【第47期】前沿靶點(diǎn)速遞：每周醫(yī)學(xué)研究精選
日期：2025-07-15 16:00:36
01.靶點(diǎn) IL13Rα1
應(yīng)用：治療腸道炎癥和蠕蟲(chóng)感染
來(lái)源：Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven hostdefense.Science,2025 May 22
圖源：10.1126/science.adn9850[1]
2025年6月21日，哈佛醫(yī)學(xué)院團(tuán)隊(duì)在《Science》發(fā)表研究，解析了腸道神經(jīng)元感知炎癥信號(hào)并調(diào)控免疫反應(yīng)的機(jī)制。研究發(fā)現(xiàn)，腸道內(nèi)的初級(jí)感覺(jué)神經(jīng)元（PSN）能通過(guò)IL-13Rα1受體感知IL-4和IL-13細(xì)胞因子，進(jìn)而釋放神經(jīng)肽U（NMU）和CGRPβ。這些神經(jīng)肽可增強(qiáng)腸道免疫反應(yīng)，抵御腸道蠕蟲(chóng)感染。利用基因敲除小鼠模型，研究證實(shí)了PSN在抗感染免疫中的關(guān)鍵作用，并揭示了其通過(guò)調(diào)節(jié)ILC2s細(xì)胞和巨噬細(xì)胞功能影響免疫防御的機(jī)制。這一發(fā)現(xiàn)為治療腸道炎癥和蠕蟲(chóng)感染提供了新思路。02.靶點(diǎn) CREM
應(yīng)用：CAR-NK細(xì)胞療法研究
來(lái)源：CREM is a regulatory checkpoint of CAR and IL-15 signalling in NK cells.Nature,2025 Jun 04
圖源：10.1038/s41586-025-09087-8[2]
這篇文章講的是免疫療法的新突破。研究人員發(fā)現(xiàn)，在CAR-NK細(xì)胞療法中，NK細(xì)胞里的CREM是個(gè)關(guān)鍵調(diào)控因子。他們通過(guò)一系列實(shí)驗(yàn)，比如基因工程改造NK細(xì)胞、用多種技術(shù)分析，發(fā)現(xiàn)CREM的表達(dá)受CAR激活和IL-15信號(hào)誘導(dǎo)，且與NK細(xì)胞的激活等功能相關(guān)。敲除CREM能增強(qiáng)CAR-NK細(xì)胞的抗腫瘤能力，為這種療法的發(fā)展帶來(lái)新希望。
03.靶點(diǎn) PVR/CD155
應(yīng)用：血液瘤和實(shí)體瘤治療
來(lái)源：Pan-cancer analysis identifies CD155 as a promising target for CAR-T cell therapy.Genome Med,2025 Jun 02
圖源：10.1186/s13073-025-01490-0[3]
華東師范大學(xué)杜冰團(tuán)隊(duì)發(fā)現(xiàn)，CD155在多種癌癥組織中高表達(dá)，且與癌癥患者不良預(yù)后相關(guān)，其通過(guò)抑制T細(xì)胞釋放細(xì)胞毒性因子介導(dǎo)腫瘤免疫逃逸。該團(tuán)隊(duì)構(gòu)建的靶向CD155的CAR-T細(xì)胞在體內(nèi)外多種血液瘤和實(shí)體瘤中展現(xiàn)出顯著抗腫瘤活性，且在動(dòng)物模型中未見(jiàn)明顯副作用，表明CD155有望成為CAR-T療法的理想靶點(diǎn)。
04.靶點(diǎn) R9AP
應(yīng)用：抗EBV疫苗的研究
來(lái)源：R9AP is a common receptor for EBV infection in epithelial cells and B cells.Nature,2025 Jun 18
圖源：10.1038/s41586-025-09166-w[4]
中山大學(xué)曾木圣、鐘茜團(tuán)隊(duì)在《Nature》發(fā)文，發(fā)現(xiàn)R9AP是EB病毒（EBV）感染上皮細(xì)胞和B淋巴細(xì)胞的通用受體。EBV與多種疾病相關(guān)，但此前對(duì)上皮細(xì)胞感染研究較少。該團(tuán)隊(duì)通過(guò)構(gòu)建高效感染模型，篩選發(fā)現(xiàn)R9AP在兩種細(xì)胞中均表達(dá)且對(duì)EBV感染至關(guān)重要。R9AP與EBV糖蛋白gH/gL結(jié)合，沉默或敲除R9AP可顯著抑制感染。這一發(fā)現(xiàn)顛覆了EBV利用不同受體感染兩類細(xì)胞的傳統(tǒng)認(rèn)知，為抗EBV疫苗研發(fā)提供了新靶標(biāo)。
05.靶點(diǎn) TNFR2
應(yīng)用：結(jié)直腸癌免疫治療
來(lái)源：Dual blockade of TNFR2 and CD47 reshape tumor immune microenvironment and improve antitumor effects in colorectal cancer.Mol Ther,2025 May 30
圖源：10.1016/j.ymthe.2025.05.032[5]
南京大學(xué)魏繼武團(tuán)隊(duì)在《Molecular Therapy》發(fā)表研究，提出一種針對(duì)結(jié)直腸癌的新型免疫治療策略。該策略通過(guò)構(gòu)建雙特異性融合抗體ATA47，同時(shí)阻斷CD47與TNFR2信號(hào)通路，并利用溶瘤腺病毒載體實(shí)現(xiàn)腫瘤原位遞送。此方法有效重塑腫瘤免疫微環(huán)境，增強(qiáng)抗腫瘤免疫，克服了傳統(tǒng)CD47阻斷療法的療效限制和副作用問(wèn)題，為結(jié)直腸癌免疫治療提供了新路徑。
06.靶點(diǎn) STING
應(yīng)用：腸道疾病的治療
來(lái)源：ILC3s sense gut microbiota through STING to initiate immune tolerance.Immunity,2025 Jul 08
圖源：10.1016/j.immuni.2025.05.016[6]
康奈爾大學(xué)團(tuán)隊(duì)在《Immunity》發(fā)表研究，發(fā)現(xiàn)III型天然淋巴細(xì)胞（ILC3s）通過(guò)STING感知腸道菌群，促進(jìn)免疫耐受并維持腸道穩(wěn)態(tài)。研究揭示了ILC3s中STING的適度激活可啟動(dòng)免疫耐受，而過(guò)度激活則會(huì)導(dǎo)致ILC3死亡，與炎癥性腸病（IBD）相關(guān)。這一發(fā)現(xiàn)為腸道疾病的治療提供了新思路。07.靶點(diǎn) SELPLG/PSGL1
