Abnova：VHH抗體

發(fā)布者：艾美捷科技發(fā)布時間：2025-02-20

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介紹

癌癥仍然是全球最緊迫的健康挑戰(zhàn)之一，標準治療如手術(shù)、放療和化療往往未能完全根除腫瘤細胞。免疫治療的進步突出了免疫系統(tǒng)在識別和摧毀癌細胞中的關(guān)鍵作用。然而，腫瘤微環(huán)境（TMEs）創(chuàng)造了諸如缺氧、酸性和免疫逃逸機制等障礙，阻礙了治療效果。VHH抗體作為癌癥免疫治療中的一個有前途的工具正在出現(xiàn)。它們的小規(guī)格、高穩(wěn)定性和特異性使它們能夠有效地靶向腫瘤并激活免疫反應，為創(chuàng)新的細胞介導的癌癥療法鋪平了道路。

VH抗體特征

小規(guī)格：能夠穿透致密組織并跨越如血腦屏障等障礙。

高穩(wěn)定性：在極端條件下保持功能，包括高溫、酸性環(huán)境和放療。

卓越的特異性和親和力：精確靶向傳統(tǒng)抗體無法接近的隱藏表位。

低免疫原性：減少免疫反應和非靶向效應，促進治療安全性。

多功能工程：易于與藥物、同位素或納米顆粒結(jié)合；支持體內(nèi)或體外系統(tǒng)的大規(guī)模生產(chǎn)。

改善的溶解性：增強非侵入性治療的生物利用度和安全性。

常規(guī)單抗和重鏈抗體

細胞介導的免疫治療應用

BsAb藥物旨在以不同方式發(fā)揮作用。策略包括：

1. 阻斷抑制性受體

VHH抗體提供了一種針對性方法來對抗腫瘤或T細胞上的抑制性受體，如PD-L1和CTLA-4。它們有效的組織穿透和精確結(jié)合恢復免疫功能并防止腫瘤逃逸。

——示例——

幾項研究表明，靶向PD-L1、CXCR4和CD47的VH抗體可以有效地阻斷腫瘤細胞上的這些受體并增強對癌癥的免疫反應。

2. 橋接腫瘤和免疫細胞

VH抗體提供了一種新穎的方法來橋接腫瘤和免疫細胞，通過克服癌細胞使用的免疫逃逸機制，如抑制免疫反應和下調(diào)MHC分子。這些多功能劑可以靶向T細胞和自然殺傷（NK）細胞，增強它們對腫瘤的活性，同時最小化與傳統(tǒng)單克隆抗體相關(guān)的副作用。

——示例——

基于HER2/CD3的VH抗體的雙特異性酶（BiTEs）增強T細胞激活和腫瘤殺傷。

基于HER2/CD16VH抗體的雙特異性酶（BiKEs）增強NK細胞反應，幫助腫瘤根除。

3.使用VH抗體結(jié)合CAR免疫細胞靶向腫瘤細胞

嵌合抗原受體（CAR）療法，包括CAR-T和CAR-NK細胞，結(jié)合了基因工程與過繼細胞療法，并已在治療血液癌癥中顯示出成功。傳統(tǒng)上，抗原靶向域來源于單克隆抗體（mAbs）的單鏈片段（scFv）。最近，VH抗體因其一些優(yōu)勢如小尺寸、穩(wěn)定性、高特異性和易于開發(fā)而成為替代品。研究表明，VH抗體結(jié)合的CAR免疫細胞在臨床前和臨床研究中的表現(xiàn)與scFv基CAR-T細胞相當。

不同類型的基于VH抗體的CAR-T細胞

單特異性CAR-T細胞：這些CAR-T細胞設計為靶向癌細胞上的單一腫瘤相關(guān)抗原（TAA）。

雙特異性CAR-T細胞：這些CAR-T細胞識別同一抗原上的兩個不同表位。這種設計增強了結(jié)合強度（親和力）并減少了抗原逃逸的可能性。

寡克隆CAR-T細胞：寡克隆CAR-T細胞由混合的CAR-T細胞群組成，每個細胞靶向不同的抗原。這種方法通過同時靶向多個TAAs解決了腫瘤異質(zhì)性問題，降低了抗原丟失變異的風險。

雙特異性和三特異性CAR-T細胞：這些CAR-T細胞被設計為識別兩個或三個不同的TAAs。通過同時靶向多個抗原，它們增強了特異性并減輕了由于抗原丟失導致的腫瘤逃逸。

通用CAR-T細胞：通用CAR-T細胞被設計為廣泛適用性和靈活性。它們通常使用模塊化系統(tǒng)，如通用受體結(jié)合適配分子，可以重新編程以靶向不同的抗原。

——示例——

功能類型	目標	CAR結(jié)構(gòu)	腫瘤類型	參考
單特異性	BCMA	BCMA.Nb-CD8a-CD8aTM-4-1BB-CD3ζ	Hematologic malignancies	Han L, et al., (2020)
雙表位	BCMA	BCMA.Nb-BCMA.Nb-CD8a-CD8aTM-4-1BB-CD3ζ	Hematologic malignancies	Zhao W-H, et al. (2018)
寡克隆	HER2	HER2.Nb-IgG3-Fc&Hinge-CD28-CD28-CD3ζ HER2.Nb-IgG3-Fc&Hinge-Hinge-CD28-CD28-CD3ζ HER2.Nb-IgG3-Fc&Hinge-CD28-CD28-OX40-CD3ζ HER2.Nb-IgG3-Fc&Hinge-Hinge-CD28-CD28-OX40-CD3ζ	Solid tumor	Jamnani FR, et al. (2014)
雙特異性	CD20&HER2	CD20.Nb-IgG1-Fc-CD28TM-CD28-CD3ζ HER2.Nb-IgG1-Fc-CD28TM-CD28-CD3ζ CD20.Nb-HER2.Nb-IgG1-Fc-CD28TM-CD28-CD3ζ	Solid tumor	De Munter S, et al. (2018)
雙特異性和分裂	CD13&TIM3	Nb-IgG4mutant (IgG4m) hinge- CD8TM- 4-1BB, and CD3ζ CD13.Nb-CD3z, TIM3.scFv-CD28-4-1BB	Hematologic malignancies	He X, et al., (2020)
三特異性	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? 產(chǎn)品

NanoAb? 服務

VHH 雙特異性抗體服務

VHH nanoBiTE? 服務

nanoCAR-T mRNA 服務

貨號	產(chǎn)品名稱
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