介绍
癌症仍然是全球最紧迫的健康挑战之一，标准治疗如手术、放疗和化疗往往未能完全根除肿瘤细胞。免疫治疗的进步突出了免疫系统在识别和摧毁癌细胞中的关键作用。然而，肿瘤微环境（TMEs）创造了诸如缺氧、酸性和免疫逃逸机制等障碍，阻碍了治疗效果。VHH抗体作为癌症免疫治疗中的一个有前途的工具正在出现。它们的小规格、高稳定性和特异性使它们能够有效地靶向肿瘤并激活免疫反应，为创新的细胞介导的癌症疗法铺平了道路。
VH抗体特征
小规格：能够穿透致密组织并跨越如血脑屏障等障碍。
高稳定性：在极端条件下保持功能，包括高温、酸性环境和放疗。
卓越的特异性和亲和力：精确靶向传统抗体无法接近的隐藏表位。
低免疫原性：减少免疫反应和非靶向效应，促进治疗安全性。
多功能工程：易于与药物、同位素或纳米颗粒结合；支持体内或体外系统的大规模生产。
改善的溶解性：增强非侵入性治疗的生物利用度和安全性。
常规单抗和重链抗体
细胞介导的免疫治疗应用
BsAb药物旨在以不同方式发挥作用。策略包括：
1. 阻断抑制性受体
VHH抗体提供了一种针对性方法来对抗肿瘤或T细胞上的抑制性受体，如PD-L1和CTLA-4。它们有效的组织穿透和精确结合恢复免疫功能并防止肿瘤逃逸。
——示例——
几项研究表明，靶向PD-L1、CXCR4和CD47的VH抗体可以有效地阻断肿瘤细胞上的这些受体并增强对癌症的免疫反应。
2. 桥接肿瘤和免疫细胞
VH抗体提供了一种新颖的方法来桥接肿瘤和免疫细胞，通过克服癌细胞使用的免疫逃逸机制，如抑制免疫反应和下调MHC分子。这些多功能剂可以靶向T细胞和自然杀伤（NK）细胞，增强它们对肿瘤的活性，同时最小化与传统单克隆抗体相关的副作用。
——示例——
基于HER2/CD3的VH抗体的双特异性酶（BiTEs）增强T细胞激活和肿瘤杀伤。
基于HER2/CD16VH抗体的双特异性酶（BiKEs）增强NK细胞反应，帮助肿瘤根除。
3.使用VH抗体结合CAR免疫细胞靶向肿瘤细胞
嵌合抗原受体（CAR）疗法，包括CAR-T和CAR-NK细胞，结合了基因工程与过继细胞疗法，并已在治疗血液癌症中显示出成功。传统上，抗原靶向域来源于单克隆抗体（mAbs）的单链片段（scFv）。最近，VH抗体因其一些优势如小尺寸、稳定性、高特异性和易于开发而成为替代品。研究表明，VH抗体结合的CAR免疫细胞在临床前和临床研究中的表现与scFv基CAR-T细胞相当。
不同类型的基于VH抗体的CAR-T细胞
单特异性CAR-T细胞：这些CAR-T细胞设计为靶向癌细胞上的单一肿瘤相关抗原（TAA）。
双特异性CAR-T细胞：这些CAR-T细胞识别同一抗原上的两个不同表位。这种设计增强了结合强度（亲和力）并减少了抗原逃逸的可能性。
寡克隆CAR-T细胞：寡克隆CAR-T细胞由混合的CAR-T细胞群组成，每个细胞靶向不同的抗原。这种方法通过同时靶向多个TAAs解决了肿瘤异质性问题，降低了抗原丢失变异的风险。
双特异性和三特异性CAR-T细胞：这些CAR-T细胞被设计为识别两个或三个不同的TAAs。通过同时靶向多个抗原，它们增强了特异性并减轻了由于抗原丢失导致的肿瘤逃逸。
通用CAR-T细胞：通用CAR-T细胞被设计为广泛适用性和灵活性。它们通常使用模块化系统，如通用受体结合适配分子，可以重新编程以靶向不同的抗原。
——示例——
功能类型 | 目标 | CAR结构 | 肿瘤类型 | 参考 |
单特异性 | BCMA | BCMA.Nb-CD8a-CD8aTM-4-1BB-CD3ζ | Hematologic malignancies | Han L, et al., (2020) |
双表位 | BCMA | BCMA.Nb-BCMA.Nb-CD8a-CD8aTM-4-1BB-CD3ζ | Hematologic malignancies | Zhao W-H, |
寡克隆 | HER2 | HER2.Nb-IgG3-Fc&Hinge-CD28-CD28-CD3ζ | Solid tumor | Jamnani FR, |
双特异性 | CD20&HER2 | CD20.Nb-IgG1-Fc-CD28TM-CD28-CD3ζ | Solid tumor | De Munter S, |
双特异性和 分裂 | CD13&TIM3 | Nb-IgG4mutant (IgG4m) hinge- CD8TM- 4-1BB, and | Hematologic malignancies | He X, et al., |
三特异性 | CD33 & CD123 & CLL1 | TanCAR-a hinge spacer-CD8TM-41BBz–CD3ζ | Hematologic malignancies | Hazelton W., (2020) |
通用 | EGFR | anti-E5B9-CD28- CD28 TM-CD28-CD3ζ | Solid tumor | Albert S, et al., (2017) |
NanoAb? 产品
NanoAb? 服务
VHH 双特异性抗体服务
VHH nanoBiTE? 服务
nanoCAR-T mRNA 服务
货号 | 产品名称 |
ABN-NAB00001 | VHH NanoAb Targeting GFP (Alexa Fluor 647) |
ABN-NAB00002 | VHH NanoAb Targeting GFP (iFluor 488) |
ABN-NAB00003 | VHH NanoAb Targeting GFP (Alexa Fluor 488) |
ABN-NAB00004 | VHH-His tag NanoAb Targeting Human CD274 |
