Sulfur Hexafluoride Lipid-Type A Microspheres

▎药明康德内容团队报道2024年美国临床肿瘤学会（ASCO）年会已于今日（当地时间5月31日）在美国芝加哥正式开幕。根据ASCO官网摘要信息，今年共有5800+项研究入选本届大会，其中有426项研究入选了“口头报告环节（Oral Abstract Session）”和“快速口头报告（Rapid Oral Abstract Session）环节”。梳理这些口头报告研究，我们发现有近20项细胞疗法相关研究入选，包括了CAR-T细胞疗法、TCR-T细胞疗法、TIL疗法、基于细胞的现货型免疫疗法等等。在这其中，多家中国公司的细胞疗法也入选了ASCO大会口头报告，如科济药业Claudin18.2靶向CAR-T、艺妙神州靶向GUCY2C的CAR-T、博生吉CD7靶向CAR-T产品等。我们注意到，入选本次ASCO大会口头报告的细胞疗法中，有至少6项研究针对的适应症为实体瘤，涵盖胃肠道肿瘤、滑膜肉瘤、肝癌、乳腺癌、黑色素瘤等。在细胞治疗领域，实体瘤曾经是一座难以逾越的高峰，而近年来越来越多的新疗法、新技术正在解决这一挑战，并取得临床突破。本文中我们将一起看看针对实体瘤适应症的细胞疗法，看看它们的临床表现如何？注：本表由《医药观澜》根据ASCO官网摘要整理，如有遗漏，欢迎补充。西比曼生物/阿斯利康：C-CAR031作用机制：自体抗GPC3 CAR-T疗法适应症：肝细胞癌C-CAR031是一种针对肝细胞癌的自体抗GPC3的CAR-T疗法。本次入选口头报告的是该产品治疗晚期肝细胞癌（HCC）患者的1期研究结果。GPC3是HCC中过表达的表面抗原，在健康组织中几乎不存在。截至2024年1月5日，共有24例患者接受了4个剂量水平（DLs）的C-CAR031输注。所有患者均可进行安全性评估。未观察到剂量限制性毒性和免疫效应细胞相关神经毒性综合征（ICANS）。22个患者可评估疗效。90.9%的患者肿瘤缩小，肝内病变和肝外病变患者的中位肿瘤缩小率为44.0%（范围为3.4%~94.4%）。所有患者疾病控制率（DCR）为90.9%，客观缓解率（ORR）为50.0%，DL4的ORR为57.1%。该研究显示C-CAR031在接受过重度治疗的晚期HCC患者中具有可控的安全性和增强的抗肿瘤活性。艺妙神州：IM96作用机制：靶向GUCY2C的CAR-T疗法适应症：结直肠癌IM96是一款靶向鸟苷酸环化酶2C（GUCY2C）的CAR-T疗法，本次入选口头报告的是该产品治疗转移性结直肠癌患者的1期研究结果。GUCY2C在结直肠癌的所有阶段均异位表达。截至2023年12月，20名患者入组并注射了IM96，所有患者随访时间为7~19个月。安全性数据显示，只有5%的患者表现出神经毒性和3级细胞因子释放综合征（CRS），研究没有达到剂量限制毒性和最大耐受剂量。19例可评估患者中，DCR为73.7%，ORR为26.3%。DL3组（12×108）患者的ORR为40.0%，与肝转移与否无关。DL3组中位无进展生存期为7个月，中位缓解持续时间为10个月。在所有患者中，肿瘤应答与癌胚抗原水平的显著降低相关。本研究表明，IM96在错配修复完整（pMMR）mCRC患者中具有持久的疗效和可接受的安全性，特别是在肝转移患者中显示出较高的治疗潜力。科济药业：CT041作用机制：靶向Claudin18.2自体CAR-T细胞候选产品适应症：胃肠道肿瘤CT041是一种靶向Claudin18.2蛋白的自体CAR-T细胞候选产品，正在针对晚期胃癌/食管胃结合部腺癌的确证性2期临床试验。本次入选口头报告的是一项治疗胃肠道肿瘤患者的1期临床研究数据。疗效数据显示，所有患者的ORR和DCR分别达到37.8%和75.5%。所有患者的中位无进展生存期（PFS）和中位总生存期（OS）分别为4.4个月和8.4个月。在接受CT041单药治疗的可评估疗效的胃癌患者中，有可测量疾病（n=47）的ORR和DCR分别达到57.4%和83.0%，所有可评估疗效的胃癌患者（n=55）的中位PFS和中位OS分别为5.8个月和9.7个月。研究人员认为，CT041在大量预处理的Claudin18.2阳性晚期GI癌症患者中显示出有希望的安全性和高度令人鼓舞的疗效。Adaptimmune：letetresgene autoleucel（lete-cel）作用机制：靶向NY-ESO-1抗原的TCR-T疗法适应症：滑膜肉瘤或粘液样/圆形细胞脂肪肉瘤Lete-cel为一种靶向NY-ESO-1实体瘤抗原的工程化T细胞受体（TCR）-T细胞疗法。NY-ESO-1通过在HLA-A*02于滑膜肉瘤和黏液样/圆细胞脂肪肉瘤（MRCLS）中高度表达。本次入选口头报告的是一项2期临床研究结果。研究纳入98名滑膜肉瘤和MRCLS患者，45名患者可评估疗效。结果显示，总体ORR为40%（包括2例CR，16例PR），其中滑膜肉瘤和MRCLS患者的ORR分别为39%和41%。中位反应持续时间为10.6个月。在该研究中，不良事件与先前观察到的一致。研究人员认为，该研究进一步支持了Lete-cel作为晚期滑膜肉瘤和MRCLS疗法的潜力。Obsidian Therapeutics：OBX-115作用机制：靶向IL-15的TIL疗法适应症：黑色素瘤OBX-115是一款保留白细胞介素2（IL2）的工程化肿瘤浸润淋巴细胞（TIL）疗法，该产品使用经FDA批准的小分子药物乙酰唑胺（ACZ）调节膜结合IL15的表达，为TIL的扩增和存续提供细胞因子支持，因此患者在接受该疗法治疗时不需要同时接受高剂量IL2。该产品目前正处于1/2期多中心研究阶段。入选口头报告的是一项1期研究结果，评估了OBX-115方案在ICI耐药、不可切除/转移性黑色素瘤患者中的疗效和安全性。