NI-3201 Is a Bispecific Antibody Mediating PD-L1-Dependent CD28 Co-stimulation on T Cells for Enhanced Tumor Control

Sara Majocchi
Light Chain Bioscience
January 6, 2025
Cancer Immunol Res
https://pubmed.ncbi.nlm.nih.gov/39760515/

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/39760515/

Research summary

This study reports the development and preclinical characterization of NI-3201, a PD-L1×CD28 bispecific antibody designed to promote T-cell activity and antitumor function through a dual mechanism of action: blocking the PD-L1/PD-1 immune checkpoint pathway and conditionally providing T-cell co-stimulation via CD28 when engaging PD-L1+ tumors or immune cells.

Key outcome of the study

NI-3201 enhances T-cell effector functionality in vitro and induces tumor regression and immunologic memory in vivo. It shows synergistic T cell–dependent cytotoxicity when combined with T-cell engagers and exhibits favorable tolerability and pharmacokinetics in nonhuman primates.

Model

Humanized PD-L1 and CD28 transgenic mouse models developed by genOway, expressing human PD-L1 and CD28 to evaluate the in vivo efficacy and safety of NI-3201.

TARGET:
CD274 (PD-L1), CD28
Synonyms:
B7-H1 (PD-L1), T44 (CD28)

Keywords

Cancer immunotherapy, Bispecific antibodies, PD-L1 blockade, CD28 co-stimulation, T-cell activation

Technical specifications

Humanized PD-L1 and CD28 transgenic mouse models, κλ-body platform, Immunocompetent syngeneic models, Pharmacokinetic and safety assessments

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The genO‑hCD28 mouse enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint CD28 in fully immunocompetent mice.

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