ABN-NAB00005 | VHH NanoAb Targeting Human CD274 (iFluor 568) |
ABN-NAB00006 | VHH NanoAb Targeting Human CD274 (Alexa Fluor 488) |
ABN-NAB00007 | VHH NanoAb Targeting Human CD274 (Alexa Fluor 568) |
ABN-NAB00008 | VHH-His tag NanoAb Targeting Human TNFRSF1A |
ABN-NAB00009 | VHH-His tag NanoAb Targeting SARS-CoV-2 spike RBD |
ABN-NAB00010 | VHH-His tag NanoAb Targeting Human GFAP |
ABN-NAB00011 | VHH-His tag NanoAb Targeting mCherry |
ABN-NAB00012 | VHH-His tag NanoAb Targeting Human Vimentin |
ABN-NAB00013 | VHH-His tag NanoAb Targeting Human P53 |
ABN-NAB00014 | VHH-His tag NanoAb Targeting Human Ubiquitin, clone UB19 |
ABN-NAB00015 | VHH-His tag NanoAb Targeting Human GABAA, clone N60 |
ABN-NAB00016 | VHH-His tag NanoAb Targeting Human Tau, clone Y08 |
ABN-NAB00017 | VHH-His tag NanoAb Targeting Human Amyloid-beta, clone C40 |
ABN-NAB00018 | VHH NanoAb Targeting Human VGLUT, clone GLU23 (iFluor 488) |
ABN-NAB00019-M01J | VHH-His tag NanoAb Targeting Mouse 4-1BB, clone 2021 |
ABN-NAB00019-MF01J | VHH-His tag NanoAb Targeting Mouse 4-1BB, clone 2021 (FITC) |
ABN-NAB00020-M01J | VHH-His tag NanoAb Targeting Mouse CD47, clone 5023 |
ABN-NAB00020-MF01J | VHH-His tag NanoAb Targeting Mouse CD47, clone 5023 (FITC) |
ABN-NAB00021-M01J | VHH-His tag NanoAb Targeting Mouse CD276, clone 5013 |
ABN-NAB00021-MF01J | VHH-His tag NanoAb Targeting Mouse CD276, clone 5013 (FITC) |
ABN-NAB00022-M01J | VHH-His tag NanoAb Targeting Human EPCAM, clone 6025 |
ABN-NAB00022-MF01J | VHH-His tag NanoAb Targeting Human EPCAM, clone 6025 (FITC) |
ABN-NAB00023-M01J | VHH-His tag NanoAb Targeting Human MSR1, clone E035 |
ABN-NAB00023-MF01J | VHH-His tag NanoAb Targeting Human MSR1, clone E035 (FITC) |
ABN-NAB00024-M01J | VHH-His tag NanoAb Targeting Human TREM2, clone 3038 |
ABN-NAB00024-MF01J | VHH-His tag NanoAb Targeting Human TREM2, clone 3038 (FITC) |
ABN-NAB00025-M01J | VHH-His tag NanoAb Targeting Human CD30, clone 9063 |
ABN-NAB00025-MF01J | VHH-His tag NanoAb Targeting Human CD30, clone 9063 (FITC) |
ABN-NAB00026-M01J | VHH-His tag NanoAb Targeting Human Clostridium difficile enterotoxin B, clone L068 |
ABN-NAB00026-MF01J | VHH-His tag NanoAb Targeting Human Clostridium difficile enterotoxin B, clone L068 (FITC) |
ABN-NAB00027-M01J | VHH-His tag NanoAb Targeting Human DR5, clone 1100 |
ABN-NAB00027-MF01J | VHH-His tag NanoAb Targeting Human DR5, clone 1100 (FITC) |
