TY - JOUR
T1 - Tumor-Targeted Delivery of IL-2 by Fusing with a pH Low Insertion Peptide for Antitumor Immunotherapy
AU - Chu, Tianjiao
AU - Cao, Bowei
AU - Wang, Peina
AU - Li, Bozhao
AU - Ren, Jinna
AU - Nie, Guangjun
AU - Wei, Jingyan
AU - Li, Suping
N1 - Funding Information:
This study was supported by grants from the Beijing Distinguished Young Scientist program (JQ20037 to S.L.), the Key Area R&D Program of Guangdong Province (2020B0101020004 to S.L.), the National Basic Research Plan of China (2018YFE0205300 to S.L. and 2018YFA0208900 to G.N.), and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB36000000 to G.N.).
Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/10/18
Y1 - 2023/10/18
N2 - As a pleiotropic cytokine, interleukin-2 (IL-2) can effectively regulate lymphocyte proliferation, survival, and active antitumor immune responses in tumor microenvironments. Although the ability of IL-2 to boost immune responses was reported in cancer patients, its short circulating half-life and high toxicity hinder its broad and continual clinical application. Herein, we developed a novel tumor target agent by fusing pH low insertion peptides (pHLIP) with IL-2, forming the fusion protein pHLIP-IL2. Based on the low pH insertion property of pHLIP, the pHLIP-IL2 fusion protein could be selectively delivered to the acidic tumor microenvironments and then promote the proliferation of killer immune cells to elicit tumor regression. We found that pHLIP-IL2 fusion proteins can be significantly enriched in tumor tissues and can effectively reduce tumor size in diverse tumor models, including breast cancer and melanoma, without apparent adverse effects. These data suggest that the pHLIP-IL2 fusion protein may be a promising solution for the continual and extensive application of IL-2, and pHLIP-IL2 is a potential and valuable therapeutic drug for cancer patients with antitumor immunotherapy.
AB - As a pleiotropic cytokine, interleukin-2 (IL-2) can effectively regulate lymphocyte proliferation, survival, and active antitumor immune responses in tumor microenvironments. Although the ability of IL-2 to boost immune responses was reported in cancer patients, its short circulating half-life and high toxicity hinder its broad and continual clinical application. Herein, we developed a novel tumor target agent by fusing pH low insertion peptides (pHLIP) with IL-2, forming the fusion protein pHLIP-IL2. Based on the low pH insertion property of pHLIP, the pHLIP-IL2 fusion protein could be selectively delivered to the acidic tumor microenvironments and then promote the proliferation of killer immune cells to elicit tumor regression. We found that pHLIP-IL2 fusion proteins can be significantly enriched in tumor tissues and can effectively reduce tumor size in diverse tumor models, including breast cancer and melanoma, without apparent adverse effects. These data suggest that the pHLIP-IL2 fusion protein may be a promising solution for the continual and extensive application of IL-2, and pHLIP-IL2 is a potential and valuable therapeutic drug for cancer patients with antitumor immunotherapy.
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U2 - 10.1021/acs.bioconjchem.3c00401
DO - 10.1021/acs.bioconjchem.3c00401
M3 - Article
C2 - 37787935
AN - SCOPUS:85174750142
SN - 1043-1802
VL - 34
SP - 1894
EP - 1901
JO - Bioconjugate chemistry
JF - Bioconjugate chemistry
IS - 10
ER -