應(yīng)用：血癌免疫研究
來(lái)源：Cisplatin and temozolomide combinatorial treatment triggers hypermutability and immune surveillance in experimental cancer models.Cancer Cell,2025 Jun 10
圖源：10.1016/j.ccell.2025.05.014[7]
多篇新研究帶來(lái)醫(yī)學(xué)突破：Cancer Cell研究發(fā)現(xiàn)順鉑和替莫唑胺聯(lián)用可提升結(jié)直腸癌和乳腺癌免疫治療效果；Science Immunology研究揭示PSGL-1在血癌免疫逃逸中的關(guān)鍵作用，開(kāi)發(fā)出人源化PSGL-1抗體；Neuron研究發(fā)現(xiàn)ZBTB7A是抑郁癥相關(guān)改變的關(guān)鍵分子；Cell Stem Cell研究顯示PGE2可逆轉(zhuǎn)肌肉干細(xì)胞功能障礙；Nature Neuroscience研究解析了阿爾茨海默病中髓鞘-軸突異常的機(jī)制。08.靶點(diǎn) UBE2F、ARIH2
應(yīng)用：抗腫瘤免疫治療
來(lái)源：Enhancing anti-tumor immunity of natural killer cells through targeting IL-15R signaling.Cancer Cell,2025 Jun 10
圖源：10.1016/j.ccell.2025.05.011[8]
莫納什大學(xué)團(tuán)隊(duì)在《Cancer Cell》發(fā)表研究，通過(guò)CRISPR篩選發(fā)現(xiàn)泛素依賴的IL-15R降解是IL-15R信號(hào)傳導(dǎo)的主要調(diào)控因素。關(guān)鍵靶點(diǎn)包括UBE2F、ARIH2等，敲除這些基因可增強(qiáng)NK細(xì)胞的抗腫瘤活性。研究揭示了UBE2F和ARIH2作為潛在的免疫治療藥物靶點(diǎn)，為增強(qiáng)NK細(xì)胞的抗腫瘤免疫提供了新策略。產(chǎn)品推薦
| 靶點(diǎn) | 重組蛋白 | 貨號(hào) |
| ARIH2 | Recombinant Human E3 ubiquitin-protein ligase ARIH2 (ARIH2) | CSB-MP002069HU |
| PVR | Recombinant Human Poliovirus receptor (PVR) (I340M), partial (Active) | CSB-MP019093HU(M) |
| CREM | Recombinant Mouse cAMP-responsive element modulator (Crem) | CSB-MP005961MO |
| IL13RA1 | Recombinant Human Interleukin-13 receptor subunit alpha-1 (IL13RA1) | CSB-CF011591HU |
| SELPLG | Recombinant Human P-selectin glycoprotein ligand 1 (SELPLG), partial | CSB-MP621767HU |
| RGS9BP | Recombinant Human Regulator of G-protein signaling 9-binding protein (RGS9BP), partial | CSB-MP765076HU |
| STING1 | Recombinant Human Stimulator of interferon genes protein (STING1), partial | CSB-YP023754HU1c7 |
| TNFRSF1B | Recombinant Human Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B), partial (Active) | CSB-MP023978HU2 |
| UBE2F | Recombinant Human NEDD8-conjugating enzyme UBE2F (UBE2F) | CSB-EP850248HU |
參考文獻(xiàn)
[1] Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven hostdefense.Science,2025 May 22
[2]CREM is a regulatory checkpoint of CAR and IL-15 signalling in NK cells.Nature,2025 Jun 04
[3]Pan-cancer analysis identifies CD155 as a promising target for CAR-T cell therapy.Genome Med,2025 Jun 02
[4]R9AP is a common receptor for EBV infection in epithelial cells and B cells.Nature,2025 Jun 18
[5]Dual blockade of TNFR2 and CD47 reshape tumor immune microenvironment and improve antitumor effects in colorectal cancer.Mol Ther,2025 May 30
[6]ILC3s sense gut microbiota through STING to initiate immune tolerance.Immunity,2025 Jul 08
[7]Cisplatin and temozolomide combinatorial treatment triggers hypermutability and immune surveillance in experimental cancer models.Cancer Cell,2025 Jun 10
[8]Enhancing anti-tumor immunity of natural killer cells through targeting IL-15R signaling.Cancer Cell,2025 Jun 10
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