# IMM2510, a novel anti-PD-L1/VEGF bispecific antibody for cancer immunotherapy

## TL;DR

IMM2510 is a new bispecific antibody that targets both PD-L1 and VEGF, showing strong preclinical results in fighting various cancers.

## Contribution

IMM2510 is a novel PD-L1×VEGF bispecific antibody with enhanced Fc-mediated effector functions and cooperative binding.

## Key findings

- IMM2510 effectively blocks PD-1/PD-L1 and VEGF/VEGFR interactions with high affinity.
- It induces potent ADCC and ADCP, and shows superior antitumor efficacy compared to monotherapies.
- Preclinical results demonstrate consistent efficacy across multiple tumor types including NSCLC and TNBC.

## Abstract

Dual inhibition of PD-1/PD-L1 and VEGF/VEGFR pathways is a promising strategy to overcome tumor immune evasion and inhibit angiogenesis. IMM2510 is a novel PD-L1 × VEGF bispecific antibody, constructed by fusing VEGFR1 domain 2 (VEGFR1D2) to each anti-PD-L1 heavy chain. In addition, IMM2510 incorporates an Fc region engineered for enhanced antibody-dependent cellular cytotoxicity (ADCC), enabling elimination of PD-L1-expressing tumor and stromal cells.

Binding and blocking activities were assessed using enzyme-linked immunosorbent assay, surface plasmon resonance, and flow cytometry. Functional assays included Jurkat-PD-1 and VEGFR2 reporter systems, HUVEC proliferation, mixed lymphocyte reaction, and NK cell-mediated cytotoxicity. Cooperative binding with VEGF165 was evaluated biochemically and in reporter assays. Antitumor efficacy was tested in MC38-hPD-L1 syngeneic tumors, HCC827 non-small cell lung cancer (NSCLC) xenografts, and MDA-MB-231 triple-negative breast cancer (TNBC) xenografts.

IMM2510 bound PD-L1, VEGF-A, VEGF-B, and PlGF with high affinity, and blocked both PD-1/PD-L1 and VEGF/VEGFR interactions. It reversed PD-1-mediated T-cell inhibition, inhibited VEGF-driven endothelial proliferation, and induced potent ADCC and ADCP in killing PD-L1+ tumor cells. Preincubation with VEGF165 enhanced PD-L1 binding and checkpoint blockade activity, indicating cooperative binding. In vivo, IMM2510 induced dose-dependent tumor growth inhibition, achieving superior efficacy to parental monotherapies and their combination. Consistent efficacy was observed across multiple tumor types, including NSCLC and TNBC.

IMM2510 combines checkpoint blockade, anti-angiogenesis, Fc-mediated effector function, and cooperative binding, resulting in superior preclinical antitumor activity across diverse tumor settings. These findings position IMM2510 as a differentiated next-generation therapeutic candidate for clinical development.

Statement of Significance MM2510 is an Fc-engineered PD-L1 × VEGF bispecific antibody in which each anti-PD-L1 heavy chain is fused to VEGFR1 domain 2. Preclinical studies have characterized the binding, functional activity, and antitumor efficacy, thus supporting it as a promising next-generation therapeutic candidate with broad potential in solid tumors.