Conditionally Active CD28xVISTA Bispecific Antibodies Promote Myeloid‑Driven T‑Cell Activation

Thomas Thisted
Sensei Biotherapeutics
September 19, 2025
Cancer Immunol Res
https://pubmed.ncbi.nlm.nih.gov/40970894/

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

https://pubmed.ncbi.nlm.nih.gov/40970894/

Research summary

The authors engineered pH‑selective CD28×VISTA bispecific antibodies (bsAbs) that engage VISTA on myeloid cells preferentially under acidic tumor microenvironment conditions, co‑stimulating CD28 on T cells only in tumors. In a humanized CD28 syngeneic mouse model, these bispecifics suppressed growth of VISTA‑expressing MC38 tumors, particularly in combination with anti‑PD‑1 therapy.

Key outcome of the study

The bsAb provided tumor-specific CD28 co‑stimulation in the TME, drove T cell activation, controlled tumor growth, and avoided systemic T‑cell activation / cytokine release in peripheral tissues

Model

Humanized CD28 Knockin mouse (syngeneic immunocompetent background, expressing human CD28) — genOway-developed

TARGET:
Cd28, Vsir (VISTA)
Synonyms:
CD28: — , VISTA: VSIR, B7-H5, PD‑1H

Keywords

Cancer immunotherapy, Tumor‑targeted costimulation, Bispecific antibodies, CD28 agonism, VISTA targeting, Myeloid‑mediated activation

Technical specifications

Human CD28 gene Knockin (replacing murine CD28), syngeneic tumor implantation (MC38 engineered to express human VISTA), pH‑sensitive binding engineering, in vivo treatment with bsAb ± anti‑PD‑1, T cell activation assays, cytokine panels

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