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

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.

KEYWORDS:

• Angiogenesis
• combination immunotherapy
• immune checkpoint inhibitor
• PB101
• PlGF
• tumor immunity
• VEGF-A

Disclosure statement

CK and HJC has received research grants from Panolos Bioscience. HGY, JAS, and HSL are full-time employees of Panolos Bioscience. The other authors have no potential conflicts of interest to disclose.

Author contributions

Study concept and design: EJG, HY, HGY, HSL, HJC, CK. Data curation and formal analysis: EJG, HY, SJL, WSL, HJC, CK. Investigation and data interpretation: All authors. Manuscript preparation: EJG, HY, SJL, HJC, CK. Approved the final manuscript: All authors.

Availability of data and materials

The dataset analyzed during the current study is available from the corresponding author on reasonable request.

Ethics approval

All mouse experiments were approved by the Institutional Animal Care and Use Committee (IACUC, #230015) of CHA University.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2023.2259212

Additional information

Funding

This work was supported by the National Research Foundation of Korea [NRF] grants funded by the Korean government [MSIT] [NRF-2023R1A2C2006375 to CK and NRF-2023R1A2C2004339 to HJC]. This work was supported by Panolos Bioscience, Inc.