Enhanced efficacy of combined VEGFR peptide–drug conjugate and anti-PD-1 antibody in treating hepatocellular carcinoma
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 VEGF 125 − 136 (QR) was conjugated with a lyti...
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Veröffentlicht in: | Scientific reports 2024-09, Vol.14 (1), p.21728-15, Article 21728 |
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Sprache: | eng |
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Zusammenfassung: | 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 VEGF
125 − 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. |
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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-024-72907-w |