一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Combinational Pulsing of TAAs Enforces Dendritic Cell-Based Immunotherapy through T-Cell Proliferation and Interferon-γ Secretion in LLC1 Mouse Model.
Combinational Pulsing of TAAs Enforces Dendritic Cell-Based Immunotherapy through T-Cell Proliferation and Interferon-γ Secretion in LLC1 Mouse Model.
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NSCLC 是最常见的肺癌类型,由于早期症状轻微,常被晚期诊断。化疗后复发或转移的高风险使基于 DC 的免疫治疗成为一种有前景的策略,其能够靶向破坏癌症、副作用低、形成记忆,并克服癌症的免疫逃逸能力。
然而,负载单一抗原的 DC 应答有限仍是一个重大挑战。为克服这一问题,我们通过负载 TAAs 增强 DC 抗原呈递。我们的研究聚焦于通过联合负载 TAAs 增强 DC 介导免疫应答的特异性和强度,所选 TAAs 基于其在 NSCLC 中的高流行性。
我们选择了在 NSCLC 中表达的四种 TAAs,并以最佳组合负载 DC。随后,我们将负载 TAAs 的 DC 注入 LLC1 小鼠模型,以评估其抗肿瘤疗效。
我们的结果显示,负载 TAAs 的 DC 显著缩小了肿瘤体积并促进了肿瘤组织中的凋亡。此外,与未负载的 DC 相比,负载 TAAs 的 DC 显著增加了脾脏中的总 T 细胞。
另外,对来自负载 TAAs 的 DC 的脾细胞进行体外刺激,显示出显著的 T 细胞增殖和 IFN-γ 分泌增加。我们的发现表明,多重 TAA 负载具有增强 DC 抗原呈递能力的潜力,从而加强对肿瘤的免疫应答。
NSCLC, the most common type of lung cancer, is often diagnosed late due to minimal early symptoms. Its high risk of recurrence or metastasis post-chemotherapy makes DC-based immunotherapy a promising strategy, offering targeted cancer destruction, low side effects, memory formation, and overcoming the immune evasive ability of cancers.
However, the limited response to DCs pulsed with single antigens remains a significant challenge. To overcome this, we enhanced DC antigen presentation by pulsing with TAAs.
Our study focused on enhancing DC-mediated immune response specificity and intensity by combinatorial pulsing of TAAs, selected for their prevalence in NSCLC.
We selected four types of TAAs expressed in NSCLC and pulsed DCs with the optimal combination. Next, we administered TAAs-pulsed DCs into the LLC1 mouse model to evaluate their anti-tumor efficacy.
Our results showed that TAAs-pulsed DCs significantly reduced tumor size and promoted apoptosis in tumor tissue.
Moreover, TAAs-pulsed DCs significantly increased total T cells in the spleen compared to the unpulsed DCs.
Additionally, in vitro stimulation of splenocytes from the TAAs-pulsed DCs showed notable T-cell proliferation and increased IFN-γ secretion.
Our findings demonstrate the potential of multiple TAA pulsing to enhance the antigen-presenting capacity of DCs, thereby strengthening the immune response against tumors.
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