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调动固有免疫靶向表皮生长因子受体:利用固有免疫对比适应性免疫对比信号抑制的治疗选择

英文原题:Engaging innate immunity for targeting the epidermal growth factor receptor: Therapeutic options leveraging innate immunity versus adaptive immunity versus inhibition of signaling.

查看英文原题

Engaging innate immunity for targeting the epidermal growth factor receptor: Therapeutic options leveraging innate immunity versus adaptive immunity versus inhibition of signaling.

PubMed 2022/09/14(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

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中文摘要

表皮生长因子受体(EGFR)在正常组织生理和癌症病理过程中均发挥关键作用。目前已有多种治疗方法用于靶向部分肿瘤中的EGFR致癌性基因改变,以及利用肿瘤中EGFR过表达这一特征。靶向EGFR活化的小分子抑制剂和抗EGFR抗体,为EGFR突变或野生型表达的癌症患者提供了有效但有限的治疗选择;而调动适应性或先天免疫效应细胞的治疗仍在开发中。本文讨论通过不同分子机制靶向EGFR、杀伤EGFR表达癌细胞的疗法,重点比较抑制EGFR活化的治疗与利用细胞毒性T细胞和先天免疫细胞攻击EGFR阳性癌细胞的策略及其成败。此外,我们探讨可能克服现有疗法局限的替代方案,尤其关注先天免疫细胞衔接器。本文还强调,将先天免疫细胞衔接器与免疫疗法联合以增强疗效,或与非特异性细胞疗法联合以使其转变为肿瘤特异性疗法的潜力。

展开英文摘要原文

The epidermal growth factor receptor (EGFR) is a key player in the normal tissue physiology and the pathology of cancer. Therapeutic approaches have now been developed to target oncogenic genetic aberrations of EGFR, found in a subset of tumors, and to take advantage of overexpression of EGFR in tumors. The development of small-molecule inhibitors and anti-EGFR antibodies targeting EGFR activation have resulted in effective but limited treatment options for patients with mutated or wild-type EGFR-expressing cancers, while therapeutic approaches that deploy effectors of the adaptive or innate immune system are still undergoing development.

This review discusses EGFR-targeting therapies acting through distinct molecular mechanisms to destroy EGFR-expressing cancer cells. The focus is on the successes and limitations of therapies targeting the activation of EGFR versus those that exploit the cytotoxic T cells and innate immune cells to target EGFR-expressing cancer cells.

Moreover, we discuss alternative approaches that may have the potential to overcome limitations of current therapies; in particular the innate cell engagers are discussed.

Furthermore, this review highlights the potential to combine innate cell engagers with immunotherapies, to maximize their effectiveness, or with unspecific cell therapies, to convert them into tumor-specific agents.

论文信息

作者
Hintzen G、Dulat HJ、Rajkovic E
单位
Research and Development, Affimed GmbH, Heidelberg, Germany.Germany
文献类型
综述
期刊
Frontiers in oncology2022
原文标识
PubMed 36185288 · DOI 10.3389/fonc.2022.892212