Abstract
Immunotherapy has been considered as one of the most promising strategies for protection against cancer cells due to the tremendous advantages arising from host immune defense. However, establishing versatile strategies with high biosafety and the capability for efficient modulation of immune responses remains challenging. The structural features resembling native proteins of peptides bestow their great potential to address these challenges via either directly eliciting immune responses or improving the efficacy of therapeutics. This review summarizes the progress of cancer immunotherapy achieved based on the strategies utilizing short peptides as therapeutic agents or peptide assemblies as delivery scaffolds, beyond long sequences like proteins and polypeptides. Starting from a brief introduction of cancer immunotherapy, we outline the peptide sequences in terms of their specific functions including immune checkpoint blockades, vaccine antigens and adjuvants. We particularly high-light peptide-based nanomaterials as scaffolds for targeting delivery or co-delivery of multiple therapeutics to enhance immunogenicity. The extraordinary therapeutic efficacy of the limited examples covered here demonstrates the great potency of the peptide-based strategies in modulating immune responses, thus potentially facilitating the clinical translation of cancer immunotherapy in the future.
摘要
基于通过激活宿主天然免疫应答杀死癌症细胞的优势, 免疫治疗被认为有望成为癌症治疗的新方法. 与传统治疗方法相比, 免疫治疗能够诱导长期的免疫记忆以预防癌症复发和转移, 具有更广谱的抗癌效果以及较小的副作用. 然而建立具有高生物安全性和免疫应答能力的策略仍然具有挑战性. 由于其与天然蛋白质类似的结构特征, 多肽分子有望通过直接引发免疫应答或改善药物递送效果来解决这些挑战. 本文总结了过去十年内发现的利用短肽分子作为免疫治疗药物或递送平台的癌症免疫疗法. 从简要介绍癌症免疫治疗开始, 我们概述了多肽分子的特定药物功能, 包括免疫检查点抑制剂、 疫苗抗原和佐剂. 随后着重介绍了基于多肽纳米结构作为递送平台, 用于药物靶向递送或多种药物共同递送以增强免疫原性的进展. 最后对基于多肽的癌症免疫治疗面临的挑战以及未来的发展趋势进行了展望.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (21774065), the Fundamental Research Funds for the Central Universities, and the Natural Science Foundation of Tianjin (18JCQNJC14100).
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Li M prepared the manuscript under the guidance of Yu Z. Li M and Zhao X designed and prepared the figures. Yu Z and Dai J revised the manuscript. All authors contributed to the general discussion and revision of the manuscript.
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The authors declare no conflict of interest.
Mingming Li received her Master degree in chemical engineering from China University of Petroleum (Beijing) in 2018. Currently she is a PhD candidate under the supervision of Prof. Zhilin Yu at the Institute of Polymer Chemistry of Nankai University. Her current research interest lies in the field of stimulus-responsive peptide self-assembly and the biomaterials including drug delivery and disease therapy.
Zhilin Yu was awarded his PhD degree under the supervision of Prof. Stefan Hecht at the Humboldt-Universität zu Berlin in 2013. He conducted his postdoctoral training with Prof. Samuel I. Stupp at Northwestern University focusing on self-assembly of peptide-based amphiphilic molecules. In 2017, he started his independent career at the Institute of Polymer Science of Nankai University. His current research interests focus on the self-assembly of peptides into dynamic nanostructures and their broad applications as biomaterials including disease diagnosis and therapy.
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Li, M., Zhao, X., Dai, J. et al. Peptide therapeutics and assemblies for cancer immunotherapy. Sci. China Mater. 62, 1759–1781 (2019). https://doi.org/10.1007/s40843-019-9451-7
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DOI: https://doi.org/10.1007/s40843-019-9451-7