PB101, a VEGF- and PlGF-targeting decoy protein, enhances antitumor immunity and suppresses tumor progression and metastasis.

IF 7.2 2区 医学 Oncoimmunology Pub Date : 2023-09-20 eCollection Date: 2023-01-01 DOI:10.1080/2162402X.2023.2259212
Eun-Jin Go, Hannah Yang, Seung Joon Lee, Hyun Gul Yang, Jin A Shin, Won Suk Lee, Hye Seong Lim, Hong Jae Chon, Chan Kim
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Abstract

Antiangiogenic therapy is a recognized method for countering the immunosuppressive tumor microenvironment (TME) and improving anti-tumor immunity. PB101 is a glycosylated decoy receptor that binds to VEGF-A and PlGF with high affinity, based on the VEGFR1 backbone. Here, we elucidated PB101-induced remodeling of tumor angiogenesis and immunity, which enhances anti-PD-L1 immune checkpoint blockade. PB101 inhibited tumor growth by suppressing angiogenesis and enhancing CD8+ T cell infiltration into the tumors. PB101 induced robust reprogramming of antitumor immunity and activates intratumoral CD8+ T cells. Anti-tumor efficacy of PB101 is mostly dependent on CD8+ T cells and IFN-γ. PB101 reprograms tumor immunity in a manner distinct from that of the conventional VEGF decoy receptor, VEGF-trap. With its potent immune-modulating capability, PB101 synergizes with an anti-PD-L1, triggering strengthened antitumor immunity. Combining PB101 and anti-PD-L1 could establish durable protective immunity against tumor recurrence and metastasis. The findings of this study offer scientific rationales for further clinical development of PB101, particularly when used in combination with immune checkpoint inhibitors, as a potential treatment for advanced cancers.

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PB101是一种靶向VEGF和PlGF的诱饵蛋白,可增强抗肿瘤免疫并抑制肿瘤进展和转移。
抗血管生成疗法是对抗免疫抑制肿瘤微环境(TME)和提高抗肿瘤免疫力的公认方法。PB101是一种基于VEGFR1骨架的糖基化诱饵受体,以高亲和力结合VEGF-a和PlGF。在这里,我们阐明了PB101诱导的肿瘤血管生成和免疫的重塑,它增强了抗PD-L1免疫检查点阻断。PB101通过抑制血管生成和增强CD8+T细胞向肿瘤的浸润来抑制肿瘤生长。PB101诱导抗肿瘤免疫的强大重编程,并激活肿瘤内CD8+T细胞。PB101的抗肿瘤作用主要依赖于CD8+T细胞和IFN-γ。PB101以不同于常规VEGF诱饵受体VEGF陷阱的方式重新编程肿瘤免疫。PB101具有强大的免疫调节能力,与抗PD-L1协同作用,引发增强的抗肿瘤免疫。结合PB101和抗PD-L1可以建立持久的抗肿瘤复发和转移的保护性免疫。这项研究的发现为PB101的进一步临床开发提供了科学依据,特别是当与免疫检查点抑制剂联合使用时,作为晚期癌症的潜在治疗方法。
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来源期刊
Oncoimmunology
Oncoimmunology ONCOLOGY-IMMUNOLOGY
CiteScore
12.80
自引率
2.80%
发文量
276
期刊介绍: Tumor immunology explores the natural and therapy-induced recognition of cancers, along with the complex interplay between oncogenesis, inflammation, and immunosurveillance. In response to recent advancements, a new journal, OncoImmunology, is being launched to specifically address tumor immunology. The field has seen significant progress with the clinical demonstration and FDA approval of anticancer immunotherapies. There's also growing evidence suggesting that many current chemotherapeutic agents rely on immune effectors for their efficacy. While oncologists have historically utilized chemotherapeutic and radiotherapeutic regimens successfully, they may have unwittingly leveraged the immune system's ability to recognize tumor-specific antigens and control cancer growth. Consequently, immunological biomarkers are increasingly crucial for cancer prognosis and predicting chemotherapy efficacy. There's strong support for combining conventional anticancer therapies with immunotherapies. OncoImmunology will welcome high-profile submissions spanning fundamental, translational, and clinical aspects of tumor immunology, including solid and hematological cancers, inflammation, and both innate and acquired immune responses.
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