Immunotherapy maintains the cancer-immunity cycle via re-activating the immune system, so as to achieve the purpose of anti-tumor. However, the response rate of current tumor immunotherapy strategies is still low. Even the most reported immune checkpoint block (ICB), the objective response rate (ORR) is only about 10-30%. Here, aiming at obtaining a higher response rate, we designed a cascade amplification nanocomposite consisting of the immune adjuvant polyinosinic:polycytidylic acid [Poly (I:C)] and aggregation-induced emission luminogen (AIEgen)-modified modular peptide (named PMRA). The PMRA includes: (D)PPA-1 peptide (P), an immune checkpoint inhibitor; PLGLAG peptide (M), a matrix metalloproteinase 2 (MMP-2) responsive sequence to promote the release of (D)PPA-1; RRRRRRRR peptide (R), for loading the Poly (I:C); PyTPA (A), a photosensitizer with AIE property. In cancer-immunity cycle, photodynamic therapy (PDT) mediated by PyTPA promotes the release of tumor-associated antigens (TAAs), and primes T lymphocytes. The cytokines coming from the stimulation of PDT and Poly (I:C) promote the activation of T lymphocytes. The high level of chemokines in tumor microenvironment promotes immune cells migration and infiltration in tumor with the assistance of PDT. Finally, through ICB with (D)PPA-1 peptide, T lymphocytes enhance the recognition of tumor cells and killing tumor cells. Immunogenic cell death induces the release of more TAAs, which will enter the next cycle and complete the full loop again. Taking advantages of whole cancer-immunity cycle, the cascade amplification nanocomposite achieved almost 100% ORR in vivo. This concept of whole cancer-immunity cycle enhanced immunotherapy provides a novel perspective for tumor treatment.
基金:
National Key R&D Program of China [2020YFA0211200]; National Natural Science Foundation of China [22090050, 21974128, 21874121, 52003257, 21703210, 22104040]; Natural Science Foundation of Hubei Province [2019CFA043, 2020CFA037]; Open Research Fund of State Key Laboratory of Bioelectronics
第一作者单位:[1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Obstet & Gynecol, Wuhan 430030, Peoples R China
通讯作者:
推荐引用方式(GB/T 7714):
Dai Jun,Dong Xiaoqi,Liu Rui,et al.A peptide-AIEgen nanocomposite mediated whole cancer immunity cycle-cascade amplification for improved immunotherapy of tumor[J].BIOMATERIALS.2022,285:doi:10.1016/j.biomaterials.2022.121528.
APA:
Dai, Jun,Dong, Xiaoqi,Liu, Rui,Chen, Biao,Dong, Xiyuan...&Lou, Xiaoding.(2022).A peptide-AIEgen nanocomposite mediated whole cancer immunity cycle-cascade amplification for improved immunotherapy of tumor.BIOMATERIALS,285,
MLA:
Dai, Jun,et al."A peptide-AIEgen nanocomposite mediated whole cancer immunity cycle-cascade amplification for improved immunotherapy of tumor".BIOMATERIALS 285.(2022)