PMID- 35798286 OWN - NLM STAT- MEDLINE DCOM- 20220809 LR - 20220818 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 182 DP - 2022 Aug TI - A PD-L1 and VEGFR2 dual targeted peptide and its combination with irradiation for cancer immunotherapy. PG - 106343 LID - S1043-6618(22)00288-2 [pii] LID - 10.1016/j.phrs.2022.106343 [doi] AB - Although the blockade of immune checkpoint PD-1/PD-L1 has achieved great success, the lack of tumor-infiltrating immune cells and PD-L1 expression in the tumor microenvironment results in a limited response in certain tumor types. Thus, rational and optimal combination strategies were urgently needed. The combination of PD-1/PD-L1 blockade and anti-angiogenic therapy has been reported to have great potential. Here, a chimeric peptide OGS was designed by conjugating the peptides OPBP-1 (8-12) and (D)A7R targeting PD-L1 and VEGFR2, respectively. OGS could bind to both human and mouse PD-L1 with high affinity and block the PD-1/PD-L1 interaction, and also inhibit the migration and tube formation of HUVEC cells in wound healing and tube formation assays. To further prolong the half-life of OGS, it was modified by coupling with peptide (D)SP which has a high binding affinity to both human serum albumin (HSA) and mouse serum albumin (MSA) to form the peptide (D)SPOGS. (D)SPOGS could not directly affect the viability, apoptosis, and cell cycle of tumor cells in vitro, while significantly inhibiting the tumor growth in the MC38 mouse model. (D)SPOGS could elicit a potent anti-tumor immune response and inhibit tumor angiogenesis, with the enhancement of tumor infiltrating CD8(+) T cells and the IFN-gamma secreting CD8(+) T cells in the spleen and tumor-draining lymph node. Further, the combination of radiotherapy with (D)SPOGS could dramatically improve the therapeutic efficacy. Our study could provide a promising paradigm for the combination of immune checkpoint blockade, anti-angiogenesis, and radiotherapy. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Jiao, Ling AU - Jiao L AD - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China. FAU - Dong, Qingyu AU - Dong Q AD - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China. FAU - Zhai, Wenjie AU - Zhai W AD - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China. FAU - Zhao, Wenshan AU - Zhao W AD - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China. FAU - Shi, Peishang AU - Shi P AD - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China. FAU - Wu, Yahong AU - Wu Y AD - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China. FAU - Zhou, Xiuman AU - Zhou X AD - School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China. Electronic address: zhouxm36@mail.sysu.edu.cn. FAU - Gao, Yanfeng AU - Gao Y AD - School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China. Electronic address: gaoyf29@mail.sysu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220704 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (B7-H1 Antigen) RN - 0 (Peptides) RN - 0 (Programmed Cell Death 1 Receptor) RN - EC 2.7.10.1 (KDR protein, human) RN - EC 2.7.10.1 (Kdr protein, mouse) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2) SB - IM MH - Animals MH - *B7-H1 Antigen/metabolism MH - CD8-Positive T-Lymphocytes MH - Cell Line, Tumor MH - Humans MH - Immunotherapy/methods MH - Mice MH - *Neoplasms/drug therapy/radiotherapy MH - Peptides/pharmacology/therapeutic use MH - Programmed Cell Death 1 Receptor/metabolism MH - Tumor Microenvironment MH - Vascular Endothelial Growth Factor Receptor-2/*metabolism OTO - NOTNLM OT - Albumin binding peptide OT - Angiogenesis OT - Cancer immunotherapy OT - PD-1/PD-L1 OT - Radiotherapy EDAT- 2022/07/08 06:00 MHDA- 2022/08/10 06:00 CRDT- 2022/07/07 19:33 PHST- 2022/01/08 00:00 [received] PHST- 2022/06/03 00:00 [revised] PHST- 2022/07/01 00:00 [accepted] PHST- 2022/07/08 06:00 [pubmed] PHST- 2022/08/10 06:00 [medline] PHST- 2022/07/07 19:33 [entrez] AID - S1043-6618(22)00288-2 [pii] AID - 10.1016/j.phrs.2022.106343 [doi] PST - ppublish SO - Pharmacol Res. 2022 Aug;182:106343. doi: 10.1016/j.phrs.2022.106343. Epub 2022 Jul 4.