ABN-NAB00028-M01J | VHH-His tag NanoAb Targeting Mouse TNFR-2, clone I120 |
ABN-NAB00028-MF01J | VHH-His tag NanoAb Targeting Mouse TNFR-2, clone I120 (FITC) |
ABN-NAB00029-M01J | VHH-His tag NanoAb Targeting Mouse CAIX, clone M121 |
ABN-NAB00029-MF01J | VHH-His tag NanoAb Targeting Mouse CAIX, clone M121 (FITC) |
ABN-NAB00030-M01J | VHH-His tag NanoAb Targeting Mouse ASGPR, clone 3133 |
ABN-NAB00030-MF01J | VHH-His tag NanoAb Targeting Mouse ASGPR, clone 3133 (FITC) |
ABN-NAB00031-M01J | VHH-His tag NanoAb Targeting Mouse CSV, clone 3098 |
ABN-NAB00031-MF01J | VHH-His tag NanoAb Targeting Mouse CSV, clone 3098 (FITC) |
ABN-NAB00032-M01J | VHH-His tag NanoAb Targeting Mouse LAG-3, clone C016 |
ABN-NAB00032-MF01J | VHH-His tag NanoAb Targeting Mouse LAG-3, clone C016 (FITC) |
ABN-NAB00033-M01J | VHH-His tag NanoAb Targeting Mouse CD83, clone 4116 |
ABN-NAB00033-MF01J | VHH-His tag NanoAb Targeting Mouse CD83, clone 4116 (FITC) |
ABN-NAB00034-M01J | VHH-His tag NanoAb Targeting Mouse PD-L2, clone 3117 |
ABN-NAB00034-MF01J | VHH-His tag NanoAb Targeting Mouse PD-L2, clone 3117 (FITC) |
ABN-NAB00035-M01J | VHH-His tag NanoAb Targeting Mouse VISTA, clone G119 |
ABN-NAB00035-MF01J | VHH-His tag NanoAb Targeting Mouse VISTA, clone G119 (FITC) |
ABN-NAB00036-M01J | VHH-His tag NanoAb Targeting Mouse GFAP, clone I096 |
ABN-NAB00036-MF01J | VHH-His tag NanoAb Targeting Mouse GFAP, clone I096 (FITC) |
ABN-NAB00037-M01J | VHH-His tag NanoAb Targeting Mouse CD19, clone 3107 |
ABN-NAB00037-MF01J | VHH-His tag NanoAb Targeting Mouse CD19, clone 3107 (FITC) |
ABN-NAB00038-M01J | VHH-His tag NanoAb Targeting Human EGFR, clone 1019 |
ABN-NAB00038-MF01J | VHH-His tag NanoAb Targeting Human EGFR, clone 1019 (FITC) |
ABN-NAB00039-M01J | VHH-His tag NanoAb Targeting Human Varicella zoster virus gE, clone I032 |
ABN-NAB00039-MF01J | VHH-His tag NanoAb Targeting Human Varicella zoster virus gE, clone I032 (FITC) |
ABN-NAB00040-M01J | VHH-His tag NanoAb Targeting Human VEGFR2, clone 4082 |
ABN-NAB00040-MF01J | VHH-His tag NanoAb Targeting Human VEGFR2, clone 4082 (FITC) |
ABN-NAB00041-M01J | VHH-His tag NanoAb Targeting Mouse Glypican 1, clone 1088 |
ABN-NAB00041-MF01J | VHH-His tag NanoAb Targeting Mouse Glypican 1, clone 1088 (FITC) |
ABN-NAB00042-M01J | VHH-His tag NanoAb Targeting Human CD276, clone O014 |
ABN-NAB00042-MF01J | VHH-His tag NanoAb Targeting Human CD276, clone O014 (FITC) |
