cells -- essentially, one of the "first responders" that come rushing to fight off infection when a virus invades the body. The findings, recently published in PLOS Pathogens, could have significant implications for strengthening the global response to current and future viral threats. "We need better vaccines to combat viruses of pandemic potential, which are among the most vicious existential threats to human populations," said Haeryfar, professor of immunology at Western's Schulich School of Medicine & Dentistry. "Our strategy of targeting the MR1-MAIT cell axis using 5-OP-RU shows promise in generating strong antiviral immune responses in the body. This strategy could help develop more effective viral vaccines." For the study, the team of researchers used a combination of clinically relevant mouse models, human cell cultures and multiple vaccine platforms against various influenza, SARS-CoV-2 and smallpox. They found that 5-OP-RU worked in tandem with antiviral vaccines to expand MAIT cells and reprogram them to become more powerful antiviral entities. "MAIT cells are often found in the bloodstream and in mucosal tissues, including in our respiratory system, which is often the first place in which many viruses are encountered" said Haeryfar. When viruses like flu or SARS-CoV-2 get into our lungs, MAIT cells are already there and ready to fight. They respond quickly to infections, coordinate our immune response, and help destroy virus-infected cells. This makes them very attractive targets in vaccine design strategies." As for the next steps, Haeryfar and his team plan to extend their studies to test the efficacy of 5-OP-RU in several COVID vaccine candidates, including a promising Western-developed COVID-19 vaccine candidate and inhaled vaccines. "While mRNA vaccines were and remain potent in reducing the risk of severe morbidity and mortality due to COVID-19, we need more effective vaccines to prevent infection with SARS-CoV-2 variants of concern. We are now looking to investigate the possibility of using 5-OP-RU and potentially other MR1-binding molecules in inhaled vaccines," he added. The study also suggests that the unique characteristics of MAIT cells -- quick-acting entities with antibacterial and tissue repair properties -- could also help resolve secondary bacterial infections and tissue damage in the aftermath of viral infection. "It is also noteworthy that MAIT cells are evolutionarily conserved. Therefore, the results of preclinical studies are likely to be translatable to the clinic," said Haeryfar. "Everyone has the exact same MR1 protein. Therefore, immunization strategies that target MR1 and MAIT cells should work across diverse human populations, regardless of their genetic makeup." Supervised by Haeryfar, the study was spearheaded by Western graduate student Rasheduzzaman Rashu and a team of current and former Haeryfar Lab trainees including Marina Ninkov, Christine Wardell, Jenna Benoit, Nicole Wang and Courtney Meilleur. The research included contributions from Western professors David Hess, Stephen Barr, Ryan Troyer and Chil-Yong Kang, and researchers from McMaster University. This research was supported by a Canadian Institute of Health Research (CIHR) Project Grant awarded to Haeryfar.

