1. Enhanced efficacy of combined VEGFR peptide–drug conjugate and anti-PD-1 antibody in treating hepatocellular carcinoma
- Author
-
Jiacheng Liu, Yaowei Bai, Xiaoming Liu, Binqian Zhou, Peng Sun, Yingliang Wang, Shuguang Ju, Chen Zhou, Chaoyang Wang, Wei Yao, Huihui Yang, Xin Jiang, Lian Yang, Dongyuan Wang, and Chuansheng Zheng
- Subjects
Angiogenesis ,anti-PD-1 antibody ,Peptide–drug conjugate ,Tumor burden ,Tumor vascular normalization ,Medicine ,Science - Abstract
Abstract This study aimed to design a VEGFR-targeting peptide–drug conjugate with the ability to decrease tumor burden and suppress tumor angiogenesis, and to further evaluate the therapeutic effect of anti-PD-1 antibody in HCC therapy. A VEGFR-targeting peptide VEGF125 − 136 (QR) was conjugated with a lytic peptide (KLU) to form a peptide–drug conjugate QR-KLU. And the efficacy of QR-KLU in combination with anti-PD-1 antibody for HCC therapy in vivo and in vitro were evaluated. QR-KLU inhibited the proliferation and migration of mouse HCC cell line (Hepa1–6) cells under normoxic and hypoxic conditions in a dose-dependent manner. In the subcutaneous Hepa1–6 tumor model, QR-KLU combined with the anti-PD-1 antibody substantially inhibited tumor growth, promoted tumor necrosis, and prolonged the survival time of tumor-bearing mice. QR-KLU substantially inhibited hypoxia-induced expression of VEGF, promoted tumor vascular normalization, and increased cluster of differentiation 8+ (CD8+) T cell infiltration in the tumor. In addition, QR-KLU and anti-PD-1 antibody demonstrated a strong synergistic effect in promoting the activation of intratumoral CD8+ T cells, reducing the expression of immune-inhibitory factors, and increasing the expression of immune-stimulatory factors. This study proposed a novel approach for enhancing the efficacy of anti-PD-1 antibody using a VEGFR-targeting peptide–drug conjugate in HCC therapy.
- Published
- 2024
- Full Text
- View/download PDF