截至2024年1月2日，9名黑色素瘤患者接受了OBX-115输注，他们既往治疗的中位线为3。在至少12周随访的患者中（n=6），按RECIST v1.1计算的ORR为50%（2例CR，1例PR，3例SD）；所有反应都发生在第6~18周之间，最长反应持续时间>12个月。研究人员认为，OBX-115治疗耐受性良好，产生持续加深和持久的反应，表明其可能介导无大剂量IL2的ICI耐药转移性黑色素瘤的完全缓解和持久的临床益处。BriaCell公司：Bria-IMT（SV-BR-1-GM）作用机制：基于细胞的靶向免疫疗法适应症：乳腺癌Bria-IMT方案是一种基于异体全细胞免疫疗法，可刺激患者的免疫系统诱导靶向杀死癌细胞。根据ASCO官网介绍，经皮内照射Bria-IMT的乳腺癌细胞会分泌GM-CSF，并在HLA-I和II分子上呈递肿瘤相关抗原（TAAs），直接刺激抗肿瘤免疫。PD-1免疫检查点抑制剂（CPI）进一步刺激T细胞并与SV-BR-1-GM协同作用。入选口头报告的是评估该产品结合CPI，治疗既往经过多次治疗（包括ADC和CPI治疗失败）的晚期/转移性乳腺癌的疗效和安全性。共有54例患者接受治疗，结果显示Bria-IMT方案耐受性良好，仅9%因AE退出。在接受SV-BR-1-GM III期制剂治疗的患者中（n=23，结果可评估），ORR为13%，DCR为61%，中位PFS和OS分别为4.1个月和13.3个月。研究结果显示，BRIA-IMT已显示出良好的安全性，同时为重度治疗的晚期/转移性乳腺癌患者提供益处。这项2期研究也为正在进行的3期临床研究提供了依据。值得一提的是，今年1月，BriaCell公司宣布Bria-IMT在伴有中枢神经系统（CNS）转移的晚期乳腺癌患者中达成71%的颅内客观缓解率（iORR）。目前该疗法的的关键3期试验正在进行中。除了上述产品，还有一些其它的细胞疗法入选了本届ASCO大会口头报告，用于治疗不同类型的血液肿瘤（见下表），限于篇幅，此处不再一一介绍。如欲获取本届ASCO大会口头报告的细胞疗法管线和临床试验数据，请扫描下方二维码下载表格查看。相关阅读：2024年ASCO口头报告ADC研发管线一览参考资料：[1]ASCO大会官网. From https://conferences.asco.org/am/abstracts[2]各公司公开资料及官方新闻稿本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

Scientists have discovered a highly effective, nontoxic, and less expensive way to lure hungry termites to their doom. UC Riverside scientists have discovered a highly effective, nontoxic, and less expensive way to lure hungry termites to their doom. The method, detailed in the Journal of Economic Entomology, uses a pleasant-smelling chemical released by forest trees called pinene that reminds western drywood termites of their food. They follow the scent to a spot of insecticide injected into wood. "We saw significant differences in the death rates using insecticide alone versus the insecticide plus pinene," said UCR entomologist Dong-Hwan Choe, who led the discovery. "Without pinene, we got about 70% mortality. When we added it in, it was over 95%. Native to North America, western drywood termites are environmentally important. They are drawn to dead wood above ground, and consume it with the help of microorganisms in their guts. "They are recyclers," Choe said. "And they're very common." Unfortunately for humans, the insects are unable to distinguish between dead trees and the wood used to build homes. Of particular concern in California and Florida, as well as parts of Canada and Mexico, no dwelling is immune to them. "It's only a matter of time before termites attack a house, especially in warmer parts of the states," Choe