基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
hmLIGHT 通过促进 T 细胞浸润和激活增强 4T1 乳腺癌模型中的疫苗抗肿瘤效果
英文原题：hmLIGHT Enhances Vaccine Antitumor Effects by Facilitating T-cell Infiltration and Activation in the 4T1 Breast Cancer Model.
查看英文原题
hmLIGHT Enhances Vaccine Antitumor Effects by Facilitating T-cell Infiltration and Activation in the 4T1 Breast Cancer Model.
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中文摘要
越来越多的证据表明，免疫疗法是抗击癌症的有前景的策略。然而，免疫抑制性肿瘤微环境（TME）、淋巴细胞浸润不足以及免疫原性差阻碍了免疫疗法的更广泛应用。LIGHT 是 TNF 超家族的一员，已被证明可将 T 细胞募集到 TME 中，将“冷”肿瘤转变为“热”肿瘤。
在此，我们获得了一种人突变型 LIGHT（hmLIGHT）蛋白，该蛋白通过不依赖 CD28 的共刺激活性成功促进了小鼠 CD8+ T 细胞的活化和增殖。
此外，直接瘤内注射 VR-hmLIGHT 重塑了 TME，增强了 CD8+ T 细胞向肿瘤的浸润，并在 4T1 和 CT26 肿瘤模型中显示出抗肿瘤疗效。
此外，我们先前对 DNA 疫苗（OsFS）的研究已显示出有前景的抗肿瘤活性。在本研究中，我们评估了 VR-hmLIGHT 与 OsFS 的新联合方案在 4T1 肿瘤模型中的增效作用。联合治疗具有显著的抗肿瘤效果，肿瘤抑制率为 70%，而 OsFS 组和 VR-hmLIGHT 组分别显示 32% 和 42% 的抑制率。这些发现表明 LIGHT 作为单一疗法或联合疗法的临床潜力。
展开英文摘要原文
Mounting evidence suggests that immunotherapies are promising strategies for fighting against cancers.
However, the immunosuppressive tumor microenvironment (TME), insufficient lymphocytic infiltration, and poor immunogenicity hamper the broader implementation of immunotherapies. LIGHT, a member of the TNF superfamily, has been shown to recruit T cells into the TME, turning "cold" tumors into "hot" ones.
Here, a human mutant LIGHT (hmLIGHT) protein has been obtained which successfully promoted the activation and proliferation of mouse CD8+ T cells via CD28-independent co-stimulatory activity.
Moreover, direct intratumoral injection of VR-hmLIGHT remodeled the TME, enhanced CD8+ T-cell infiltration into tumors, and showed antitumor efficacy in 4T1 and CT26 tumor models.
In addition, our previous studies of a DNA vaccine (OsFS) have shown promising antitumor activity. In this study, we evaluated a new combination of VR-hmLIGHT and OsFS to enhance efficacy in the 4T1 tumor model. The combined treatment has a remarkable antitumor effect, with a tumor inhibition rate of 70%, whereas OsFS and VR-hmLIGHT groups displayed 32% and 42% inhibition, respectively.
These findings indicate the clinical potential of LIGHT as monotherapy or combination therapy.
论文信息
- 作者
- Dong L、Zhang S、Wuri Q、Qu X、Zhang K、Cai Z、Qiao Y、Feng M
- 单位
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P. R. China.China
- 期刊
- Molecular cancer therapeutics2025 Sep 2
- 原文标识
- PubMed 40066767 · DOI 10.1158/1535-7163.MCT-24-0333