Abnova VHH抗體在細(xì)胞介導(dǎo)的癌癥免疫治療中的應(yīng)用

發(fā)布者：艾美捷科技發(fā)布時(shí)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(biāo)準(zhǔn)治療如手術(shù)、放療和化療往往未能完全根除腫瘤細(xì)胞。免疫治療的進(jìn)步突出了免疫系統(tǒng)在識(shí)別和摧毀癌細(xì)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(jī)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(gè)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(yīng)，為創(chuàng)新的細(xì)胞介導(dǎo)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(wú)法接近的隱藏表位。

低免疫原性：減少免疫反應(yīng)和非靶向效應(yīng)，促進(jìn)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(qiáng)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(xì)胞介導(dǎo)的免疫治療應(yīng)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(duì)性方法來(lái)對(duì)抗腫瘤或T細(xì)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(fù)免疫功能并防止腫瘤逃逸。

——示例——

幾項(xiàng)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(xì)胞上的這些受體并增強(qiáng)對(duì)癌癥的免疫反應(yīng)。

2. 橋接腫瘤和免疫細(xì)胞

VH抗體提供了一種新穎的方法來(lái)橋接腫瘤和免疫細(xì)胞，通過(guò)克服癌細(xì)胞使用的免疫逃逸機(jī)制，如抑制免疫反應(yīng)和下調(diào)MHC分子。這些多功能劑可以靶向T細(xì)胞和自然殺傷（NK）細(xì)胞，增強(qiáng)它們對(duì)腫瘤的活性，同時(shí)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(qiáng)T細(xì)胞激活和腫瘤殺傷。

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

3.使用VH抗體結(jié)合CAR免疫細(xì)胞靶向腫瘤細(xì)胞

嵌合抗原受體（CAR）療法，包括CAR-T和CAR-NK細(xì)胞，結(jié)合了基因工程與過(guò)繼細(xì)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(lái)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(shì)如小尺寸、穩(wěn)定性、高特異性和易于開(kāi)發(fā)而成為替代品。研究表明，VH抗體結(jié)合的CAR免疫細(xì)胞在臨床前和臨床研究中的表現(xiàn)與scFv基CAR-T細(xì)胞相當(dāng)。

不同類型的基于VH抗體的CAR-T細(xì)胞

單特異性CAR-T細(xì)胞：這些CAR-T細(xì)胞設(shè)計(jì)為靶向癌細(xì)胞上的單一腫瘤相關(guān)抗原（TAA）。

雙特異性CAR-T細(xì)胞：這些CAR-T細(xì)胞識(shí)別同一抗原上的兩個(gè)不同表位。這種設(shè)計(jì)增強(qiáng)了結(jié)合強(qiáng)度（親和力）并減少了抗原逃逸的可能性。

寡克隆CAR-T細(xì)胞：寡克隆CAR-T細(xì)胞由混合的CAR-T細(xì)胞群組成，每個(gè)細(xì)胞靶向不同的抗原。這種方法通過(guò)同時(shí)靶向多個(gè)TAAs解決了腫瘤異質(zhì)性問(wèn)題，降低了抗原丟失變異的風(fēng)險(xiǎn)。

雙特異性和三特異性CAR-T細(xì)胞：這些CAR-T細(xì)胞被設(shè)計(jì)為識(shí)別兩個(gè)或三個(gè)不同的TAAs。通過(guò)同時(shí)靶向多個(gè)抗原，它們?cè)鰪?qiáng)了特異性并減輕了由于抗原丟失導(dǎo)致的腫瘤逃逸。

通用CAR-T細(xì)胞：通用CAR-T細(xì)胞被設(shè)計(jì)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(biāo)	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(wù)

VHH 雙特異性抗體服務(wù)

VHH nanoBiTE? 服務(wù)

nanoCAR-T mRNA 服務(wù)

貨號(hào)	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