VEGFR2-targeted fusion antibody improved NK cell-mediated immunosurveillance against K562 cells

Ren, Xueyan; Xie, Wei; Wang, Youfu; Xu, Menghuai; Liu, Fang; Tang, Mingxi; Li, Chenchen; Wang, Min; Zhang, Juan

doi:10.1007/s12026-016-8800-3

Cited by 4 publications

(5 citation statements)

References 38 publications

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“…The upregulated expression of PD-L1 was not associated with EGFR/STAT3 signaling pathway, but may be affected by EGFR/PI3K/AKT, EGFR/RAS/RAF/ERK, and EGR/PLC-γ signaling pathways [60]. VEGFR2-targeted fusion antibody improved NK cell-mediated immunosurveillance against K562 cells through increasing degranulation and cytokine production of NK cells [61].…”

Section: Effective Immunocyte Exclusion and Dysfunctionmentioning

confidence: 99%

Tumor-intrinsic signaling pathways: key roles in the regulation of the immunosuppressive tumor microenvironment

et al. 2019

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Immunotherapy is a currently popular treatment strategy for cancer patients. Although recent developments in cancer immunotherapy have had significant clinical impact, only a subset of patients exhibits clinical response. Therefore, understanding the molecular mechanisms of immunotherapy resistance is necessary. The mechanisms of immune escape appear to consist of two distinct tumor characteristics: a decrease in effective immunocyte infiltration and function and the accumulation of immunosuppressive cells in the tumor microenvironment. Several host-derived factors may also contribute to immune escape. Moreover, inter-patient heterogeneity predominantly results from differences in somatic mutations between cancers, which has led to the hypothesis that differential activation of specific tumor-intrinsic pathways may explain the phenomenon of immune exclusion in a subset of cancers. Increasing evidence has also shown that tumor-intrinsic signaling plays a key role in regulating the immunosuppressive tumor microenvironment and tumor immune escape. Therefore, understanding the mechanisms underlying immune avoidance mediated by tumor-intrinsic signaling may help identify new therapeutic targets for expanding the efficacy of cancer immunotherapies.

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Section: Effective Immunocyte Exclusion and Dysfunctionmentioning

confidence: 99%

Tumor-intrinsic signaling pathways: key roles in the regulation of the immunosuppressive tumor microenvironment

et al. 2019

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“…Our earlier studies had shown that anti-VEGFR2 exhibits an antitumor effect in breast cancer and leukemia. 29,30 We now extend these studies and show that anti-VEGFR2-IFNa2 (JZA01) has therapeutic efficacy both in vivo and in vitro against metastatic colorectal cancer.…”

Section: Introductionmentioning

confidence: 74%

Anti-VEGFR2-interferon-α2 regulates the tumor microenvironment and exhibits potent antitumor efficacy against colorectal cancer

Zhu

et al. 2017

OncoImmunology

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Interferon-α (IFNα) has multiple antitumor effects including direct antitumor toxicity and the ability to potently stimulate both innate and adaptive immunity. However, its clinical applications in the treatment of malignancies have been limited because of short half-life and serious adverse reactions when attempting to deliver therapeutically effective doses. To address these issues, we fused IFNα2a to the anti-vascular endothelial growth factor and receptor 2 (VEGFR2) antibody JZA00 with the goal of targeting it to the tumor microenvironment where it can stimulate the antitumor immune response. The fusion protein, JZA01, is effective against colorectal cancer by inhibiting angiogenesis, exhibiting direct cytotoxicity, and activating the antitumor immune response. Although JZA01 exhibited reduced IFNα2 activity compared with native IFNα2, VEGFR2 targeting permitted efficient antiproliferative, proapoptotic, antiangiogenesis, and immune-stimulating effects against the colorectal tumors HCT-116 and SW620. JZA01 showed efficacy in NOD-SCID mice-bearing established HCT-116 tumors. In conclusion, this study describes an antitumor immunotherapy that is highly promising for the treatment of colorectal cancer.

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“…Angiogenesis is critical for tumor growth and metastasis. VEGF/VEGFR signaling plays an important role in tumor growth, progression, metastasis, angiogenesis, and in tumor microenvironment, including immunosuppression (6,(16)(17)(18)(19)(20). Anti-angiogenic therapy targeting VEGF/VEGFR could transform the TME into an immunological favorable state, also described as a "hot" microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous high PD-L1 and low VEGFR2 expression is associated with better overall survival in rectal cancer

Ding¹,

Fu²,

Wei³

et al. 2021

Transl Cancer Res TCR

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Background:The aim of the present study was to analyze the association of programmed cell deathligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR2) expression levels with clinicopathological characteristics and survival to provide a treatment strategy for rectal cancer. Methods: Immunohistochemical staining of VEGFR2 and PD-L1 was carried out, and the association of PD-L1 and VEGFR2 expression levels with clinicopathological characteristics and survival were investigated in 77 pair-matched rectal cancer patients. Results: PD-L1 and VEGFR2 expression levels in surgical tumor tissues were higher than those in paired adjacent normal tissues, respectively (both P<0.05). The results of the 5-year overall survival (OS) analysis showed that patients with low VEGFR2 expression (66.7% vs. 43.5%, P=0.042) and high tumor PD-L1 expression (63.9% vs. 26.1%, P=0.001) in tumor tissues demonstrated significantly better OS. Patients with high TNM stage had poorer OS [hazard ratio (HR): 2.093, 95% confidence interval (CI): 1.027-4.087, P=0.030]. Similar results of poorer OS could be seen in patients with low tumor PD-L1 expression (HR:3.365, 95% CI:1.747-6.481, P=0.005), as well as patients with high tumor VEGFR2 expression (HR: 0.418, 95% CI: 0.232-0.993, P=0.048). Conclusions:The results indicated that tumor PD-L1 and VEGFR2 expression levels were associated with OS, and the combination of tumor PD-L1 and VEGFR2 levels might be an independent prognostic factor in rectal cancer.

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VEGFR2-targeted fusion antibody improved NK cell-mediated immunosurveillance against K562 cells

Cited by 4 publications

References 38 publications

Tumor-intrinsic signaling pathways: key roles in the regulation of the immunosuppressive tumor microenvironment

Tumor-intrinsic signaling pathways: key roles in the regulation of the immunosuppressive tumor microenvironment

Anti-VEGFR2-interferon-α2 regulates the tumor microenvironment and exhibits potent antitumor efficacy against colorectal cancer

Simultaneous high PD-L1 and low VEGFR2 expression is associated with better overall survival in rectal cancer

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