抗肿瘤疫苗疗效取决于佐剂类型，并与诱导产生的 IgG 亚类及糖基化谱相关

英文原题：Anti-tumor vaccine efficacy depends on adjuvant type and associates with induced IgG subclass and glycosylation profiles.

查看英文原题

Anti-tumor vaccine efficacy depends on adjuvant type and associates with induced IgG subclass and glycosylation profiles.

PubMed 2025/10/06（内容时间） Exp Hematol Oncol Q1 · IF 17.5（JCR 2025）

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中文摘要

肿瘤（新）抗原联合佐剂接种正在成为有前景的癌症治疗方法。然而，不同佐剂会诱导不同免疫细胞和抗体应答，如何选择合适佐剂仍具挑战。

本研究评估了多种疫苗佐剂在小鼠中预防肿瘤生长的效果，并分析其与IgG亚类及Fc区N-糖基化应答的关系。所用佐剂包括明矾、Toll样受体激动剂Poly(I:C)和MPLA、明矾-Poly(I:C)，以及炎症性油包水佐剂Montanide、IFA、CFA和富含结核分枝杆菌的eCFA。明矾和Montanide未能提供保护；MPLA和IFA呈保护趋势；Poly(I:C)、明矾-Poly(I:C)、CFA和eCFA则显著抑制肿瘤生长。

总体而言，各佐剂诱导高活化型IgG2(c/b)抗体和去岩藻糖基化（F0）IgG1抗体与肿瘤保护相关，后者最高约占5%。虽然所有佐剂在初次免疫后短暂诱导IgG1 F0，但Poly(I:C)和eCFA诱导的记忆应答在无佐剂再次接触抗原后仍能产生IgG1 F0。

此外，Poly(I:C)诱导的肿瘤保护与较高IgG2c/IgG1比值、IgG半乳糖基化和唾液酸化水平，以及产生IFN-γ的CD8+ Tc1细胞相关。相反，Ova-eCFA诱导的肿瘤保护还与各亚类IgG总量较高、半乳糖基化和唾液酸化水平较低，以及CD8+ Tc17和CD4+ Th17细胞相关。

因此，具有保护作用的佐剂既可能诱导共同的保护性程序，也可能诱导不同机制。肿瘤抗原特异性IgG2a单克隆抗体在去半乳糖基化形式和半乳糖基化并唾液酸化形式下均可抑制肿瘤生长，提示可能存在共同和不同的保护机制。Poly(I:C)免疫小鼠血清转移所产生的肿瘤保护更依赖NK细胞，而eCFA诱导的抗体以及非唾液酸化、非半乳糖基化单抗可促进中性粒细胞活化。这些发现可能有助于改进肿瘤疫苗方案。

展开英文摘要原文

Vaccination with tumor-(neo) antigen plus adjuvant is emerging as a promising cancer-therapy.

However, as different adjuvants induce distinct immune cell and antibody (Ab) responses, selecting the right adjuvants remains challenging.

Here, we evaluated the following vaccine adjuvants to promote protection against tumor-growth in mice and correlated IgG subclass and Fc N-glycosylation responses: Alum; the toll-like receptor activators Poly(I:C) and MPLA; Alum-Poly(I:C); and the more inflammatory water-in-oil adjuvants Montanide, IFA, CFA, and M. tb. -enriched (e)CFA. While Alum and Montanide failed to protect, MPLA and IFA tended to protect, and Poly(I:C), Alum-Poly(I:C), CFA, and eCFA significantly protected against tumor-growth.

Across all adjuvants, tumor-protection correlated with the induction of highly activating IgG2(c/b) Abs and afucosylated (F0) IgG1 Abs, the latter showing up to 5% abundance. While all adjuvants transiently induced IgG1 F0 following initial immunization, Poly(I:C)- and eCFA-induced memory responses also generated IgG1 F0 after repeated antigen-exposure without adjuvants.

Additionally, Poly(I:C)-induced tumor-protection was associated with high IgG2c/IgG1 ratios, high levels of IgG galactosylation and sialylation, and IFN -producing CD8 + Tc1-cells. Conversely, Ova-eCFA-induced tumor-protection was additionally associated with high levels of IgG across all subclasses, but low levels of galactosylation and sialylation, and CD8 + Tc17- and CD4 + Th17-cells. Accordingly, tumor protecting adjuvants may induce common but also different protecting programs.

A tumor-antigen-specific IgG2a monoclonal (m)Ab protected against tumor-growth in both its de-galactosylated and galactosylated plus sialylated forms, suggesting common and possibly distinct protective mechanisms. Tumor-protection via serum transfer from Poly(I:C)-immunized mice depended more on NK-cells, whereas eCFA-induced and non-sialylated/non-galactosylated mAbs promoted neutrophil activation.

These findings may help to improve tumor vaccination protocols.

论文信息

作者: Lehrian S、Wasynczuk A、Petry J、Guderian M、Nouta J、Buhre JS、Lunding HB、Köcher P
第一作者单位: Laboratory of Immunology, Institute of Nutritional Medicine, University of Lübeck and University Hospital Schleswig-Holstein, Ratzeburger Allee 160, 23562, Lübeck, Germany.Germany
通讯作者单位: Laboratory of Immunology, Institute of Nutritional Medicine, University of Lübeck and University Hospital Schleswig-Holstein, Ratzeburger Allee 160, 23562, Lübeck, Germany. marc.ehlers@uksh.de.Germany
文献类型: 读者来信
期刊: Experimental hematology & oncology2025 Oct 6

原文标识: PubMed 41053886　·　DOI 10.1186/s40164-025-00708-6

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