AUTHOR=Shi Fan , Yang Luying , Gao Ye , Hou Yan , Lv Qianxin , Cao Feng , Chen Xi , Zhang Jianying , Wang Le 

TITLE=Unlocking new horizons in oncology: ivonescimab’s dual-target approach to anti-VEGF/PD-1(L1) therapy

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1599181

DOI=10.3389/fimmu.2025.1599181

ISSN=1664-3224

ABSTRACT=Dual blockade of the PD-1/PD-L1 axis, enabling tumor immune evasion, and the VEGF pathway, driving immunosuppression, represents a promising cancer immunotherapy strategy. Combining immune checkpoint inhibitors (ICIs) with antiangiogenics faces toxicity and cost limitations. Bispecific antibodies (BsAbs) targeting both pathways offer a solution. Preclinical and clinical studies demonstrate that simultaneous inhibition enhances antitumor immunity by reversing T-cell exhaustion, normalizing vasculature, and countering immunosuppression. Ivonescimab, a first-in-class PD-1/VEGF BsAb, exemplifies this approach. Approved in China (NMPA, May 2024) for EGFR-mutant non-squamous NSCLC post-TKI failure and included in national insurance (November 2024), it is under global evaluation in solid tumors. PD-1(L1)/VEGF BsAbs like ivonescimab represent a novel therapeutic strategy with potential for improved efficacy and mitigated toxicity compared to combination therapies. Ongoing trials will define broader applications.