--The molecules open the door for development of immunotherapies that are truly universal and work across HLA types, regardless of patient ancestry— PHILADELPHIA, June 13, 2023 /PRNewswire/ -- Class I major histocompatibility complex (MHC-I) proteins play an essential role in the immune system of all jawed vertebrates. The MHC-I displays peptide fragments of proteins from within the cell on the cell surface, "presenting" them to the immune system, which is constantly scanning the body for foreign or toxic antigens. When foreign peptides are identified, they trigger a cascade that allows cytotoxic T cells to eliminate intruders. This process has been exploited in the development of both vaccines and immunotherapy, wherein researchers identify fragments of peptides unique to viruses or cancer and then screen for T cells that recognize those targets and initiate an immune response. However, the current process of using MHC-I molecules as probes in vaccine and immunotherapy development is laborious. MHC-I molecules are extremely unstable, and making just one of these molecules can take a week, making it prohibitive to scan large libraries of peptides in an efficient manner. Now, researchers from Children's Hospital of Philadelphia (CHOP) have potentially solved this problem by engineering stable, universal MHC-I molecules that can be produced rapidly at scale, allowing researchers not only to develop vaccines and immunotherapies more quickly but also to identify molecules that can work broadly across the population. The findings were published today in the Proceedings of the National Academy of Sciences. "The findings in this paper have the potential to revolutionize this field, both in the way we manufacture these molecules and the rate at which we can screen for effective and universal immunotherapies," said senior author Nikolaos G. Sgourakis, PhD, Associate Professor in the Center for Computational and Genomic Medicine at Children's Hospital of Philadelphia. "We are no longer limited by the instability of these molecules and the long timeframe it used to take to manufacture them. These stabilized MHC-I molecules could speed up the screening process and the subsequent development of effective therapies." Led by Sgourakis Lab members Yi Sun, Michael C. Young, and Claire H. Woodward, the researchers stabilized MHC-I molecules by focusing on their 3D structure. Classical MHC-I molecules are comprised of three major parts: a peptide antigen consisting of 8 to 15 amino acids; a light chain that is the same for all MHC-I molecules; and a highly polymorphic heavy chain. In humans, the MHC-I is called human leukocyte antigen, or HLA, which has expanded because of constant evolutionary adaptation in the human population to include more than 35,000 variants, with a variety of different residues located on groove where peptides can bind. Because HLA is so polymorphic, different HLA types display different peptide repertoires, bind different molecular chaperones, and display different T cell receptors (TCRs), which ultimately define immune responses and disease susceptibility. Thus, finding universal targets and immunotherapies that work across the human population has been challenging. To stabilize MHC-I and make it useful for universal peptide loading and screening, the researchers focused on the light chain of the molecule, since it is conserved across HLA types. The light chain performs an important role in stabilizing MHC-I molecules. As soon as the light chain falls off, it triggers the MHC-I molecule to disassemble, at which point it is essentially sent for recycling for future peptide loading, serving as a sort of "on/off" switch for the MHC-I molecule. To exploit this fundamental engineering, the researchers tethered the heavy chain to the light chain, stabilizing the MHC-I in a conformation that is "open" and receptive to peptides. The researchers confirmed the stability of these engineered MHC-I molecules through biophysical characterization, using nuclear magnetic resonance (NMR), showing that their open MHC-I molecules have enhanced stability when loaded with peptides, even those of low to moderate affinity. The researchers also demonstrated that their engineered MHC-I molecules promote peptide exchange across multiple HLA allotypes, covering representatives from five HLA-A, six HLA-B supertypes, and HLA-Ib molecules, which have many different forms. A key component of using this system to enable a high-throughput peptide exchange platform was the design of customized "placeholder" peptides containing unnatural amino acid modifications, which was done in close collaboration with the lab of chemical biologist George Burslem, PhD, at the University of Pennsylvania. "The open MHC-I platform leverages minimal protein modifications to enhance ligand exchange reactions across all known HLA allotypes, as well as oligomorphic MR1 molecules which present aberrant metabolites that are associated with many tumors," Dr. Sgourakis said. "These new molecules could be a versatile tool for screening antigenic epitopes, enabling the detection of low-frequency receptors and engineered antibodies for the development of targeted therapies." This work was supported through grants by NIAID (5R01AI143997), NIDDK (5U01DK112217), and NIGMS (5R35GM125034 and R35GM142505). Additional support was provided through a Fox Chase Cancer Center pilot project grant and NIH grants P30CA006927 and T32GM132039. Sun Y, Young MC, Woodward CH, Danon JN, Truong HV, Gupta S, Winters TJ, Font-Burgada J, Burslem GM, and Sgourakis NG. "Universal open MHC-I molecules for rapid peptide loading and enhanced complex stability across HLA allotypes," Proceedings of the National Academy of Sciences, online June 13, 2023, DOI: 10.1073/pnas.2304055120. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the 595-bed hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as a new inpatient hospital with a dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Dana Bate Children's Hospital of Philadelphia (267) 426-6055 [email protected] SOURCE Children's Hospital of Philadelphia