ABN-NAB00043-M01J | VHH-His tag NanoAb Targeting Human CGRP, clone E070 |
ABN-NAB00043-MF01J | VHH-His tag NanoAb Targeting Human CGRP, clone E070 (FITC) |
ABN-NAB00044-M01J | VHH-His tag NanoAb Targeting Human PCSK9, clone 3076 |
ABN-NAB00044-MF01J | VHH-His tag NanoAb Targeting Human PCSK9, clone 3076 (FITC) |
ABN-NAB00045-M01J | VHH-His tag NanoAb Targeting Human IL6, clone 4139 |
ABN-NAB00045-MF01J | VHH-His tag NanoAb Targeting Human IL6, clone 4139 (FITC) |
ABN-NAB00046-M01J | VHH-His tag NanoAb Targeting Human IFNG, clone 4136 |
ABN-NAB00046-MF01J | VHH-His tag NanoAb Targeting Human IFNG, clone 4136 (FITC) |
ABN-NAB00047-M01J | VHH-His tag NanoAb Targeting Human SOST, clone 1080 |
ABN-NAB00047-MF01J | VHH-His tag NanoAb Targeting Human SOST, clone 1080 (FITC) |
ABN-NAB00048-M01J | VHH-His tag NanoAb Targeting Human RSV, clone UA01 |
ABN-NAB00048-MF01J | VHH-His tag NanoAb Targeting Human RSV, clone UA01 (FITC) |
ABN-NAB00049-M01J | VHH-His tag NanoAb Targeting Mouse PD-L1, clone G003 |
ABN-NAB00050-M01J | VHH-His tag NanoAb Targeting Mouse CD138, clone 3123 |
ABN-NAB00051-M01J | VHH-His tag NanoAb Targeting Mouse CD38, clone 1122 |
ABN-NAB00052-M01J | VHH-His tag NanoAb Targeting Human FX, clone 1112 |
ABN-NAB00053-M01J | VHH-His tag NanoAb Targeting Human CD63, clone 3033 |
ABN-NAB00054-M01J | VHH-His tag NanoAb Targeting Human NGFR, clone 1046 |
ABN-NAB00055-M01J | VHH-His tag NanoAb Targeting Human BLyS, clone 9057 |
ABN-NAB00056-M01J | VHH-His tag NanoAb Targeting Mouse CTLA-4, clone 4018 |
ABN-NAB00057-M01J | VHH-His tag NanoAb Targeting Mouse EpCAM, clone 2124 |
ABN-NAB00058-M01J | VHH-His tag NanoAb Targeting Mouse ICAM, clone 6127 |
ABN-NAB00059-M01J | VHH-His tag NanoAb Targeting Human CD7, clone 6131 |
ABN-NAB00060-M01J | VHH-His tag NanoAb Targeting Mouse OX40, clone 5028 |
ABN-NAB00061-M01J | VHH-His tag NanoAb Targeting Human Adeno-associated virus VP1, clone K102 |
ABN-NAB00062-M01J | VHH-His tag NanoAb Targeting Human CD22, clone 4062 |
ABN-NAB00063-M01J | VHH-His tag NanoAb Targeting Human P-selectin, clone 1079 |
ABN-NAB00064-M01J | VHH-His tag NanoAb Targeting Mouse PSCA, clone 5099 |
ABN-NAB00065-M01J | VHH-His tag NanoAb Targeting Mouse Qa-2 Alpha3 Domain, clone 2004 |
ABN-NAB00066-M01J | VHH-His tag NanoAb Targeting Human ACE2, clone K150 |
ABN-NAB00067-M01J | VHH-His tag NanoAb Targeting Human CD33, clone D064 |
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