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
英文原题:Novel immune targets for the treatment of triple-negative breast cancer.
Novel immune targets for the treatment of triple-negative breast cancer.
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在 TNBC 中已经研究了多种免疫策略,包括 PD1-PD-L1 轴之外的共抑制分子、共刺激检查点、癌症疫苗、过继性细胞转移、联合治疗以及不同的给药途径。大多数方法在早期临床试验中显示出抗癌活性和良好的安全性。由于迄今为止 IO 仅使一小部分 TNBC 患者获益,识别预测性生物标志物是优化患者筛选的优先事项。正在进行的临床试验数据,随着对乳腺肿瘤免疫环境解读的逐步改善,有望明确新的免疫靶点在 TNBC 治疗中的作用。
为克服抗肿瘤免疫应答的原发性和继发性耐药机制,目前正在临床前和早期临床阶段探索ICOS、LAG3和TIM3等新靶点。涵盖领域:本文探讨了在TNBC早期临床试验中研究的免疫治疗药物的全景。针对每个免疫靶点,提供了临床前依据、主要表达情况和功能。讨论了临床意义和初步可获得的试验结果,最后,我们反思了该领域的未来期望和挑战。
INTRODUCTION: To overcome mechanisms of primary and secondary resistance to the anti-tumor immune response, novel targets such as ICOS, LAG3, and TIM3 are currently being explored at preclinical and early-phase clinical levels. AREAS COVERED: This article examines the landscape of the immune therapeutics investigated in early-phase clinical trials for TNBC. Preclinical rationale is provided for each immune target, predominant expression, and function. Clinical implications and preliminary available trial results are discussed and finally, we reflect on aspects of future expectations and challenges in this field.
EXPERT OPINION: Several immune strategies have been investigated in TNBC, including co-inhibitory molecules beyond PD1-PD-L1 axis, co-stimulatory checkpoints, cancer vaccines, adoptive cell transfer, combination therapies, as well as different routes of administration. Most of approaches showed signs of anti-cancer activity and a good safety profile in early-phase clinical trials.
Since IO provided benefit only to a small subgroup of TNBC patients so far, identifying predictive biomarkers is a priority to refine patient-selection. Data from ongoing clinical trials, with the gradually improving interpretation of the breast tumor immune environment, will hopefully refine the role of new immune targets for the treatment of TNBC.
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