免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Harnessing SARS-CoV-2 immunity to promote antitumor responses through intratumoral vaccination and adoptive transfer.
Harnessing SARS-CoV-2 immunity to promote antitumor responses through intratumoral vaccination and adoptive transfer.
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这些发现提供了概念验证,即在存在预先抗病毒免疫的情况下,瘤内接种 SARS-CoV-2 疫苗可通过局部免疫激活促进抗肿瘤效应。该策略可能为后疫情时代增强瘤内免疫治疗提供一种可转化的方法。
癌症免疫疗法通过调动免疫系统,为恶性肿瘤的治疗带来了希望;然而,对于缺乏免疫浸润的肿瘤,其疗效仍然有限。因此,需要创新性策略将这些免疫学上的“冷”肿瘤转化为更易受免疫介导攻击的“热”肿瘤。治疗性疫苗正是这样一种策略,能够触发强效的免疫激活和持久的记忆反应。鉴于全球绝大多数人口要么接种过SARS-CoV-2疫苗,要么接触过该病毒,我们假设可以利用预先存在的抗病毒免疫在局部增强肿瘤内免疫反应。
为验证这一概念,我们在B16F10小鼠黑色素瘤模型中评估了瘤内SARS-CoV-2疫苗接种的治疗效果,使用了两种SARS-CoV-2疫苗平台:pVAX-SARS-S,一种编码刺突蛋白S1亚基的DNA疫苗;以及rAd-SARS2-S1/CD40L,一种表达分泌型S1-CD40L融合蛋白的重组腺病毒。荷瘤C57BL/6小鼠接受瘤内疫苗接种,分别在有或无预先免疫的情况下进行,预先免疫于六个月前建立,以模拟既有的抗病毒免疫。
瘤内接种 pVAX-SARS-S 显著降低了初始小鼠和预免疫小鼠的肿瘤负荷并延长了生存期。其抗肿瘤保护作用可通过脾细胞过继转移,表明系统性适应性免疫参与了肿瘤排斥的介导。rAd-SARS2-S1/CD40L 平台提供了适度的肿瘤控制。虽然两种疫苗均有效,但 DNA 平台表现出更优的疗效。
To test this concept, we evaluated the therapeutic efficacy of intratumoral SARS-CoV-2 vaccination in the B16F10 murine melanoma model using two SARS-CoV-2 vaccine platforms: pVAX-SARS-S, a DNA vaccine encoding the spike protein S1 subunit and rAd-SARS2-S1/CD40L, a recombinant adenovirus expressing a secreted S1-CD40L fusion protein. Tumor-bearing C57BL/6 mice were treated intratumorally with either vaccine in the presence or absence of prior immunization, which had been established six months earlier to mimic pre-existing antiviral immunity.
Intratumoral vaccination with pVAX-SARS-S significantly reduced tumor burden and prolonged survival in both naïve and pre-immunized mice. Its antitumor protection could be adoptively transferred via splenocytes, indicating the involvement of systemic adaptive immunity in mediating tumor rejection. The rAd-SARS2-S1/CD40L platform conferred modest tumor control. While both vaccines were effective, the DNA platform demonstrated superior efficacy. DISCUSSION: Together, these findings provide proof-of-concept that intratumoral administration of SARS-CoV-2 vaccines can promote antitumor effects through local immune activation in the context of pre-existing antiviral immunity. This strategy may offer a translatable approach for enhancing intratumoral immunotherapy in the post-pandemic era.
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