said. Fumigation is one of the most common drywood termite control techniques. Homes are covered with tents and then bombed with gas that kills the insects. In the U.S., California uses this method more than any other state. The pest control industry is under pressure to find new methods because the chemical, sulfuryl fluoride, is both a greenhouse gas and is also toxic to humans. Additionally, fumigation is an expensive process that does not provide lasting protection against termites. "Even though it is very thorough, a home can be infested again soon after fumigation is completed," Choe said. "Some people fumigate every three to five years because it doesn't protect structures from future infestations." Localized injection is an alternative strategy to control drywood termites that does not involve gas. Technicians drill holes into the infested wood to reach the termite "gallery" or lair, then inject poison into the hole to inundate the bugs. "This is a more localized treatment, and in theory, it is a better strategy when you want to control drywood termites with fewer chemicals. It's less expensive, and the treated wood may also stay protected from future infestations," Choe said. The challenge with localized injection is figuring out exactly where the bugs are hiding. Typically, this method uses a contact-based insecticide, meaning the insects must touch the poison for it to work. Using an attractant like pinene eliminates the need to hunt for the termites. "Even at low concentrations, pinene is good at attracting termites from a distance," Choe said. "We don't think it's functioning as a pheromone," Choe said. "We think the scent is more associated with their food. Smells nice… dinner time! That's the concept that we had in mind." The insecticide they used, fipronil, is also used to control ant infestations. It can be toxic to aquatic insects and pollinators if it gets into the environment. In this case it is injected into the wood, so chances of off-target effects are low. Choe's laboratory generally studies the chemical communication systems of urban insect pests to develop strategies like this one for western drywood termites. "Our study shows that if you understand insect behavior better, it's interesting by itself," Choe said. "Then there are also important implications for more effective pest management, so we can use fewer chemicals without compromising efficiency."